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A Study of PEGylated Recombinant Human Hyaluronidase in Combination With Nab-Paclitaxel Plus Gemcitabine Compared With Placebo Plus Nab-Paclitaxel and Gemcitabine in Participants With Hyaluronan-High Stage IV Previously Untreated Pancreatic Ductal Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT02715804
Recruitment Status : Terminated (Sponsor decision)
First Posted : March 22, 2016
Results First Posted : July 14, 2020
Last Update Posted : July 14, 2020
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 Pancreatic Ductal Carcinoma
Interventions Other: Biological: PEGylated Recombinant Human Hyaluronidase (PEGPH20)
Drug: Placebo
Drug: nab-Paclitaxel
Drug: Gemcitabine
Enrollment 492
Recruitment Details A total of 492 participants were enrolled from 14 March 2016 through 26 December 2018 in 20 countries.
Pre-assignment Details A total of 492 participants were enrolled and randomized in 2:1 ratio to received either PAG (PEGPH20 + Nab-paclitaxel + Gemcitabine) or AG (Placebo + Nab-paclitaxel + Gemcitabine).
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description Participants received 3.0 micrograms/kilogram (μg/kg) PEGPH20 as an intravenous (IV) infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 milligrams/square meter (mg/m^2) nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks). Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Period Title: Overall Study
Started 327 165
Received at Least 1 Dose of Study Drug 323 158
Safety Population [1] 325 [2] 156 [3]
Completed 98 52
Not Completed 229 113
Reason Not Completed
Death             222             106
Withdrawal by Subject             5             4
Other than specified             2             3
[1]
Received at least 1 dose of study medication, and analyzed according to the treatment they received.
[2]
3 participants randomized to AG but received PAG
[3]
1 participant randomized to PAG but received AG
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine Total
Hide Arm/Group Description Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks). Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks). Total of all reporting groups
Overall Number of Baseline Participants 327 165 492
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 327 participants 165 participants 492 participants
63.8  (9.62) 62.3  (9.50) 63.3  (9.60)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 327 participants 165 participants 492 participants
Female
147
  45.0%
85
  51.5%
232
  47.2%
Male
180
  55.0%
80
  48.5%
260
  52.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 327 participants 165 participants 492 participants
Hispanic or Latino
24
   7.3%
11
   6.7%
35
   7.1%
Not Hispanic or Latino
267
  81.7%
138
  83.6%
405
  82.3%
Unknown or Not Reported
36
  11.0%
16
   9.7%
52
  10.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 327 participants 165 participants 492 participants
White/Caucasian
266
  81.3%
126
  76.4%
392
  79.7%
Black or African American
11
   3.4%
5
   3.0%
16
   3.3%
Asian
33
  10.1%
24
  14.5%
57
  11.6%
Other
17
   5.2%
10
   6.1%
27
   5.5%
1.Primary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time from randomization until death from any cause. Overall survival was analyzed using Kaplan-Meier methods.
Time Frame From randomization until death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 327 165
Median (95% Confidence Interval)
Unit of Measure: months
11.2
(10.3 to 12.3)
11.5
(9.0 to 12.5)
2.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as the time from randomization until the first occurrence of radiological disease progression, as determined by the blinded Central Imaging Vendor (CIV) based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, or death from any cause during the treatment period. Disease progression was defined as at least a 20 percent (%) increase in sum of diameters of target lesions, taking as reference the smallest sum on study thus far, nadir (this included baseline sum if that was the smallest on study); Sum must also demonstrate an absolute increase of at least 5 millimeters (mm); Appearance of one or more new lesions; Unequivocal progression of existing non-target lesions. Surviving participants without disease progression were censored for PFS analysis at the date of last evaluable post-baseline tumor assessment. Surviving participants without any post-baseline disease assessment were censored on Day 1. PFS was estimated using Kaplan-Meier method.
Time Frame From the date of randomization until disease progression or death from any cause (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 327 165
Median (95% Confidence Interval)
Unit of Measure: months
7.1
(5.5 to 7.4)
7.1
(4.8 to 8.3)
3.Secondary Outcome
Title Objective Response Rate (ORR): Percentage of Participants With Objective Response
Hide Description ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR) as determined by the blinded CIV based on RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame From the date of randomization until CR or PR (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 327 165
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
47.1
(41.6 to 52.7)
36.4
(29.0 to 44.2)
4.Secondary Outcome
Title Duration of Response (DOR)
Hide Description DOR was defined as the time from the first objective response of CR or PR until disease progression (as determined by the blinded CIV based on RECIST version 1.1) or death within 14 days of last dose of study treatment or randomization. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study thus far, the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of one or more new lesions; and unequivocal progression of existing non-target lesions. DOR was analyzed using Kaplan-Meier methods.
Time Frame From date of first objective response (CR or PR) until date of first disease progression (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants. Here, 'Overall number of participants analyzed' signifies participants with objective response.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 154 60
Median (95% Confidence Interval)
Unit of Measure: months
6.1
(5.5 to 7.8)
7.4
(5.3 to 9.4)
5.Secondary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs)
Hide Description An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were defined as AEs that begin or worsen in severity during or after the participant's first dose of study treatment and no later than 30 days after the date of the last dose of study treatment and/or any treatment-related AE regardless of the onset date. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Time Frame From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 325 156
Measure Type: Count of Participants
Unit of Measure: Participants
325
 100.0%
156
 100.0%
6.Secondary Outcome
Title Number of Participants With Worst Post-Baseline Hematology and Chemistry (Clinical Laboratory Parameters) Severity Grade During the Study
Hide Description Severity grade associated with a laboratory parameter value was determined using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening. Grade 0 indicates evaluable lab records but not fall into any CTCAE grade for certain CTCAE term. A worst post-baseline grade shift was defined as the worst change that occurred at any measured timepoint during study. Hematology abnormalities: anemia(hemoglobin decreased), lymphocyte count decreased, lymphocyte count increased, neutropenia(neutrophil count decreased), thrombocytopenia(platelet count decreased), and leukopenia(white blood cell decreased). Chemistry abnormalities: hypoalbuminemia, alkaline phosphatase increased, alanine aminotransferase increased, aspartate aminotransferase increased, hyperbilirubinemia, hypo- and hypercalcemia, creatinine increased, hypo- and hyperglycaemia, hypo- and hyperkalemia, hypo- and hypermagnesemia, hypo- and hypernatremia.
Time Frame From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received. Here, 'Number analyzed' signifies participants evaluable for specified categories.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 325 156
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia: Post-baseline Number Analyzed 321 participants 155 participants
Grade 0
6
   1.9%
3
   1.9%
Grade 1
84
  26.2%
41
  26.5%
Grade 2
164
  51.1%
74
  47.7%
Grade 3
67
  20.9%
37
  23.9%
Grade 4
0
   0.0%
0
   0.0%
Lymphocyte count decreased: Post-baseline Number Analyzed 321 participants 155 participants
Grade 0
33
  10.3%
17
  11.0%
Grade 1
83
  25.9%
46
  29.7%
Grade 2
102
  31.8%
46
  29.7%
Grade 3
90
  28.0%
40
  25.8%
Grade 4
13
   4.0%
6
   3.9%
Lymphocyte count increased: Post-baseline Number Analyzed 321 participants 155 participants
Grade 0
302
  94.1%
150
  96.8%
Grade 1
0
   0.0%
0
   0.0%
Grade 2
19
   5.9%
5
   3.2%
Grade 3
0
   0.0%
0
   0.0%
Grade 4
0
   0.0%
0
   0.0%
Neutropenia: Post-baseline Number Analyzed 321 participants 155 participants
Grade 0
85
  26.5%
31
  20.0%
Grade 1
27
   8.4%
11
   7.1%
Grade 2
57
  17.8%
30
  19.4%
Grade 3
98
  30.5%
48
  31.0%
Grade 4
54
  16.8%
35
  22.6%
Thrombocytopenia: Post-baseline Number Analyzed 322 participants 155 participants
Grade 0
52
  16.1%
32
  20.6%
Grade 1
134
  41.6%
63
  40.6%
Grade 2
76
  23.6%
36
  23.2%
Grade 3
51
  15.8%
20
  12.9%
Grade 4
9
   2.8%
4
   2.6%
Leukopenia: Post-baseline Number Analyzed 321 participants 155 participants
Grade 0
74
  23.1%
32
  20.6%
Grade 1
30
   9.3%
15
   9.7%
Grade 2
100
  31.2%
43
  27.7%
Grade 3
87
  27.1%
51
  32.9%
Grade 4
30
   9.3%
14
   9.0%
Hypoalbuminemia (Albumin): Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
19
   6.0%
46
  29.7%
Grade 1
102
  32.1%
62
  40.0%
Grade 2
185
  58.2%
44
  28.4%
Grade 3
12
   3.8%
3
   1.9%
Grade 4
0
   0.0%
0
   0.0%
Alkaline phosphatase increased: Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
135
  42.5%
57
  36.8%
Grade 1
114
  35.8%
62
  40.0%
Grade 2
50
  15.7%
26
  16.8%
Grade 3
19
   6.0%
10
   6.5%
Grade 4
0
   0.0%
0
   0.0%
Alanine aminotransferase increased: Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
69
  21.7%
33
  21.3%
Grade 1
155
  48.7%
72
  46.5%
Grade 2
43
  13.5%
32
  20.6%
Grade 3
51
  16.0%
17
  11.0%
Grade 4
0
   0.0%
1
   0.6%
Aspartate aminotransferase increased:Post-baseline Number Analyzed 319 participants 155 participants
Grade 0
77
  24.1%
28
  18.1%
Grade 1
168
  52.7%
96
  61.9%
Grade 2
49
  15.4%
17
  11.0%
Grade 3
25
   7.8%
13
   8.4%
Grade 4
0
   0.0%
1
   0.6%
Hyperbilirubinemia: Post-baseline Number Analyzed 319 participants 155 participants
Grade 0
237
  74.3%
125
  80.6%
Grade 1
36
  11.3%
9
   5.8%
Grade 2
31
   9.7%
15
   9.7%
Grade 3
12
   3.8%
6
   3.9%
Grade 4
3
   0.9%
0
   0.0%
Hypocalcemia (calcium): Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
224
  70.4%
119
  76.8%
Grade 1
68
  21.4%
30
  19.4%
Grade 2
22
   6.9%
6
   3.9%
Grade 3
4
   1.3%
0
   0.0%
Grade 4
0
   0.0%
0
   0.0%
Hypercalcemia (calcium): Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
278
  87.4%
148
  95.5%
Grade 1
34
  10.7%
6
   3.9%
Grade 2
3
   0.9%
0
   0.0%
Grade 3
3
   0.9%
1
   0.6%
Grade 4
0
   0.0%
0
   0.0%
Creatinine increased: Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
267
  84.0%
135
  87.1%
Grade 1
45
  14.2%
16
  10.3%
Grade 2
6
   1.9%
4
   2.6%
Grade 3
0
   0.0%
0
   0.0%
Grade 4
0
   0.0%
0
   0.0%
Hypoglycemia (glucose): Post-baseline Number Analyzed 320 participants 155 participants
Grade 0
292
  91.3%
140
  90.3%
Grade 1
17
   5.3%
9
   5.8%
Grade 2
7
   2.2%
1
   0.6%
Grade 3
3
   0.9%
1
   0.6%
Grade 4
1
   0.3%
4
   2.6%
Hyperglycemia (glucose): Post-baseline Number Analyzed 320 participants 155 participants
Grade 0
31
   9.7%
24
  15.5%
Grade 1
90
  28.1%
45
  29.0%
Grade 2
119
  37.2%
44
  28.4%
Grade 3
76
  23.8%
40
  25.8%
Grade 4
4
   1.3%
2
   1.3%
Hypokalemia (potassium): Post-baseline Number Analyzed 319 participants 155 participants
Grade 0
202
  63.3%
104
  67.1%
Grade 1
89
  27.9%
38
  24.5%
Grade 2
0
   0.0%
0
   0.0%
Grade 3
24
   7.5%
11
   7.1%
Grade 4
4
   1.3%
2
   1.3%
Hyperkalemia (potassium): Post-baseline Number Analyzed 319 participants 155 participants
Grade 0
245
  76.8%
122
  78.7%
Grade 1
44
  13.8%
19
  12.3%
Grade 2
21
   6.6%
11
   7.1%
Grade 3
7
   2.2%
3
   1.9%
Grade 4
2
   0.6%
0
   0.0%
Hypomagnesemia (magnesium): Post-baseline Number Analyzed 318 participants 154 participants
Grade 0
209
  65.7%
113
  73.4%
Grade 1
95
  29.9%
36
  23.4%
Grade 2
9
   2.8%
5
   3.2%
Grade 3
4
   1.3%
0
   0.0%
Grade 4
1
   0.3%
0
   0.0%
Hypermagnesemia (magnesium): Post-baseline Number Analyzed 318 participants 154 participants
Grade 0
306
  96.2%
150
  97.4%
Grade 1
8
   2.5%
4
   2.6%
Grade 2
0
   0.0%
0
   0.0%
Grade 3
4
   1.3%
0
   0.0%
Grade 4
0
   0.0%
0
   0.0%
Hyponatremia (sodium): Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
96
  30.2%
49
  31.6%
Grade 1
167
  52.5%
85
  54.8%
Grade 2
0
   0.0%
0
   0.0%
Grade 3
54
  17.0%
21
  13.5%
Grade 4
1
   0.3%
0
   0.0%
Hypernatremia (sodium): Post-baseline Number Analyzed 318 participants 155 participants
Grade 0
308
  96.9%
153
  98.7%
Grade 1
9
   2.8%
2
   1.3%
Grade 2
0
   0.0%
0
   0.0%
Grade 3
0
   0.0%
0
   0.0%
Grade 4
1
   0.3%
0
   0.0%
7.Secondary Outcome
Title Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)
Hide Description ECGs including clinical significance was evaluated by the Investigator. Criteria for clinical significance were as per investigator's discretion.
Time Frame From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 325 156
Measure Type: Count of Participants
Unit of Measure: Participants
8
   2.5%
4
   2.6%
8.Secondary Outcome
Title Number of Participants With Clinically Significant Abnormalities in Vital Signs
Hide Description Vital signs included measurement of blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), heart rate, and body weight. Criteria for clinical significance abnormalities were: Heart rate: <50 beats per minute (bpm), >120 bpm, >=30 bpm increase from baseline, >=30 bpm decrease from baseline. SBP: >140 millimeters of mercury (mmHg) and increase from baseline >20 mmHg, >180 mmHg, <90 mmHg and decrease from baseline >10 mmHg. DBP: >90 mmHg and increase from baseline >20 mmHg, >105 mmHg, <60 mmHg and decrease from baseline >10 mmHg. Change in weight: >=5% increase from baseline, >=5% decrease from baseline.
Time Frame From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received.
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description:
Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks).
Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
Overall Number of Participants Analyzed 325 156
Measure Type: Count of Participants
Unit of Measure: Participants
Heart rate: <50 bpm
7
   2.2%
4
   2.6%
Heart rate: >120 bpm
47
  14.5%
13
   8.3%
Heart rate: >=30 bpm increase from baseline
102
  31.4%
26
  16.7%
Heart rate: >=30 bpm decrease from baseline
38
  11.7%
19
  12.2%
SBP: >140 mmHg and increase from baseline >20 mmHg
75
  23.1%
37
  23.7%
SBP: >180 mmHg
6
   1.8%
4
   2.6%
SBP: <90 mmHg and decrease from baseline >10 mmHg
60
  18.5%
17
  10.9%
DBP: >90 mmHg and increase from baseline >20 mmHg
21
   6.5%
10
   6.4%
DBP: >105 mmHg
8
   2.5%
6
   3.8%
DBP: <60 mmHg and decrease from baseline >10 mmHg
142
  43.7%
56
  35.9%
Change in weight: >=5% increase from baseline
85
  26.2%
52
  33.3%
Change in weight: >=5% decrease from baseline
151
  46.5%
57
  36.5%
Time Frame From administration of first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 150.1 weeks for PAG, and 83.9 weeks for AG)
Adverse Event Reporting Description Safety population included all participants who received at least 1 dose of study medication, and analyzed according to the treatment they actually received. 3 participants randomized to AG but received PAG, hence included in PAG arm for safety assessment and 1 participant randomized to PAG but received AG, hence included in AG arm for safety assessment.
 
Arm/Group Title PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Hide Arm/Group Description Participants received 3.0 μg/kg PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisted of 4 weeks [Week 4 of every cycle was a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continued until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 150.1 weeks). Participants received placebo matching to PEGPH20 as an IV infusion, twice weekly for Weeks 1 to 3 of Cycle 1 (each cycle consisting of 4 weeks [Week 4 of every cycle will be a rest week with no treatment]), then once weekly for Weeks 1 to 3 of Cycle 2 and beyond in combination with 125 mg/m^2 nab-paclitaxel as an IV infusion and 1000 mg/m^2 gemcitabine as an IV infusion, once weekly for Weeks 1 to 3 of all treatment cycles. Treatment was continue until disease progression, unacceptable toxicity, death, or withdrawal of consent (Maximum exposure: 83.9 weeks).
All-Cause Mortality
PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   222/325 (68.31%)   106/156 (67.95%) 
Hide Serious Adverse Events
PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   187/325 (57.54%)   80/156 (51.28%) 
Blood and lymphatic system disorders     
Febrile neutropenia  1  16/325 (4.92%)  10/156 (6.41%) 
Anaemia  1  9/325 (2.77%)  3/156 (1.92%) 
Neutropenia  1  8/325 (2.46%)  4/156 (2.56%) 
Thrombocytopenia  1  6/325 (1.85%)  1/156 (0.64%) 
Pancytopenia  1  4/325 (1.23%)  2/156 (1.28%) 
Leukopenia  1  2/325 (0.62%)  1/156 (0.64%) 
Disseminated intravascular coagulation  1  1/325 (0.31%)  0/156 (0.00%) 
Leukocytosis  1  1/325 (0.31%)  0/156 (0.00%) 
Lymphopenia  1  0/325 (0.00%)  1/156 (0.64%) 
Splenic infarction  1  1/325 (0.31%)  0/156 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  8/325 (2.46%)  0/156 (0.00%) 
Supraventricular tachycardia  1  2/325 (0.62%)  1/156 (0.64%) 
Pericardial effusion  1  1/325 (0.31%)  1/156 (0.64%) 
Acute coronary syndrome  1  0/325 (0.00%)  1/156 (0.64%) 
Acute left ventricular failure  1  1/325 (0.31%)  0/156 (0.00%) 
Angina pectoris  1  1/325 (0.31%)  0/156 (0.00%) 
Atrial flutter  1  1/325 (0.31%)  0/156 (0.00%) 
Cardiac arrest  1  1/325 (0.31%)  0/156 (0.00%) 
Cardiac failure  1  0/325 (0.00%)  1/156 (0.64%) 
Cardiac failure congestive  1  1/325 (0.31%)  0/156 (0.00%) 
Myocardial infarction  1  0/325 (0.00%)  1/156 (0.64%) 
Tachycardia  1  1/325 (0.31%)  0/156 (0.00%) 
Ventricular tachycardia  1  1/325 (0.31%)  0/156 (0.00%) 
Congenital, familial and genetic disorders     
Pyloric stenosis  1  1/325 (0.31%)  0/156 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  1/325 (0.31%)  0/156 (0.00%) 
Eye disorders     
Retinal detachment  1  1/325 (0.31%)  0/156 (0.00%) 
Gastrointestinal disorders     
Diarrhoea  1  13/325 (4.00%)  7/156 (4.49%) 
Abdominal pain  1  10/325 (3.08%)  6/156 (3.85%) 
Vomiting  1  9/325 (2.77%)  5/156 (3.21%) 
Colitis  1  4/325 (1.23%)  3/156 (1.92%) 
Nausea  1  4/325 (1.23%)  3/156 (1.92%) 
Small intestinal obstruction  1  3/325 (0.92%)  2/156 (1.28%) 
Upper gastrointestinal haemorrhage  1  5/325 (1.54%)  0/156 (0.00%) 
Ascites  1  4/325 (1.23%)  0/156 (0.00%) 
Ileus  1  3/325 (0.92%)  1/156 (0.64%) 
Diverticular perforation  1  2/325 (0.62%)  1/156 (0.64%) 
Gastrointestinal haemorrhage  1  3/325 (0.92%)  0/156 (0.00%) 
Abdominal pain upper  1  1/325 (0.31%)  1/156 (0.64%) 
Duodenal obstruction  1  2/325 (0.62%)  0/156 (0.00%) 
Intestinal obstruction  1  2/325 (0.62%)  0/156 (0.00%) 
Pancreatitis acute  1  2/325 (0.62%)  0/156 (0.00%) 
Small intestinal haemorrhage  1  1/325 (0.31%)  1/156 (0.64%) 
Abdominal wall haematoma  1  0/325 (0.00%)  1/156 (0.64%) 
Constipation  1  1/325 (0.31%)  0/156 (0.00%) 
Duodenal stenosis  1  1/325 (0.31%)  0/156 (0.00%) 
Duodenal ulcer haemorrhage  1  1/325 (0.31%)  0/156 (0.00%) 
Duodenal ulcer perforation  1  0/325 (0.00%)  1/156 (0.64%) 
Dysphagia  1  1/325 (0.31%)  0/156 (0.00%) 
Enterovesical fistula  1  1/325 (0.31%)  0/156 (0.00%) 
Fistula of small intestine  1  1/325 (0.31%)  0/156 (0.00%) 
Gastric ulcer  1  1/325 (0.31%)  0/156 (0.00%) 
Gastritis  1  1/325 (0.31%)  0/156 (0.00%) 
Gastrointestinal fistula  1  0/325 (0.00%)  1/156 (0.64%) 
Gastrointestinal motility disorder  1  1/325 (0.31%)  0/156 (0.00%) 
Impaired gastric emptying  1  0/325 (0.00%)  1/156 (0.64%) 
Inguinal hernia  1  0/325 (0.00%)  1/156 (0.64%) 
Intestinal perforation  1  1/325 (0.31%)  0/156 (0.00%) 
Intra-abdominal fluid collection  1  1/325 (0.31%)  0/156 (0.00%) 
Jejunal ulcer  1  0/325 (0.00%)  1/156 (0.64%) 
Large intestine perforation  1  1/325 (0.31%)  0/156 (0.00%) 
Mallory-Weiss syndrome  1  0/325 (0.00%)  1/156 (0.64%) 
Obstruction gastric  1  1/325 (0.31%)  0/156 (0.00%) 
Oesophagitis  1  0/325 (0.00%)  1/156 (0.64%) 
Pancreatic pseudocyst  1  1/325 (0.31%)  0/156 (0.00%) 
Pancreatitis  1  0/325 (0.00%)  1/156 (0.64%) 
Peptic ulcer perforation  1  1/325 (0.31%)  0/156 (0.00%) 
Rectal haemorrhage  1  1/325 (0.31%)  0/156 (0.00%) 
Stomatitis  1  1/325 (0.31%)  0/156 (0.00%) 
Subileus  1  1/325 (0.31%)  0/156 (0.00%) 
General disorders     
Pyrexia  1  23/325 (7.08%)  8/156 (5.13%) 
Asthenia  1  6/325 (1.85%)  2/156 (1.28%) 
Fatigue  1  6/325 (1.85%)  1/156 (0.64%) 
General physical health deterioration  1  4/325 (1.23%)  0/156 (0.00%) 
Oedema peripheral  1  3/325 (0.92%)  0/156 (0.00%) 
Chills  1  0/325 (0.00%)  1/156 (0.64%) 
Generalised oedema  1  1/325 (0.31%)  0/156 (0.00%) 
Influenza like illness  1  0/325 (0.00%)  1/156 (0.64%) 
Infusion site extravasation  1  1/325 (0.31%)  0/156 (0.00%) 
Malaise  1  1/325 (0.31%)  0/156 (0.00%) 
Mucosal inflammation  1  0/325 (0.00%)  1/156 (0.64%) 
Multiple organ dysfunction syndrome  1  1/325 (0.31%)  0/156 (0.00%) 
Pain  1  0/325 (0.00%)  1/156 (0.64%) 
Peripheral swelling  1  1/325 (0.31%)  0/156 (0.00%) 
Hepatobiliary disorders     
Cholangitis  1  8/325 (2.46%)  6/156 (3.85%) 
Bile duct obstruction  1  6/325 (1.85%)  0/156 (0.00%) 
Cholecystitis  1  4/325 (1.23%)  2/156 (1.28%) 
Bile duct stenosis  1  2/325 (0.62%)  1/156 (0.64%) 
Portal vein thrombosis  1  0/325 (0.00%)  2/156 (1.28%) 
Cholangitis acute  1  0/325 (0.00%)  1/156 (0.64%) 
Hepatic vein thrombosis  1  1/325 (0.31%)  0/156 (0.00%) 
Hyperbilirubinaemia  1  1/325 (0.31%)  0/156 (0.00%) 
Hypertransaminasaemia  1  1/325 (0.31%)  0/156 (0.00%) 
Jaundice cholestatic  1  1/325 (0.31%)  0/156 (0.00%) 
Immune system disorders     
Hypersensitivity  1  1/325 (0.31%)  0/156 (0.00%) 
Infections and infestations     
Sepsis  1  22/325 (6.77%)  4/156 (2.56%) 
Pneumonia  1  10/325 (3.08%)  6/156 (3.85%) 
Liver abscess  1  8/325 (2.46%)  2/156 (1.28%) 
Septic shock  1  6/325 (1.85%)  1/156 (0.64%) 
Bacteraemia  1  4/325 (1.23%)  1/156 (0.64%) 
Urosepsis  1  4/325 (1.23%)  1/156 (0.64%) 
Device related infection  1  2/325 (0.62%)  1/156 (0.64%) 
Infection  1  2/325 (0.62%)  1/156 (0.64%) 
Pneumocystis jirovecii pneumonia  1  1/325 (0.31%)  2/156 (1.28%) 
Abdominal abscess  1  2/325 (0.62%)  0/156 (0.00%) 
Clostridium difficile colitis  1  2/325 (0.62%)  0/156 (0.00%) 
Lower respiratory tract infection  1  0/325 (0.00%)  2/156 (1.28%) 
Lung infection  1  2/325 (0.62%)  0/156 (0.00%) 
Peritonitis  1  1/325 (0.31%)  1/156 (0.64%) 
Peritonitis bacterial  1  1/325 (0.31%)  1/156 (0.64%) 
Skin infection  1  2/325 (0.62%)  0/156 (0.00%) 
Upper respiratory tract infection  1  2/325 (0.62%)  0/156 (0.00%) 
Urinary tract infection  1  2/325 (0.62%)  0/156 (0.00%) 
Abdominal infection  1  1/325 (0.31%)  0/156 (0.00%) 
Abdominal wall infection  1  1/325 (0.31%)  0/156 (0.00%) 
Appendicitis perforated  1  1/325 (0.31%)  0/156 (0.00%) 
Arthritis bacterial  1  1/325 (0.31%)  0/156 (0.00%) 
Cellulitis  1  1/325 (0.31%)  0/156 (0.00%) 
Cholangitis infective  1  1/325 (0.31%)  0/156 (0.00%) 
Clostridium difficile infection  1  1/325 (0.31%)  0/156 (0.00%) 
Colonic abscess  1  0/325 (0.00%)  1/156 (0.64%) 
Diverticulitis  1  1/325 (0.31%)  0/156 (0.00%) 
Empyema  1  1/325 (0.31%)  0/156 (0.00%) 
Endocarditis staphylococcal  1  1/325 (0.31%)  0/156 (0.00%) 
Enterococcal bacteraemia  1  0/325 (0.00%)  1/156 (0.64%) 
Escherichia bacteraemia  1  0/325 (0.00%)  1/156 (0.64%) 
Escherichia sepsis  1  1/325 (0.31%)  0/156 (0.00%) 
Groin abscess  1  1/325 (0.31%)  0/156 (0.00%) 
Haematoma infection  1  1/325 (0.31%)  0/156 (0.00%) 
Hepatic infection  1  1/325 (0.31%)  0/156 (0.00%) 
Infective exacerbation of chronic obstructive airways disease  1  1/325 (0.31%)  0/156 (0.00%) 
Influenza  1  1/325 (0.31%)  0/156 (0.00%) 
Klebsiella bacteraemia  1  1/325 (0.31%)  0/156 (0.00%) 
Klebsiella infection  1  1/325 (0.31%)  0/156 (0.00%) 
Klebsiella sepsis  1  1/325 (0.31%)  0/156 (0.00%) 
Proteus infection  1  1/325 (0.31%)  0/156 (0.00%) 
Pseudomonas bronchitis  1  1/325 (0.31%)  0/156 (0.00%) 
Stenotrophomonas infection  1  1/325 (0.31%)  0/156 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/325 (0.31%)  1/156 (0.64%) 
Humerus fracture  1  0/325 (0.00%)  1/156 (0.64%) 
Vascular pseudoaneurysm  1  1/325 (0.31%)  0/156 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  3/325 (0.92%)  1/156 (0.64%) 
Neutrophil count decreased  1  3/325 (0.92%)  1/156 (0.64%) 
Platelet count decreased  1  2/325 (0.62%)  2/156 (1.28%) 
Aspartate aminotransferase increased  1  2/325 (0.62%)  1/156 (0.64%) 
Blood bilirubin increased  1  2/325 (0.62%)  0/156 (0.00%) 
Transaminases increased  1  1/325 (0.31%)  1/156 (0.64%) 
Blood creatine phosphokinase increased  1  0/325 (0.00%)  1/156 (0.64%) 
Blood creatinine increased  1  1/325 (0.31%)  0/156 (0.00%) 
Lipase increased  1  1/325 (0.31%)  0/156 (0.00%) 
Vitamin K decreased  1  1/325 (0.31%)  0/156 (0.00%) 
Weight decreased  1  1/325 (0.31%)  0/156 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  5/325 (1.54%)  3/156 (1.92%) 
Hypoglycaemia  1  5/325 (1.54%)  2/156 (1.28%) 
Decreased appetite  1  4/325 (1.23%)  1/156 (0.64%) 
Hyperglycaemia  1  3/325 (0.92%)  1/156 (0.64%) 
Hyponatraemia  1  3/325 (0.92%)  1/156 (0.64%) 
Hypokalaemia  1  3/325 (0.92%)  0/156 (0.00%) 
Cachexia  1  0/325 (0.00%)  1/156 (0.64%) 
Diabetes mellitus  1  1/325 (0.31%)  0/156 (0.00%) 
Hypercalcaemia  1  1/325 (0.31%)  0/156 (0.00%) 
Hyperkalaemia  1  1/325 (0.31%)  0/156 (0.00%) 
Hypochloraemia  1  1/325 (0.31%)  0/156 (0.00%) 
Malnutrition  1  1/325 (0.31%)  0/156 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscular weakness  1  2/325 (0.62%)  1/156 (0.64%) 
Myalgia  1  2/325 (0.62%)  1/156 (0.64%) 
Back pain  1  1/325 (0.31%)  1/156 (0.64%) 
Muscle spasms  1  1/325 (0.31%)  0/156 (0.00%) 
Musculoskeletal pain  1  1/325 (0.31%)  0/156 (0.00%) 
Myositis  1  1/325 (0.31%)  0/156 (0.00%) 
Rhabdomyolysis  1  1/325 (0.31%)  0/156 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer pain  1  2/325 (0.62%)  0/156 (0.00%) 
Malignant pleural effusion  1  1/325 (0.31%)  0/156 (0.00%) 
Nervous system disorders     
Syncope  1  3/325 (0.92%)  2/156 (1.28%) 
Cerebrovascular accident  1  4/325 (1.23%)  0/156 (0.00%) 
Cerebral ischaemia  1  1/325 (0.31%)  1/156 (0.64%) 
Ischaemic cerebral infarction  1  2/325 (0.62%)  0/156 (0.00%) 
Brachial plexopathy  1  1/325 (0.31%)  0/156 (0.00%) 
Dizziness  1  1/325 (0.31%)  0/156 (0.00%) 
Presyncope  1  1/325 (0.31%)  0/156 (0.00%) 
Radiculopathy  1  1/325 (0.31%)  0/156 (0.00%) 
Toxic encephalopathy  1  0/325 (0.00%)  1/156 (0.64%) 
Product Issues     
Device occlusion  1  1/325 (0.31%)  0/156 (0.00%) 
Psychiatric disorders     
Confusional state  1  2/325 (0.62%)  0/156 (0.00%) 
Anxiety  1  0/325 (0.00%)  1/156 (0.64%) 
Completed suicide  1  1/325 (0.31%)  0/156 (0.00%) 
Delirium  1  0/325 (0.00%)  1/156 (0.64%) 
Renal and urinary disorders     
Acute kidney injury  1  4/325 (1.23%)  0/156 (0.00%) 
Renal failure  1  2/325 (0.62%)  0/156 (0.00%) 
Haematuria  1  1/325 (0.31%)  0/156 (0.00%) 
Urine flow decreased  1  0/325 (0.00%)  1/156 (0.64%) 
Reproductive system and breast disorders     
Ovarian cyst  1 [1]  0/147 (0.00%)  1/85 (1.18%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  5/325 (1.54%)  3/156 (1.92%) 
Dyspnoea  1  7/325 (2.15%)  0/156 (0.00%) 
Pleural effusion  1  6/325 (1.85%)  1/156 (0.64%) 
Pneumonitis  1  6/325 (1.85%)  1/156 (0.64%) 
Hypoxia  1  4/325 (1.23%)  1/156 (0.64%) 
Respiratory failure  1  4/325 (1.23%)  1/156 (0.64%) 
Pneumothorax  1  1/325 (0.31%)  2/156 (1.28%) 
Acute respiratory failure  1  2/325 (0.62%)  0/156 (0.00%) 
Interstitial lung disease  1  1/325 (0.31%)  1/156 (0.64%) 
Pulmonary oedema  1  2/325 (0.62%)  0/156 (0.00%) 
Acute respiratory distress syndrome  1  0/325 (0.00%)  1/156 (0.64%) 
Aspiration  1  1/325 (0.31%)  0/156 (0.00%) 
Cough  1  1/325 (0.31%)  0/156 (0.00%) 
Haemoptysis  1  1/325 (0.31%)  0/156 (0.00%) 
Hydrothorax  1  1/325 (0.31%)  0/156 (0.00%) 
Pulmonary cavitation  1  1/325 (0.31%)  0/156 (0.00%) 
Pulmonary hypertension  1  1/325 (0.31%)  0/156 (0.00%) 
Skin and subcutaneous tissue disorders     
Toxic skin eruption  1  1/325 (0.31%)  0/156 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  8/325 (2.46%)  3/156 (1.92%) 
Hypotension  1  4/325 (1.23%)  0/156 (0.00%) 
Orthostatic hypotension  1  2/325 (0.62%)  1/156 (0.64%) 
Thrombophlebitis superficial  1  3/325 (0.92%)  0/156 (0.00%) 
Hypertension  1  1/325 (0.31%)  0/156 (0.00%) 
Hypertensive crisis  1  1/325 (0.31%)  0/156 (0.00%) 
Vena cava thrombosis  1  1/325 (0.31%)  0/156 (0.00%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
[1]
This is a gender-specific AE. Only female participants were at risk.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PAG: PEGPH20 + Nab-Paclitaxel + Gemcitabine AG: Placebo + Nab-Paclitaxel + Gemcitabine
Affected / at Risk (%) Affected / at Risk (%)
Total   198/325 (60.92%)   73/156 (46.79%) 
Blood and lymphatic system disorders     
Anaemia  1  139/325 (42.77%)  70/156 (44.87%) 
Neutropenia  1  106/325 (32.62%)  51/156 (32.69%) 
Thrombocytopenia  1  90/325 (27.69%)  32/156 (20.51%) 
Leukopenia  1  28/325 (8.62%)  15/156 (9.62%) 
Gastrointestinal disorders     
Nausea  1  149/325 (45.85%)  68/156 (43.59%) 
Diarrhoea  1  148/325 (45.54%)  73/156 (46.79%) 
Vomiting  1  100/325 (30.77%)  38/156 (24.36%) 
Constipation  1  85/325 (26.15%)  58/156 (37.18%) 
Abdominal pain  1  80/325 (24.62%)  43/156 (27.56%) 
Stomatitis  1  34/325 (10.46%)  9/156 (5.77%) 
Abdominal pain upper  1  23/325 (7.08%)  11/156 (7.05%) 
Dry mouth  1  22/325 (6.77%)  9/156 (5.77%) 
Dyspepsia  1  22/325 (6.77%)  10/156 (6.41%) 
Abdominal distension  1  19/325 (5.85%)  5/156 (3.21%) 
General disorders     
Oedema peripheral  1  198/325 (60.92%)  52/156 (33.33%) 
Fatigue  1  162/325 (49.85%)  70/156 (44.87%) 
Pyrexia  1  94/325 (28.92%)  49/156 (31.41%) 
Asthenia  1  74/325 (22.77%)  36/156 (23.08%) 
Chills  1  25/325 (7.69%)  10/156 (6.41%) 
Mucosal inflammation  1  23/325 (7.08%)  7/156 (4.49%) 
Peripheral swelling  1  7/325 (2.15%)  9/156 (5.77%) 
Infections and infestations     
Urinary tract infection  1  28/325 (8.62%)  11/156 (7.05%) 
Upper respiratory tract infection  1  18/325 (5.54%)  11/156 (7.05%) 
Injury, poisoning and procedural complications     
Fall  1  19/325 (5.85%)  4/156 (2.56%) 
Investigations     
Platelet count decreased  1  73/325 (22.46%)  36/156 (23.08%) 
Weight decreased  1  57/325 (17.54%)  14/156 (8.97%) 
Neutrophil count decreased  1  55/325 (16.92%)  39/156 (25.00%) 
Alanine aminotransferase increased  1  51/325 (15.69%)  25/156 (16.03%) 
White blood cell count decreased  1  44/325 (13.54%)  23/156 (14.74%) 
Aspartate aminotransferase increased  1  34/325 (10.46%)  17/156 (10.90%) 
Blood alkaline phosphatase increased  1  16/325 (4.92%)  8/156 (5.13%) 
Blood bilirubin increased  1  13/325 (4.00%)  11/156 (7.05%) 
Metabolism and nutrition disorders     
Decreased appetite  1  106/325 (32.62%)  42/156 (26.92%) 
Hypokalaemia  1  51/325 (15.69%)  23/156 (14.74%) 
Hypoalbuminaemia  1  48/325 (14.77%)  11/156 (7.05%) 
Dehydration  1  37/325 (11.38%)  8/156 (5.13%) 
Hyponatraemia  1  37/325 (11.38%)  10/156 (6.41%) 
Hyperglycaemia  1  30/325 (9.23%)  16/156 (10.26%) 
Hypocalcaemia  1  22/325 (6.77%)  4/156 (2.56%) 
Hypomagnesaemia  1  20/325 (6.15%)  10/156 (6.41%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  166/325 (51.08%)  15/156 (9.62%) 
Myalgia  1  92/325 (28.31%)  22/156 (14.10%) 
Arthralgia  1  63/325 (19.38%)  18/156 (11.54%) 
Back pain  1  35/325 (10.77%)  20/156 (12.82%) 
Pain in extremity  1  24/325 (7.38%)  16/156 (10.26%) 
Muscular weakness  1  16/325 (4.92%)  9/156 (5.77%) 
Musculoskeletal pain  1  14/325 (4.31%)  8/156 (5.13%) 
Nervous system disorders     
Neuropathy peripheral  1  64/325 (19.69%)  24/156 (15.38%) 
Dysgeusia  1  53/325 (16.31%)  25/156 (16.03%) 
Dizziness  1  46/325 (14.15%)  24/156 (15.38%) 
Peripheral sensory neuropathy  1  42/325 (12.92%)  27/156 (17.31%) 
Headache  1  33/325 (10.15%)  20/156 (12.82%) 
Paraesthesia  1  25/325 (7.69%)  17/156 (10.90%) 
Psychiatric disorders     
Insomnia  1  61/325 (18.77%)  17/156 (10.90%) 
Depression  1  22/325 (6.77%)  11/156 (7.05%) 
Anxiety  1  20/325 (6.15%)  11/156 (7.05%) 
Respiratory, thoracic and mediastinal disorders     
Dysphonia  1  48/325 (14.77%)  7/156 (4.49%) 
Dyspnoea  1  48/325 (14.77%)  17/156 (10.90%) 
Cough  1  46/325 (14.15%)  22/156 (14.10%) 
Epistaxis  1  43/325 (13.23%)  16/156 (10.26%) 
Hiccups  1  21/325 (6.46%)  15/156 (9.62%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  110/325 (33.85%)  59/156 (37.82%) 
Rash  1  28/325 (8.62%)  17/156 (10.90%) 
Dry skin  1  19/325 (5.85%)  8/156 (5.13%) 
Pruritus  1  19/325 (5.85%)  10/156 (6.41%) 
Erythema  1  14/325 (4.31%)  10/156 (6.41%) 
Rash maculo-papular  1  11/325 (3.38%)  10/156 (6.41%) 
Vascular disorders     
Hypotension  1  46/325 (14.15%)  20/156 (12.82%) 
Hypertension  1  23/325 (7.08%)  12/156 (7.69%) 
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
Due to the negative study outcome, development of PEGPH20 was terminated.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: VP, Medical, Regulatory and Drug Safety
Organization: Halozyme Therapeutics
Phone: 858-794-8889
EMail: medinfo@halozyme.com
Layout table for additonal information
Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT02715804    
Other Study ID Numbers: HALO-109-301
2015-004068-13 ( EudraCT Number )
First Submitted: March 17, 2016
First Posted: March 22, 2016
Results First Submitted: June 11, 2020
Results First Posted: July 14, 2020
Last Update Posted: July 14, 2020