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Study of Gemcitabine + PEGPH20 vs Gemcitabine Alone in Stage IV Previously Untreated Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01453153
Recruitment Status : Completed
First Posted : October 17, 2011
Results First Posted : November 30, 2018
Last Update Posted : November 30, 2018
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Stage IV Pancreatic Cancer
Interventions Drug: Gemcitabine
Drug: PEGPH20
Drug: Placebo
Enrollment 28
Recruitment Details  
Pre-assignment Details This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20).
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Period Title: Overall Study
Started 4 4 20
Completed 0 0 0
Not Completed 4 4 20
Reason Not Completed
Physician Decision             0             0             1
Progressive Disease             3             2             16
Withdrawal by Subject             0             1             2
Adverse Event             1             1             1
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg Total
Hide Arm/Group Description Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Total of all reporting groups
Overall Number of Baseline Participants 4 4 20 28
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 4 participants 20 participants 28 participants
50.5  (8.06) 59.0  (8.72) 60.3  (13.50) 58.7  (12.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 20 participants 28 participants
Female
2
  50.0%
2
  50.0%
10
  50.0%
14
  50.0%
Male
2
  50.0%
2
  50.0%
10
  50.0%
14
  50.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 4 participants 20 participants 28 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
  25.0%
0
   0.0%
2
  10.0%
3
  10.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
3
  75.0%
4
 100.0%
18
  90.0%
25
  89.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Number of Participants With a Dose-limiting Toxicity (DLT)
Hide Description The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by measuring the number of participants with a DLT during the dose-escalation phase of the study. A DLT was defined as any treatment-emergent National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE), Version 4.0, Grade 3 or greater event occurring within the first 4 weeks of treatment that was considered related to PEGPH20. Any PEGPH20 treatment-related AE that resulted in a drug interruption or reduction might have been considered a DLT at the Investigator's or Sponsor's discretion. Hypersensitivity/infusion reactions related to PEGPH20 dosing were not considered DLTs.
Time Frame first 4 weeks of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The DLT Evaluable Population: all participants enrolled during the dose escalation portion of the study who received at least 6 of 8 planned doses of PEGPH20 and 3 of 4 doses of gemcitabine in the first 4 weeks or had a DLT in the first 4 weeks.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title Recommended Phase 2 Dose (RP2D)
Hide Description The safety and tolerability profile of PEGPH20 used in combination with gemcitabine was assessed by determining the RP2D, the highest dose level at which no more than 1 of 6 evaluable participants experienced a DLT in the first 4 weeks of treatment (considered a safe dose). The RP2D was determined based on review of safety and pharmacokinetic (PK) data from participants enrolled during the dose-escalation phase of the study.
Time Frame first 4 weeks of Cycle 1
Hide Outcome Measure Data
Hide Analysis Population Description
The DLT Evaluable Population: all participants enrolled during the dose escalation portion of the study who received at least 6 of 8 planned doses of PEGPH20 and 3 of 4 doses of gemcitabine in the first 4 weeks or had a DLT in the first 4 weeks
Arm/Group Title PEGPH20 Plus Gemcitabine
Hide Arm/Group Description:
Participants received PEGPH20 1.0, 1.6, and 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. Participants received dexamethasone 4 or 8 mg orally, via intramuscular injection, or via IV injection. Dexamethasone (4 to 8 mg) was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 14
Measure Type: Number
Unit of Measure: micrograms per kilogram (μg/kg)
3.0
3.Secondary Outcome
Title Observed Maximum Plasma Concentration (Cmax) Following Single PEGPH20 Doses
Hide Description Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment.
Time Frame Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all enrolled participants
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Mean (Standard Deviation)
Unit of Measure: units per milliliter
0.604  (0.438) 1.54  (0.491) 3.18  (1.28)
4.Secondary Outcome
Title Cmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Hide Description Cmax is defined as the observed maximum plasma concentration after the first dose. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Time Frame Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population: all enrolled participants. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 4 12
Mean (Standard Deviation)
Unit of Measure: units per milliliter
1.08  (0.0878) 2.40  (0.542) 3.98  (1.16)
5.Secondary Outcome
Title Last Measurable Observed Plasma Concentration (Cmin) Following Single PEGPH20 Doses
Hide Description Blood samples were collected for pharmacokinetic assessment.
Time Frame Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 4 20
Mean (Standard Deviation)
Unit of Measure: units per milliliter
0.626  (0.0607) 0.651  (0.155) 0.864  (0.375)
6.Secondary Outcome
Title Cmin Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Hide Description Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Time Frame Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 4 12
Mean (Standard Deviation)
Unit of Measure: Units per milliliter
0.572  (0.0781) 0.976  (0.568) 1.52  (0.767)
7.Secondary Outcome
Title Time to Reach Cmax (Tmax) Following Single PEGPH20 Doses
Hide Description Blood samples were collected for pharmacokinetic assessment.
Time Frame Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 4 20
Median (Full Range)
Unit of Measure: hours
0.250
(0.180 to 0.330)
0.250
(0.250 to 1.15)
0.420
(0.330 to 2.17)
8.Secondary Outcome
Title Tmax Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Hide Description Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional.
Time Frame Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 4 12
Median (Full Range)
Unit of Measure: hours
0.330
(0.320 to 0.330)
0.325
(0.250 to 2.08)
0.420
(0.420 to 2.15)
9.Secondary Outcome
Title Apparent Half-life (t1/2) Following Single PEGPH20 Doses
Hide Description The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. t1/2 is expressed as harmonic mean and pseudo standard deviation.
Time Frame Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed. t1/2 values were not calculated for the 1.0 μg/kg dose because there were insufficient data points in the profiles due to low concentrations.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 0 2 18
Mean (Standard Deviation)
Unit of Measure: hours
18.6  (0.255) 8.24  (8.03)
10.Secondary Outcome
Title t1/2 Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Hide Description The apparent half-life calculated by ln(2)/λ, where λ was the rate constant for the log-linear portion of the terminal phase. A minimum of 3 values in the postdistribution phase of the plasma concentration-time curve were required for calculation of λ. Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. t1/2 is expressed as harmonic mean and pseudo standard deviation.
Time Frame Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 2 9
Mean (Standard Deviation)
Unit of Measure: hours
5.60  (3.08) 19.5  (7.75) 10.7  (4.06)
11.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Measurable Plasma Concentration (AUC0-T) Following Single PEGPH20 Doses
Hide Description Blood samples were collected for pharmacokinetic assessment. AUC0-T was calculated by the linear trapezoidal rule.
Time Frame Cycle 1, Week 1, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Mean (Standard Deviation)
Unit of Measure: Units*hour/milliliter
1.39  (1.57) 13.6  (11.8) 31.5  (18.0)
12.Secondary Outcome
Title AUC0-T Following Twice-weekly PEGPH20 Doses for 3 Consecutive Weeks
Hide Description Blood samples were collected for pharmacokinetic assessment. The 24-hour sample collected at the first visit was optional. AUC0-T was calculated by the linear trapezoidal rule.
Time Frame Cycle 1, Week 4, Day 1: First visit: predose; 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing; all other visits: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 4 12
Mean (Standard Deviation)
Unit of Measure: Units*hour/milliliter
2.99  (0.607) 21.5  (11.9) 35.2  (23.5)
13.Secondary Outcome
Title Plasma Hyaluronan (HA) Concentration at Baseline and After PEGPH20 Administration
Hide Description The pharmacodynamic activity of PEGPH20 was evaluated by measuring plasma concentrations of HA after PEGPH20 dosing. Peak HA concentrations are the highest concentrations measured after a single dose of PEGPH20. HA samples were collected in Cycle 1 at the following time points: 1) Week 1/Day 1 (first visit) and Week 4 (first visit): predose and 15 minutes, 1, 2, 4, and 24 hours post-PEGPH20 dosing (24-hour sample optional for Week 4); 2) all other visits in Cycle 1: pre-PEGPH20 dose, 1 to 2 hours post-PEGPH20 dose, and immediately after the dose of gemcitabine (on the days gemcitabine was given). HA samples were collected in Cycles 2+ at the following time points: Week 3 of each cycle pre-PEGPH20 dose and 1 to 2 hours post-PEGPH20 dose.
Time Frame Baseline; post-Baseline (average treatment duration of 94.6 days)
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Hide Analysis Population Description
Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter
Baseline 123.7  (137.6) 982.3  (1370) 164.7  (139.6)
After PEGPH20 administration 7288  (10027) 27818  (25866) 128411  (126357)
14.Secondary Outcome
Title H-scores, as an Assessment of HA Staining Changes in Tumor Biopsies
Hide Description An H-score approach methodology was developed and used to analyze staining in the tumor pericellular regions and the stroma separately. The H-score calculation was the sum of the products of the percentage of positive staining areas and the staining intensity (0, 1, 2 or 3), and ranged from 0 to 300. For example: [90% * 1 (weak)] + [10% * 2 (moderate)] + [0% * 3 (strong)] = 110. A score of 0 represents the absence of expression, and an H-score of 300 represents maximum expression. A larger decrease in H-score correlated with a greater target engagement of PEGPH20. As HA is a secreted protein, the scoring was performed in the immediate areas surrounding tumor (pericellular areas) as well as in stroma.
Time Frame Screening; Cycle 1 Week 7
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only 1 participant had a screening and post-treatment specimen that qualified for staining. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 0 0 1
Measure Type: Number
Unit of Measure: score on a scale
Screening pericellular tumor H-score 40
Screening stromal H-score 260
Post-treatment pericellular tumor H-score 15
Post-treatment stromal tumor H-score 150
15.Secondary Outcome
Title Percent Change in in the Maximum Standardized Uptake Value (SUVmax), as an Assessment of Total Lesion Metabolic Activity
Hide Description PEGPH20's effect on the metabolic activities of the tumor was assessed as the percent change in SUVmax (a measure of total lesion metabolic activity) using fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). Assessment was done for the entire cohort of participants, not per treatment group.
Time Frame Baseline; up to 32 weeks for each individual participant (end of Cycle 7)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0, 1.6, or 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: percent change
Cycle 1 Number Analyzed 5 participants
-36.7  (19.2)
Cycle 3 Number Analyzed 4 participants
-43.2  (12.4)
Cycle 5 Number Analyzed 3 participants
-39.3  (20.6)
Cycle 7 Number Analyzed 2 participants
-41.2  (61.0)
16.Secondary Outcome
Title Mean Volume Transfer Constant (Ktrans) for Scans Across Tissue Sites
Hide Description Dynamic control enhanced-magnetic resonance imaging (DCE-MRI) provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Using a 2-compartment pharmacokinetic model, an estimate of tissue (tumor) perfusion can be obtained by determining the exchange rate constant (Ktrans) of contrast exchange. Ktrans is defined as the volume transfer constant between extravascular/extracellular space to plasma space and is a measure of blood flow, vascular permeability, or both. Mean Ktrans values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.
Time Frame Baseline; 24 hours hours; end of Cycle 1 (Week 7)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. DCE-MRI scans were performed for 6 participants. Only participants with data available were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0, 1.6, or 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: milliliters (mL) per minute per 100 mL
Participant 1, Baseline 0.124 [1]   (NA)
Participant 1, 24 hours 0.383 [1]   (NA)
Participant 1, End of Cycle 1 NA [2]   (NA)
Participant 2, Baseline 0.430 [1]   (NA)
Participant 2, 24 hours 0.468 [1]   (NA)
Participant 2, End of Cycle 1 NA [2]   (NA)
Participant 3, Baseline 0.402 [1]   (NA)
Participant 3, 24 hours 0.331 [1]   (NA)
Participant 3, End of Cycle 1 NA [2]   (NA)
Participant 4, Baseline 0.564 [1]   (NA)
Participant 4, 24 hours 0.672 [1]   (NA)
Participant 4, End of Cycle 1 0.646 [1]   (NA)
Participant 5, Baseline 0.135 [1]   (NA)
Participant 5, 24 hours 0.197 [1]   (NA)
Participant 5, End of Cycle 1 0.133 [1]   (NA)
Participant 6, Baseline 0.249 [1]   (NA)
Participant 6, 24 hours 0.376 [1]   (NA)
Participant 6, End of Cycle 1 0.078 [1]   (NA)
[1]
A standard deviation was not calculated for the mean values across scan sites for single participants.
[2]
A scan was not performed at this time point.
17.Secondary Outcome
Title Mean Extravascular-Extracellular Volume Fraction (Ve) for Scans Across Tissue Sites
Hide Description DCE-MRI provides a measure of the exchange of small-molecule contrast agents between the intracellular and extracellular spaces. Ve is defined as the extravascular-extracellular volume fraction and is a measure of extracellular, extravascular space. Mean Ve values across scan sites are reported per participant. DCE-MRI was performed before the first dosing visit (Week 1/Day 1), 24 hours after the first dose of PEGPH20 in Cycle 1, and 24 hours after the last dose of PEGPH20 in Cycle 1 (Week 7). Assessment was done for the entire cohort of participants, not per treatment group.
Time Frame Baseline; 24 hours hours; end of Cycle 1 (Week 7)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. DCE-MRI scans were performed for 6 participants. Only participants with data available were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0, 1.6, or 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: milliliters
Participant 1, Baseline 0.162 [1]   (NA)
Participant 1, 24 hours 0.327 [1]   (NA)
Participant 1, End of Cycle 1 NA [2]   (NA)
Participant 2, Baseline 0.671 [1]   (NA)
Participant 2, 24 hours 0.386 [1]   (NA)
Participant 2, End of Cycle 1 NA [2]   (NA)
Participant 3, Baseline 0.481 [1]   (NA)
Participant 3, 24 hours 0.389 [1]   (NA)
Participant 3, End of Cycle 1 NA [2]   (NA)
Participant 4, Baseline 0.458 [1]   (NA)
Participant 4, 24 hours 0.788 [1]   (NA)
Participant 4, End of Cycle 1 0.751 [1]   (NA)
Participant 5, Baseline 0.380 [1]   (NA)
Participant 5, 24 hours 0.395 [1]   (NA)
Participant 5, End of Cycle 1 0.550 [1]   (NA)
Participant 6, Baseline 0.355 [1]   (NA)
Participant 6, 24 hours 0.825 [1]   (NA)
Participant 6, End of Cycle 1 0.425 [1]   (NA)
[1]
A standard deviation was not calculated for the mean values across scan sites for single participants.
[2]
A scan was not performed at this time point.
18.Secondary Outcome
Title Number of Participants With the Indicated Best Response, Per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1
Hide Description Target lesions (TLs), complete response (CR): Disappearance of all TLs. Partial response (PR): >=30% decrease in the sum of diameters of TLs, referencing baseline sums. Progressive disease (PD): >= 20% increase in the sum of diameters of TLs, referencing the smallest sum (including baseline sum). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of >=5 mm. (The appearance of >=1 new lesions is considered progression.) Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For nontarget lesions (NTLs), CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits. PD: Unequivocal progression of existing NTLs. (The appearance of >=1 new lesions is considered progression.)
Time Frame up to approximately 2 years 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Measure Type: Count of Participants
Unit of Measure: Participants
CR
0
   0.0%
0
   0.0%
0
   0.0%
PR
0
   0.0%
2
  50.0%
8
  40.0%
SD
1
  25.0%
2
  50.0%
6
  30.0%
PD
3
  75.0%
0
   0.0%
0
   0.0%
Unknown
0
   0.0%
0
   0.0%
6
  30.0%
19.Secondary Outcome
Title Objective Response Rate
Hide Description Objective Response Rate is defined as the number of participants with a complete response plus the number of participants with a partial response, per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.
Time Frame up to approximately 2 years 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
2
  50.0%
8
  40.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PEGPH20 1.0 μg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 0
Confidence Interval (2-Sided) 95%
0 to 60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PEGPH20 1.6 μg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 50
Confidence Interval (2-Sided) 95%
7 to 93
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PEGPH20 3.0 μg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 40
Confidence Interval (2-Sided) 95%
19 to 64
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Disease Control Rate
Hide Description Disease Control Rate is defined as the sum of the number of participants with a complete response, the number of participants with a partial response, and the number of participants with stable disease per RECIST, Version 1.1. For TLs, CR: Disappearance of all TLs. PR: >=30% decrease in the sum of diameters of TLs, referencing baseline sums. SD: Neither sufficient shrinkage to qualify for PR nor sufficient to qualify for PD, referencing the smallest sum diameters. For NTLs, CR: Disappearance of all NTLs and normalization of tumor marker level. All lymph nodes must be nonpathological in size (short axis <10 mm). Incomplete response/SD: Persistence of >=1 NTLs and/or maintenance of tumor marker level above normal limits.
Time Frame up to approximately 2 years 4 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Measure Type: Count of Participants
Unit of Measure: Participants
1
  25.0%
4
 100.0%
14
  70.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PEGPH20 1.0 μg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 25
Confidence Interval (2-Sided) 95%
1 to 81
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection PEGPH20 1.6 μg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 100
Confidence Interval (2-Sided) 95%
40 to 100
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection PEGPH20 3.0 μg/kg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 70
Confidence Interval (2-Sided) 95%
46 to 88
Estimation Comments [Not Specified]
21.Secondary Outcome
Title Progression-free Survival (PFS)
Hide Description PFS duration was defined as the time from the first dose of PEGPH20 until objective tumor progression or death. Per RECIST, Version 1.1, for the evaluation of target lesions, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters. Note: the appearance of 1 or more new lesions is also considered progression. For the evaluation of nontarget lesions, progressive disease is defined as the unequivocal progression of existing nontarget lesions. Note: The appearance of 1 or more new lesions is also considered progression.
Time Frame from the first dose of PEGH20 until objective tumor progression or death (up to approximately 2 years 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Median (95% Confidence Interval)
Unit of Measure: days
47.0
(45.0 to 100.0)
276.0
(47.0 to 276.0)
113.0
(50.0 to 166.0)
22.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from the time of the first dose of PEGPH20 until death.
Time Frame from the time of the first dose of PEGPH20 until death (up to approximately 2 years 4 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Median (95% Confidence Interval)
Unit of Measure: days
109.5
(48.0 to 424.0)
199.5
(96.0 to 529.0)
220.0
(123.0 to 370.0)
23.Secondary Outcome
Title Change From Baseline in Carbohydrate Antigen 19-9 or Sialylated Lewis(a) Antigen (CA19-9)
Hide Description CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.
Time Frame up to the end of Cycle 10 (up to Week 44)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 4 4 20
Mean (Standard Deviation)
Unit of Measure: Units per milliliter (U/ml)
Cycle 1, Week 4, Visit 1 Number Analyzed 3 participants 3 participants 14 participants
12897.5  (22345.65) -7833.9  (13567.21) -11800.3  (38780.49)
Cycle 1, Week 8, Visit 1 Number Analyzed 1 participants 2 participants 13 participants
0.0 [1]   (NA) -1.9  (2.69) -15464.1  (41440.85)
Cycle 2, Week 4, Visit 1 Number Analyzed 1 participants 2 participants 10 participants
0.0 [1]   (NA) -1.2  (1.63) -16581.0  (50738.98)
Cycle 3, Week 4, Visit 1 Number Analyzed 0 participants 1 participants 8 participants
0.0 [1]   (NA) -12628.0  (72538.77)
Cycle 4, Week 4, Visit 1 Number Analyzed 0 participants 1 participants 8 participants
0.0 [1]   (NA) -24089.1  (54120.73)
Cycle 5, Week 4, Visit 1 Number Analyzed 0 participants 1 participants 6 participants
0.0 [1]   (NA) -27214.3  (64893.40)
Cycle 6, Week 4, Visit 1 Number Analyzed 0 participants 1 participants 3 participants
0.0 [1]   (NA) -53200.6  (88132.74)
Cycle 7, Week 4, Visit 1 Number Analyzed 0 participants 1 participants 1 participants
0.0 [1]   (NA) -154964 [1]   (NA)
Cycle 8, Week 4, Visit 1 Number Analyzed 0 participants 1 participants 1 participants
0.0 [1]   (NA) -154946 [1]   (NA)
Cycle 9, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 1 participants
-154940 [1]   (NA)
Cycle 10, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 1 participants
-154937 [1]   (NA)
[1]
The standard deviation cannot be calculated for a single participant.
24.Secondary Outcome
Title Change From Baseline in CA19-9 in Participants With a Baseline Value >=59 U/ml
Hide Description CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations.
Time Frame up to the end of Cycle 10 (up to Week 44)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 3 2 17
Mean (Standard Deviation)
Unit of Measure: U/ml
Cycle 1, Week 4, Visit 1 Number Analyzed 2 participants 1 participants 11 participants
19346.2  (27370.41) -23500.0 [1]   (NA) -15018.9  (43611.09)
Cycle 1, Week 8, Visit 1 Number Analyzed 0 participants 0 participants 11 participants
-18274.5  (44769.87)
Cycle 2, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 8 participants
-20724.4  (56673.61)
Cycle 3, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 6 participants
-16835.7  (85332.54)
Cycle 4, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 7 participants
-27530.1  (57504.01)
Cycle 5, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 5 participants
-32656.8  (71005.52)
Cycle 6, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 2 participants
-79800.9  (106251.1)
Cycle 7, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 1 participants
-154964 [1]   (NA)
Cycle 8, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 1 participants
-154946 [1]   (NA)
Cycle 9, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 1 participants
-154940 [1]   (NA)
Cycle 10, Week 4, Visit 1 Number Analyzed 0 participants 0 participants 1 participants
-154937 [1]   (NA)
[1]
The standard deviation cannot be calculated for a single participant.
25.Secondary Outcome
Title Change From Baseline in CA19-9 in Participants Classified as Responders and Non-responders
Hide Description CA19-9 is a tumor marker. Blood samples (plasma) were collected for CA19-9 evaluations. Responders are defined as participants who had a complete response or partial response, and non-responders are defined as participants who had stable disease, progressive disease, or an unknown tumor response, per RECIST, Version 1.1.
Time Frame up to the end of Cycle 10 (up to Week 44)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat Population. Only those participants with available data were analyzed. This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
Arm/Group Title Responders Non-responders
Hide Arm/Group Description:
Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0, 1.6, or 3.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Participants received PEGPH20 1.0, 1.6, or 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
Overall Number of Participants Analyzed 10 18
Mean (Standard Deviation)
Unit of Measure: U/ml
Cycle 1, Week 4, Visit 1 Number Analyzed 10 participants 10 participants
-15677.1  (45962.74) 675.7  (15184.14)
Cycle 1, Week 8, Visit 1 Number Analyzed 10 participants 6 participants
-16367.0  (47164.85) -6227.9  (12527.76)
Cycle 2, Week 4, Visit 1 Number Analyzed 8 participants 5 participants
-21587.2  (53784.34) 1377.1  (21979.93)
Cycle 3, Week 4, Visit 1 Number Analyzed 6 participants 3 participants
-28752.7  (61783.48) 23830.5  (78609.44)
Cycle 4, Week 4, Visit 1 Number Analyzed 8 participants 1 participants
-19976.6  (54603.40) -32900.0 [1]   (NA)
Cycle 5, Week 4, Visit 1 Number Analyzed 6 participants 1 participants
-22347.6  (65803.24) -29200.0 [1]   (NA)
Cycle 6, Week 4, Visit 1 Number Analyzed 4 participants 0 participants
-39900.5  (76719.16)
Cycle 7, Week 4, Visit 1 Number Analyzed 2 participants 0 participants
-77482.1  (109576.2)
Cycle 8, Week 4, Visit 1 Number Analyzed 2 participants 0 participants
-77472.8  (109563.0)
Cycle 9, Week 4, Visit 1 Number Analyzed 1 participants 0 participants
-154940 [1]   (NA)
Cycle 10, Week 4, Visit 1 Number Analyzed 1 participants 0 participants
-154937 [1]   (NA)
[1]
The standard deviation cannot be calculated for a single participant.
Time Frame [Not Specified]
Adverse Event Reporting Description This study was to consist of a Phase 1b and a randomized Phase 2 study. However, the randomized Phase 2 study was not conducted due to a change to the standard-of-care chemotherapy treatment to be used in combination with PEGPH20.
 
Arm/Group Title PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Hide Arm/Group Description Participants received PEGylated Recombinant Human Hyaluronidase PH20 (PEGPH20) 1.0 micrograms per kilogram (μg/kg). PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 milligrams per meters squared (mg/m^2) administered via intravenous (IV) infusion. Before the Recommend Phase 2 Dose (RP2D) was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Participants received PEGPH20 1.6 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing. Participants received PEGPH20 3.0 μg/kg. PEGPH20 was administered twice weekly for 4 consecutive weeks and then once weekly for the next 3 weeks during Cycle 1. For each cycle thereafter, PEGPH20 was administered once weekly for 3 consecutive weeks. Participants received gemcitabine 1000 mg/m^2 administered via IV infusion. Before the RP2D was established, gemcitabine was administered 2 hours after the second dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and on the same day as PEGPH20 during each week thereafter. After the RP2D was established, gemcitabine was administered within 24 hours after the first dose of PEGPH20 during Weeks 1 to 4 of Cycle 1 and 2 to 24 hours after each PEGPH20 dose thereafter. Dexamethasone was administered approximately 1 hour prior to and 8 to 12 hours after PEGPH20 dosing.
All-Cause Mortality
PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   4/4 (100.00%)   17/20 (85.00%) 
Hide Serious Adverse Events
PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/4 (50.00%)   1/4 (25.00%)   13/20 (65.00%) 
Blood and lymphatic system disorders       
Thrombocytopenia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Cardiac disorders       
Atrial fibrillation * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Abdominal pain upper * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Duodenal obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Pancreatitis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
General disorders       
Disease progression * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Oedema peripheral * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hepatobiliary disorders       
Bile duct obstruction * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hepatic failure * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Infections and infestations       
Pneumonia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications       
Infusion related reaction * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Investigations       
Blood bilirubin increased * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders       
Hyperglycaemia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hypoalbuminaemia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Nervous system disorders       
Cerebrovascular accident * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Psychiatric disorders       
Mental status changes * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders       
Pneumonitis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Pulmonary embolism * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Vascular disorders       
Hypotension * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
1
Term from vocabulary, MedDRA (14.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
PEGPH20 1.0 μg/kg PEGPH20 1.6 μg/kg PEGPH20 3.0 μg/kg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/4 (100.00%)   4/4 (100.00%)   19/20 (95.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  1/4 (25.00%)  1/4 (25.00%)  8/20 (40.00%) 
Leukopenia * 1  0/4 (0.00%)  1/4 (25.00%)  2/20 (10.00%) 
Lymphopenia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Neutropenia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Splenic infarction * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Thrombocytopenia * 1  3/4 (75.00%)  1/4 (25.00%)  9/20 (45.00%) 
Thrombocytosis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Cardiac disorders       
Bradycardia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Pericarditis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Sinus tachycardia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Tachycardia * 1  1/4 (25.00%)  1/4 (25.00%)  2/20 (10.00%) 
Arrhythmia * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Ear and labyrinth disorders       
Ear discomfort * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Tinnitus * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Vertigo * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Eye disorders       
Diplopia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Eyelid pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Vision blurred * 1  1/4 (25.00%)  0/4 (0.00%)  3/20 (15.00%) 
Gastrointestinal disorders       
Abdominal distension * 1  2/4 (50.00%)  0/4 (0.00%)  1/20 (5.00%) 
Abdominal pain * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Abdominal pain lower * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Abdominal pain upper * 1  2/4 (50.00%)  1/4 (25.00%)  3/20 (15.00%) 
Abdominal tenderness * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Ascites * 1  0/4 (0.00%)  2/4 (50.00%)  0/20 (0.00%) 
Constipation * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Diarrhoea * 1  0/4 (0.00%)  1/4 (25.00%)  6/20 (30.00%) 
Dry mouth * 1  1/4 (25.00%)  0/4 (0.00%)  2/20 (10.00%) 
Dyspepsia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Dysphagia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Epigastric discomfort * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Eructation * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Flatulence * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Gastritis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Gastrointestinal sounds abnormal * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Lip oedema * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Lip pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Mouth ulceration * 1  0/4 (0.00%)  1/4 (25.00%)  1/20 (5.00%) 
Nausea * 1  2/4 (50.00%)  0/4 (0.00%)  8/20 (40.00%) 
Oral pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Rectal haemorrhage * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Retching * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Sensitivity of teeth * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Stomatitis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Tongue discolouration * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Vomiting * 1  2/4 (50.00%)  0/4 (0.00%)  5/20 (25.00%) 
General disorders       
Application site rash * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Asthenia * 1  1/4 (25.00%)  0/4 (0.00%)  6/20 (30.00%) 
Catheter site erythema * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Chest discomfort * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Chills * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Early satiety * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Fatigue * 1  2/4 (50.00%)  1/4 (25.00%)  11/20 (55.00%) 
Injection site extravasation * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Malaise * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Mucosal inflammation * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Oedema peripheral * 1  3/4 (75.00%)  2/4 (50.00%)  11/20 (55.00%) 
Pyrexia * 1  2/4 (50.00%)  2/4 (50.00%)  1/20 (5.00%) 
Thirst * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Hepatobiliary disorders       
Bile duct stenosis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hyperbilirubinaemia * 1  0/4 (0.00%)  1/4 (25.00%)  2/20 (10.00%) 
Infections and infestations       
Candidiasis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Fungal infection * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Oral candidiasis * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Pneumonia * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Upper respiratory tract infection * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Injury, poisoning and procedural complications       
Contrast media reaction * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Excoriation * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Fall * 1  1/4 (25.00%)  0/4 (0.00%)  2/20 (10.00%) 
Infusion related reaction * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Procedural pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Spinal compression fracture * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Investigations       
Alanine aminotransferase increased * 1  0/4 (0.00%)  1/4 (25.00%)  2/20 (10.00%) 
Aspartate aminotransferase increased * 1  0/4 (0.00%)  1/4 (25.00%)  2/20 (10.00%) 
Blood alkaline phosphatase increased * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Blood bilirubin increased * 1  0/4 (0.00%)  1/4 (25.00%)  1/20 (5.00%) 
Eastern Cooperative Oncology Group performance status worsened * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Neutrophil count decreased * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Respiratory rate increased * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Weight decreased * 1  1/4 (25.00%)  0/4 (0.00%)  2/20 (10.00%) 
Weight increased * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Metabolism and nutrition disorders       
Decreased appetite * 1  0/4 (0.00%)  1/4 (25.00%)  8/20 (40.00%) 
Dehydration * 1  1/4 (25.00%)  0/4 (0.00%)  2/20 (10.00%) 
Fluid retention * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Glucose tolerance impaired * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Hyperglycaemia * 1  1/4 (25.00%)  1/4 (25.00%)  0/20 (0.00%) 
Hypoalbuminaemia * 1  1/4 (25.00%)  0/4 (0.00%)  4/20 (20.00%) 
Hypocalcaemia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hypoglycaemia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hypokalaemia * 1  1/4 (25.00%)  1/4 (25.00%)  3/20 (15.00%) 
Hypomagnesaemia * 1  0/4 (0.00%)  1/4 (25.00%)  2/20 (10.00%) 
Hyponatraemia * 1  0/4 (0.00%)  0/4 (0.00%)  3/20 (15.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  1/4 (25.00%)  1/4 (25.00%)  6/20 (30.00%) 
Back pain * 1  1/4 (25.00%)  1/4 (25.00%)  2/20 (10.00%) 
Bone pain * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Intervertebral disc degeneration * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Muscle atrophy * 1  2/4 (50.00%)  0/4 (0.00%)  0/20 (0.00%) 
Muscle spasms * 1  3/4 (75.00%)  0/4 (0.00%)  12/20 (60.00%) 
Muscular weakness * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Musculoskeletal discomfort * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Musculoskeletal pain * 1  1/4 (25.00%)  0/4 (0.00%)  2/20 (10.00%) 
Myalgia * 1  2/4 (50.00%)  0/4 (0.00%)  10/20 (50.00%) 
Pain in extremity * 1  2/4 (50.00%)  0/4 (0.00%)  4/20 (20.00%) 
Pain in jaw * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer pain * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Nervous system disorders       
Basal ganglia infarction * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Cognitive disorder * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Dizziness * 1  0/4 (0.00%)  1/4 (25.00%)  3/20 (15.00%) 
Dysgeusia * 1  3/4 (75.00%)  0/4 (0.00%)  2/20 (10.00%) 
Headache * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hypoaesthesia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Neuropathy peripheral * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Presyncope * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Syncope * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Tremor * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Psychiatric disorders       
Anger * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Anxiety * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Depression * 1  0/4 (0.00%)  0/4 (0.00%)  3/20 (15.00%) 
Insomnia * 1  1/4 (25.00%)  1/4 (25.00%)  5/20 (25.00%) 
Mental status changes * 1  1/4 (25.00%)  1/4 (25.00%)  0/20 (0.00%) 
Renal and urinary disorders       
Renal failure acute * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Urinary hesitation * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Urinary incontinence * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Reproductive system and breast disorders       
Erectile dysfunction * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Penile oedema * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Scrotal oedema * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Respiratory, thoracic and mediastinal disorders       
Atelectasis * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Cough * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Dysphonia * 1  0/4 (0.00%)  0/4 (0.00%)  3/20 (15.00%) 
Dyspnoea * 1  1/4 (25.00%)  0/4 (0.00%)  3/20 (15.00%) 
Dyspnoea exertional * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Epistaxis * 1  0/4 (0.00%)  1/4 (25.00%)  1/20 (5.00%) 
Hiccups * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Oropharyngeal pain * 1  0/4 (0.00%)  1/4 (25.00%)  0/20 (0.00%) 
Pleural effusion * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Productive cough * 1  0/4 (0.00%)  0/4 (0.00%)  3/20 (15.00%) 
Pulmonary embolism * 1  0/4 (0.00%)  0/4 (0.00%)  3/20 (15.00%) 
Sinus congestion * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Skin and subcutaneous tissue disorders       
Alopecia * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Decubitus ulcer * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Erythema * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Hyperhidrosis * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Night sweats * 1  1/4 (25.00%)  0/4 (0.00%)  2/20 (10.00%) 
Petechiae * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Pruritus * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Rash maculo-papular * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Rash pruritic * 1  1/4 (25.00%)  0/4 (0.00%)  1/20 (5.00%) 
Skin ulcer * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Vascular disorders       
Deep vein thrombosis * 1  2/4 (50.00%)  0/4 (0.00%)  0/20 (0.00%) 
Flushing * 1  0/4 (0.00%)  0/4 (0.00%)  2/20 (10.00%) 
Hypertension * 1  0/4 (0.00%)  1/4 (25.00%)  1/20 (5.00%) 
Hypotension * 1  0/4 (0.00%)  0/4 (0.00%)  3/20 (15.00%) 
Jugular vein thrombosis * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
Lymphoedema * 1  0/4 (0.00%)  0/4 (0.00%)  1/20 (5.00%) 
Venous thrombosis * 1  1/4 (25.00%)  0/4 (0.00%)  0/20 (0.00%) 
1
Term from vocabulary, MedDRA (14.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
All information obtained as a result of this study or during the conduct of this study will be regarded as confidential. The Investigator agrees to use the information for the purpose of carrying out this study and for no other purpose, unless written permission from the sponsor (Halozyme) is obtained.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dimitrios Chondros, M.D., Chief Medical Officer
Organization: Halozyme Therapeutics
Phone: 858-794-8889
EMail: dchondros@halozyme.com
Layout table for additonal information
Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01453153    
Other Study ID Numbers: Halo-109-201
First Submitted: October 13, 2011
First Posted: October 17, 2011
Results First Submitted: September 25, 2018
Results First Posted: November 30, 2018
Last Update Posted: November 30, 2018