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A Phase 2 Study of RO7490677 In Participants With Myelofibrosis

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: NCT01981850
Recruitment Status : Completed
First Posted : November 13, 2013
Results First Posted : January 5, 2022
Last Update Posted : January 5, 2022
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Primary Myelofibrosis
Polycythemia Vera
Post-Essential Thrombocythemia Myelofibrosis
Interventions Biological: RO7490677
Drug: Ruxolitinib
Enrollment 125
Recruitment Details A total of 125 participants were enrolled at sites in 8 different countries.
Pre-assignment Details One randomized participant in Stage 2 did not receive the study treatment, bringing the total number of treated participants to 124.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants who completed the main phase of treatment moved to the open label extension. They were treated with single agent PRM-151 at a dose of 10 mg/kg administered as an IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle. Participants who completed the main phase of treatment moved to the open label extension. They were treated with PRM-151 at a dose of 10 mg/kg administered as an IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle. Participants who completed 9 cycles of the originally assigned treatment could switch to the open label extension. Participants enrolled received PRM-151 at a dose of 10mg/kg Q4W on days 1, 3, and 5 of first cycle of the open label phase and Day 1 of each subsequent 28 day cycle.
Period Title: Main Phase Stage 1
Started 8 7 6 6 0 0 0 0 0 0
Completed [1] 5 5 4 6 0 0 0 0 0 0
Not Completed 3 2 2 0 0 0 0 0 0 0
Reason Not Completed
Death             2             0             0             0             0             0             0             0             0             0
Informed Consent Withdrawn             1             0             0             0             0             0             0             0             0             0
Lack of Efficacy             0             2             0             0             0             0             0             0             0             0
Various reasons             0             0             2             0             0             0             0             0             0             0
[1]
Main Study
Period Title: Main Phase Stage 2
Started 0 0 0 0 33 32 32 0 0 0
Completed [1] 0 0 0 0 20 16 15 0 0 0
Not Completed 0 0 0 0 13 16 17 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             6             5             7             0             0             0
Informed Consent Withdrawn             0             0             0             0             4             3             3             0             0             0
Lack of Efficacy             0             0             0             0             1             2             0             0             0             0
Various reasons             0             0             0             0             2             0             1             0             0             0
Progressive Disease             0             0             0             0             0             6             6             0             0             0
[1]
Main Study
Period Title: Open Label Extension (OLE)
Started [1] 0 0 0 0 0 0 0 13 5 48
Completed 0 0 0 0 0 0 0 1 0 0
Not Completed 0 0 0 0 0 0 0 12 5 48
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             2             1             8
Lack of Efficacy             0             0             0             0             0             0             0             4             1             19
Various reasons             0             0             0             0             0             0             0             3             1             3
Progressive Disease             0             0             0             0             0             0             0             3             2             9
Informed Consent Withdrawn             0             0             0             0             0             0             0             0             0             8
Lost to Follow-up             0             0             0             0             0             0             0             0             0             1
[1]
Continued in OLE
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W Total
Hide Arm/Group Description Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Total of all reporting groups
Overall Number of Baseline Participants 8 7 6 6 33 32 32 124
Hide Baseline Analysis Population Description
Stage 1 & Stage 2 reported separately.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 7 participants 6 participants 6 participants 0 participants 0 participants 0 participants 27 participants
64.3  (11.4) 70.7  (6.3) 66.0  (7.3) 66.2  (8.6) 66.7  (8.7)
[1]
Measure Description: Participants in the Main Phase Stage 1 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 1 reported separately from Main Phase Stage 2.
Age, Continuous   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 0 participants 0 participants 0 participants 0 participants 33 participants 32 participants 32 participants 97 participants
70.6  (7.1) 70.2  (6.5) 69.4  (8.9) 70.1  (7.5)
[1]
Measure Description: Participants in the Main Phase Stage 2 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 2 reported separately from Main Phase Stage 1.
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 6 participants 6 participants 0 participants 0 participants 0 participants 27 participants
Female
5
  62.5%
2
  28.6%
3
  50.0%
5
  83.3%
15
  55.6%
Male
3
  37.5%
5
  71.4%
3
  50.0%
1
  16.7%
12
  44.4%
[1]
Measure Description: Participants in the Main Phase Stage 1 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 1 reported separately from Main Phase Stage 2.
Sex: Female, Male   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 33 participants 32 participants 32 participants 97 participants
Female
16
  48.5%
8
  25.0%
11
  34.4%
35
  36.1%
Male
17
  51.5%
24
  75.0%
21
  65.6%
62
  63.9%
[1]
Measure Description: Participants in the Main Phase Stage 2 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 2 reported separately from Main Phase Stage 1.
Ethnicity (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 6 participants 6 participants 0 participants 0 participants 0 participants 27 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   3.7%
Not Hispanic or Latino
8
 100.0%
7
 100.0%
4
  66.7%
6
 100.0%
25
  92.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   3.7%
[1]
Measure Description: Participants in the Main Phase Stage 1 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 1 reported separately from Main Phase Stage 2.
Race (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 7 participants 6 participants 6 participants 0 participants 0 participants 0 participants 27 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   3.7%
Asian
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
1
   3.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  12.5%
0
   0.0%
1
  16.7%
0
   0.0%
2
   7.4%
White
7
  87.5%
7
 100.0%
3
  50.0%
6
 100.0%
23
  85.2%
More than one race
0
   0.0%
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%
0
   0.0%
[1]
Measure Description: Participants in the Main Phase Stage 1 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 1 reported separately from Main Phase Stage 2.
Race (NIH/OMB)   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants 0 participants 33 participants 32 participants 32 participants 97 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   3.1%
2
   6.3%
3
   3.1%
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%
1
   3.1%
0
   0.0%
1
   1.0%
White
33
 100.0%
29
  90.6%
29
  90.6%
91
  93.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
1
   3.1%
1
   3.1%
2
   2.1%
[1]
Measure Description: Participants in the Main Phase Stage 2 part of the study
[2]
Measure Analysis Population Description: Main Phase Stage 2 reported separately from Main Phase Stage 1.
1.Primary Outcome
Title Stage 1 Main Phase: Overall Response Rate (ORR)
Hide Description ORR was defined as the percent of participants with a response according to the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria. This was defined as those participants who achieved clinical improvement (CI), partial remission (PR), or complete remission (CR) at a post-baseline assessment of treatment response OR had at least stable disease (SD) for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease.
Time Frame Up until and including completion of 6 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population included all participants who received at least one dose of RO7490667.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
37.5
(11.11 to 71.08)
14.3
(0.73 to 52.07)
33.3
(6.28 to 72.87)
50.0
(15.32 to 84.68)
2.Primary Outcome
Title Stage 2 Main Phase: Bone Marrow Response Rate (BMRR)
Hide Description Response rate was defined as the percent of participants with a reduction in bone marrow fibrosis by at least one grade according to World Health Organization (WHO) criteria from baseline to any time during the study. This was determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy.
Time Frame Up until and including completion of 9 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
30.3
(14.62 to 45.98)
31.3
(15.19 to 47.31)
25.0
(10.00 to 40.00)
3.Primary Outcome
Title Stage 1 Main + Open-Label Extension (OLE): ORR
Hide Description ORR was defined as the percent of participants with a response according to the IWG-MRT criteria. This was defined as those participants who achieved CI, PR, or CR at a post-baseline assessment of treatment response OR had at least SD for three consecutive end-of-cycle response assessments (e.g. Day 1 of the subsequent cycle) in conjunction with improvement in the bone marrow fibrosis score relative to baseline by at least one grade at any time point during the period of stable disease. Participants who achieved a clinical benefit in the main phase had the opportunity to remain on treatment. The determination of ORR in the main phase is outlined in the arms description below. Participants who didn't achieve a benefit had the opportunity to switch to a different dosing schedule in the OLE phase. The determination of ORR in the OLE phase is outlined in the arms descriptions below.
Time Frame From cycle 1 day 1 up until cycle 6, day 29 (Main Phase). From cycle 7 day 1 up until study discontinuation or study termination, up to 83 cycles (OLE). Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population (main phase + OLE) included all participants who received at least one dose of RO7490667.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV QW; OLE: RO7490677 10 mg/kg IV Q4W Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib; OLE: RO7490677 10 mg/kg IV Q4W + Ruxo. Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib; OLE: RO7490677 10 mg/kg IV Q4W + Ruxo.
Hide Arm/Group Description:

Participants were followed through their originally assigned treatment. If a participant achieved a clinical benefit in the main phase, they had the opportunity to remain on treatment. Participants who didn't achieve a clinical benefit had the opportunity to switch to a different dosing schedule in the OLE phase. Participants were not allowed to add ruxolitinib if they had been receiving monotherapy during the main phase.

Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for 6 cycles (main phase) and on Days 1, 3, and 5 of Cycle 7 and Day 1 of each subsequent 28 day cycle for 83 cycles (OLE).

Participants were followed through their originally assigned treatment. If a participant achieved a clinical benefit in the main phase, they had the opportunity to remain on treatment. Participants who didn't achieve a clinical benefit had the opportunity to switch to a different dosing schedule in the OLE phase. Participants were not allowed to add ruxolitinib if they had been receiving monotherapy during the main phase.

Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for 6 cycles (main phase) and on Days 1, 3, and 5 of Cycle 7 and Day 1 of each subsequent 28 day cycle for 83 cycles (OLE).

Participants were followed through their originally assigned treatment. If a participant achieved a clinical benefit in the main phase, they had the opportunity to remain on treatment. Participants who didn't achieve a clinical benefit had the opportunity to switch to a different dosing schedule in the OLE phase. Participants could drop ruxolitinib in the OLE, but were not allowed to add ruxolitinib if they had been receiving monotherapy during the main phase.

Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for 6 cycles (main phase) and on Days 1, 3, and 5 of Cycle 7 and Day 1 of each subsequent 28 day cycle for 83 cycles (OLE).

Participants were followed through their originally assigned treatment. If a participant achieved a clinical benefit in the main phase, they had the opportunity to remain on treatment. Participants who didn't achieve a clinical benefit had the opportunity to switch to a different dosing schedule in the OLE phase. Participants could drop ruxolitinib in the OLE, but were not allowed to add ruxolitinib if they had been receiving monotherapy during the main phase.

Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for 6 cycles (main phase) and on Days 1, 3, and 5 of Cycle 7 and Day 1 of each subsequent 28 day cycle for 83 cycles (OLE).

Overall Number of Participants Analyzed 8 7 6 6
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: Percentage of Participants
50.0
(19.29 to 80.71)
71.4
(34.13 to 94.66)
50.0
(15.32 to 84.68)
66.7
(27.13 to 93.72)
4.Primary Outcome
Title Stage 2 Main + Open-Label Extension (OLE): BMRR
Hide Description Defined as the percent of participants with a reduction in bone marrow fibrosis score by at least one grade according to WHO criteria at any time during the study. As determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy. Participants in the main phase had the opportunity to remain on treatment (as outlined in the arms description below). Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment and receive PRM-151 10 mg/kg/Q4W (as outlined in the arms description below).
Time Frame From cycle 1 day 1 up until cycle 9 day 29 (main phase). From cycle 10 day 1 up until study discontinuation or study termination, up to 51 cycles (OLE). Each cycle is 28 days.
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Hide Analysis Population Description
The all treated population (main phase + OLE) included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W; OLE: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:

Participants were followed through their originally assigned treatment. Participants in the main phase had the opportunity to remain on treatment. Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment as outlined below.

Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for 9 cycles (main phase) and PRM-151 at a dose of 10 mg/kg on Days 1, 3, and 5 of Cycle 10 and Day 1 of each subsequent 28 day cycle for 51 cycles (OLE).

Participants were followed through their originally assigned treatment. Participants in the main phase had the opportunity to remain on treatment. Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment as outlined below.

Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for 9 cycles (main phase) and PRM-151 at a dose of 10 mg/kg on Days 1, 3, and 5 of Cycle 10 and Day 1 of each subsequent 28 day cycle for 51 cycles (OLE).

Participants were followed through their originally assigned treatment. Participants in the main phase had the opportunity to remain on treatment. Participants also had the option to switch to the OLE phase after completing 9 cycles of the originally assigned treatment as outlined below.

Participants enrolled received PRM-151 at a dose of 10mg/kg Q4W on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for 9 cycles (main phase) and on Days 1, 3, and 5 of Cycle 10 and Day 1 of each subsequent 28 day cycle for 51 cycles (OLE).

Overall Number of Participants Analyzed 33 32 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
30.3
(14.62 to 45.98)
34.4
(17.92 to 50.83)
25.0
(10.00 to 40.00)
5.Secondary Outcome
Title Stage 1 Main Phase: BMRR
Hide Description Bone marrow response was defined as a reduction in bone marrow fibrosis score by at least one grade from baseline at anytime during the study.
Time Frame Baseline, Weeks 12 and 24
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Hide Analysis Population Description
The all treated population included all participants who received at least one dose of RO7490667.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
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Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
37.5
(3.95 to 71.05)
14.3
(0.00 to 40.21)
16.7
(0.00 to 46.49)
50.0
(9.99 to 90.01)
6.Secondary Outcome
Title Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes
Hide Description The MPN-SAF TSS total symptom score was the sum of the following 10 items: Filling up quickly when you eat (early satiety), abdominal discomfort, inactivity, Problems with concentration, Worst fatigue, Night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months. The MPN-SAF Total Symptom Score had a possible range of 0 to 100, where a lower score was more favorable. The values reported are the change from baseline scores.
Time Frame Baseline, beginning of each cycle (Cycle 2 onward). Each cycle is 28 days.
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Hide Analysis Population Description
The all treated population included all participants who received at least one dose of RO7490667.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Baseline Number Analyzed 8 participants 7 participants 6 participants 6 participants
23.1  (19.1) 16.9  (7.2) 26.8  (17.1) 15.3  (10.4)
Cycle(C)2 Day(D)1 Number Analyzed 7 participants 6 participants 6 participants 6 participants
-5.3  (12.6) 5.7  (11.8) 0.5  (8.8) -2.0  (5.0)
C3D1 Number Analyzed 7 participants 7 participants 6 participants 5 participants
-9.1  (10.9) 1.9  (5.3) -2.7  (14.8) 4.2  (8.0)
C4D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
-8.7  (10.7) 1.0  (8.0) -7.5  (6.0) 5.7  (20.9)
C5D1 Number Analyzed 5 participants 7 participants 6 participants 6 participants
-13.2  (13.2) 2.6  (6.9) -6.7  (10.6) 1.5  (13.6)
C6D1 Number Analyzed 5 participants 5 participants 5 participants 6 participants
-12.2  (9.5) -0.8  (8.3) -5.4  (6.2) 4.3  (11.5)
C6D29 Number Analyzed 5 participants 5 participants 4 participants 4 participants
-15.0  (13.7) -2.2  (5.3) -5.3  (4.6) 2.3  (8.8)
7.Secondary Outcome
Title Stage 2 Main Phase: BMRR
Hide Description Response rate was defined as the percent of participants with a reduction in bone marrow fibrosis by at least one grade according to World Health Organization (WHO) criteria at any time during the study. This was determined by a central adjudication panel of expert hematopathologists, blinded to participant, treatment, and time of biopsy.
Time Frame Up until and including completion of 9 cycles. Each cycle is 28 days.
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Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
30.3
(14.62 to 45.98)
31.3
(15.19 to 47.31)
25.0
(10.0 to 40.00)
8.Secondary Outcome
Title Stage 2 Main Phase: BMRR - Reduction of Bone Marrow Fibrosis by Visit
Hide Description Reduction in bone marrow fibrosis score: Reduction of at least one grade from baseline. Bone marrow fibrosis grades according to WHO criteria (as determined by central adjudication).
Time Frame Day 1 on Cycles 4, 7, 10 and Cycle 9 Day 29. Each cycle is 28 days.
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Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Number
Unit of Measure: Percentage of Participants
Cycle(C) 4 Day(D) 1 Number Analyzed 28 participants 25 participants 26 participants
10.7 24.0 19.2
C7D1 Number Analyzed 21 participants 17 participants 19 participants
23.8 11.8 10.5
C9D29/C10D1 Number Analyzed 20 participants 14 participants 15 participants
30.0 21.4 13.3
9.Secondary Outcome
Title Stage 2 Main Phase: Duration of Bone Marrow Improvement
Hide Description Duration of response was defined as time from first decrease from baseline >= 1 grade to time of return to baseline levels.
Time Frame From first decrease from baseline of one grade to time of return to baseline levels, up to cycle 9 of 28-day cycles.
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Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Median (95% Confidence Interval)
Unit of Measure: Weeks
NA [1] 
(12.0 to NA)
12.0 [1] 
(12.0 to NA)
12.1
(11.4 to 13.0)
[1]
Data was not evaluable as the participants who had bone marrow improvement but did not return to baseline levels at the end of main phase were censored at their last bone marrow assessment in the main phase (the last timepoint in the main phase at which the improvement was still observed).
10.Secondary Outcome
Title Stage 2 Main Phase: Hemoglobin Improvement
Hide Description Hemoglobin improvement was measured by the percent of participants with: Red cell transfusion independence (no transfusions for >= 12 consecutive weeks) OR 50% reduction in red blood cell (RBC) transfusions for >= 12 consecutive weeks OR percent of participants with >= 10 g/L and >= 20 g/L increase in hemoglobin for >= 12 consecutive weeks without transfusions (outcome parameter assessed was dependent on baseline hemoglobin/transfusion status).
Time Frame Up until and including completion of 9 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Number
Unit of Measure: Percentage of Participants
15.2 15.6 6.3
11.Secondary Outcome
Title Stage 2 Main Phase: Platelet Improvement
Hide Description Platelet improvement was measured by the percent of participants with: Platelet transfusion independence (no transfusions for >= 12 consecutive weeks) OR 50% reduction in platelets transfusions for >= 12 consecutive weeks OR doubling of baseline platelet count for >= 12 consecutive weeks without platelet transfusions OR platelet count > 50 x 10e9/L for >=12 consecutive weeks without platelet transfusions OR doubling of baseline platelet count for >= 12 consecutive weeks without platelet transfusions OR platelet count > 25 x 10e9/L for >= 12 consecutive weeks without platelet transfusions (outcome parameter assessed is dependent on baseline platelet status).
Time Frame Up until and including completion of 9 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Number
Unit of Measure: Percentage of Participants
27.3 34.4 37.5
12.Secondary Outcome
Title Stage 2 Main Phase: Symptom Improvement
Hide Description Symptom improvement was assessed as the percent of participants with 50% reduction in MPN-SAF TSS from baseline over time. The MPN-SAF TSS total symptom score was the sum of the following 10 items: Filling up quickly when you eat (early satiety), abdominal discomfort, inactivity, Problems with concentration, Worst fatigue, Night sweats, Itching, Bone pain, Fever and Unintentional weight loss last 6 months. The MPN-SAF Total Symptom Score had a possible range of 0 to 100, where a lower score was more favorable.
Time Frame Up until and including completion of 9 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Count of Participants
Unit of Measure: Participants
Cycle(C) 2 Day(D) 1 Number Analyzed 31 participants 31 participants 29 participants
5
  16.1%
2
   6.5%
1
   3.4%
C3D1 Number Analyzed 30 participants 29 participants 28 participants
6
  20.0%
3
  10.3%
2
   7.1%
C4D1 Number Analyzed 28 participants 29 participants 28 participants
3
  10.7%
4
  13.8%
2
   7.1%
C5D1 Number Analyzed 24 participants 25 participants 25 participants
5
  20.8%
2
   8.0%
1
   4.0%
C6D1 Number Analyzed 23 participants 21 participants 25 participants
8
  34.8%
3
  14.3%
3
  12.0%
C7D1 Number Analyzed 21 participants 18 participants 20 participants
8
  38.1%
5
  27.8%
0
   0.0%
C8D1 Number Analyzed 20 participants 18 participants 19 participants
5
  25.0%
3
  16.7%
0
   0.0%
C9D1 Number Analyzed 21 participants 17 participants 17 participants
5
  23.8%
3
  17.6%
1
   5.9%
C9D29/C10D1 Number Analyzed 20 participants 16 participants 13 participants
5
  25.0%
2
  12.5%
0
   0.0%
13.Secondary Outcome
Title Stage 2 Main Phase: Percentage of Participants With Complete Response (CR), Partial Response (PR), Clinical Improvement (CI), Stable Disease (SD), and Progressive Disease (PD) According to IWG-MRT Criteria
Hide Description Best Overall Response: (CR, PR, CI), SD and PD according to the IWG-MRT Criteria.
Time Frame Up until and including completion of 9 cycles. Each cycle is 28 days.
Hide Outcome Measure Data
Hide Analysis Population Description
The all treated population included all participants randomized and who received at least one administration of the drug.
Arm/Group Title Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Overall Number of Participants Analyzed 33 32 32
Measure Type: Count of Participants
Unit of Measure: Participants
CR
0
   0.0%
0
   0.0%
0
   0.0%
PR
0
   0.0%
0
   0.0%
0
   0.0%
CI
8
  24.2%
6
  18.8%
2
   6.3%
SD
20
  60.6%
21
  65.6%
26
  81.3%
PD
3
   9.1%
3
   9.4%
4
  12.5%
Not evaluable
2
   6.1%
2
   6.3%
0
   0.0%
14.Other Pre-specified Outcome
Title Stage 1 Main Phase: Maximum Drug Concentration (Cmax)
Hide Description Cmax is the maximum observed RO7490677 plasma concentration.
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
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Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Micrograms per Milliliter (ug/mL)
C1D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
133
(48.4%)
113
(28.1%)
164
(23.9%)
112
(90.4%)
C1D15 Number Analyzed 7 participants 0 participants 6 participants 0 participants
127
(31.9%)
126
(27.5%)
C2D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
107
(26.9%)
110
(20.9%)
149
(29.1%)
130
(80.2%)
C6D1 Number Analyzed 5 participants 5 participants 5 participants 6 participants
142
(70.0%)
111
(28.0%)
136
(34.1%)
142
(27.4%)
15.Other Pre-specified Outcome
Title Stage 1 Main Phase: Time to Maximum Concentration (Tmax)
Hide Description Time at which the maximum plasma concentration was observed.
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Median (Full Range)
Unit of Measure: Hour (hr)
C1D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
1.12
(1.00 to 2.00)
1.10
(1.00 to 2.08)
1.14
(1.00 to 2.25)
1.13
(1.00 to 5.00)
C1D15 Number Analyzed 7 participants 0 participants 6 participants 0 participants
1.13
(1.03 to 1.80)
1.65
(1.02 to 2.50)
C2D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
1.10
(1.00 to 3.17)
1.08
(1.03 to 1.08)
1.05
(1.00 to 1.32)
1.44
(1.00 to 9.00)
C6D1 Number Analyzed 5 participants 5 participants 5 participants 6 participants
2.00
(1.03 to 5.20)
1.07
(1.00 to 2.03)
1.17
(1.05 to 5.00)
1.01
(1.00 to 1.08)
16.Other Pre-specified Outcome
Title Stage 1 Main Phase: Area Under the Curve up to the Last Measurable Concentration (AUC0-last)
Hide Description Area under the plasma concentration time curve from time 0 to time of last measurable plasma concentration.
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug*hour/mL
C1D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
1810
(72.0%)
1690
(26.1%)
2590
(28.7%)
1500
(158.3%)
C1D15 Number Analyzed 7 participants 0 participants 6 participants 0 participants
1460
(142.0%)
2590
(187.6%)
C2D1 Number Analyzed 7 participants 7 participants 6 participants 6 participants
127.3
(904%)
504
(84.7%)
2990
(92.0%)
663
(79.5%)
C6D1 Number Analyzed 5 participants 5 participants 5 participants 6 participants
698
(63.0%)
570
(44.8%)
764
(28.9%)
703
(33.8%)
17.Other Pre-specified Outcome
Title Stage 1 Main Phase: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf)
Hide Description Area under the plasma concentration-time curve from 0-time extrapolated to infinity.
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ug*hour/mL
C1D1 Number Analyzed 3 participants 7 participants 5 participants 3 participants
2830
(12.9%)
2050
(29.5%)
2970
(34.9%)
3130
(8.6%)
C1D15 Number Analyzed 4 participants 0 participants 4 participants 0 participants
3450
(2.8%)
6060
(23.2%)
C2D1 Number Analyzed 3 participants 0 participants 5 participants 0 participants
2170
(170.9%)
4230
(34.8%)
C6D1 Number Analyzed 0 participants 0 participants 1 participants 0 participants
819 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated from data for a single participant.
18.Other Pre-specified Outcome
Title Stage 1 Main Phase: Terminal Elimination Half-Life (T1/2)
Hide Description Apparent terminal elimination half-life of RO7490677.
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr
C1D1 Number Analyzed 3 participants 7 participants 5 participants 3 participants
14.7
(19.2%)
17.2
(23.7%)
16.8
(17.7%)
18.4
(7.9%)
C1D15 Number Analyzed 4 participants 0 participants 4 participants 0 participants
31.2
(45.0%)
40.4
(12.6%)
C2D1 Number Analyzed 3 participants 0 participants 5 participants 0 participants
18.0
(220.6%)
30.0
(48.6%)
C6D1 Number Analyzed 0 participants 0 participants 1 participants 0 participants
1.95 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated from data for a single participant.
19.Other Pre-specified Outcome
Title Stage 1 Main Phase: Clearance (CL)
Hide Description [Not Specified]
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Litres per hour (L/hr)
C1D1 Number Analyzed 3 participants 7 participants 5 participants 3 participants
0.258
(9.0%)
0.362
(31.5%)
0.269
(32.9%)
0.233
(33.3%)
C1D15 Number Analyzed 4 participants 0 participants 4 participants 0 participants
0.233
(24.9%)
0.147
(35.0%)
C2D1 Number Analyzed 3 participants 0 participants 5 participants 0 participants
0.382
(229.9%)
0.189
(55.5%)
C6D1 Number Analyzed 0 participants 0 participants 1 participants 0 participants
1.42 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated from data for a single participant.
20.Other Pre-specified Outcome
Title Stage 1 Main Phase: Volume of Distribution (Vd)
Hide Description [Not Specified]
Time Frame Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all participants who received at least one dose of rhPTX-2 and had at least one post-dose total PTX-2 concentration result.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Overall Number of Participants Analyzed 8 7 6 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Litres (L)
C1D1 Number Analyzed 3 participants 7 participants 5 participants 3 participants
5.47
(10.9%)
9.00
(28.8%)
6.52
(26.4%)
6.17
(38.9%)
C1D15 Number Analyzed 4 participants 0 participants 4 participants 0 participants
10.5
(62.4%)
8.57
(47.6%)
C2D1 Number Analyzed 3 participants 0 participants 5 participants 0 participants
9.93
(63.0%)
8.18
(24.5%)
C6D1 Number Analyzed 0 participants 0 participants 1 participants 0 participants
4.01 [1] 
(NA%)
[1]
Geometric Coefficient of Variation could not be calculated from data for a single participant.
21.Other Pre-specified Outcome
Title Percentage of Participants With Adverse Events (AEs) and Infusion Related Reactions (IRRs)
Hide Description An AE was defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related. Pre-existing conditions which worsened during the study were also considered as adverse events. IRRs were considerd to be Adverse Events of Special Interest (AESI). Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0.
Time Frame Baseline up until 6.75 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study drug.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) OLE Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants who completed 9 cycles of the originally assigned treatment could switch to the open label extension. Participants enrolled received PRM-151 at a dose of 10mg/kg Q4W on days 1, 3, and 5 of first cycle of the open label phase and Day 1 of each subsequent 28 day cycle.
Overall Number of Participants Analyzed 8 7 6 6 33 32 32 13 5 48
Measure Type: Number
Unit of Measure: Percentage of Participants
AEs 100 85.7 100 100 100 100 100 92.3 100 89.6
IRRs 0 0 0 16.7 3.0 3.1 6.3 7.7 20.0 2.1
22.Other Pre-specified Outcome
Title Percentage of Participants With Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation
Hide Description An SAE was defined as any AE that occurred at any dose the resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalizations; a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly or birth defect. An AE was defined as any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related. Pre-existing conditions which worsened during the study were also considered as adverse events. Grading was completed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0.
Time Frame Baseline up until 6.75 years
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population included all participants who received at least one dose of study drug.
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) OLE Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description:
Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles.
Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles.
Participants who completed 9 cycles of the originally assigned treatment could switch to the open label extension. Participants enrolled received PRM-151 at a dose of 10mg/kg Q4W on days 1, 3, and 5 of first cycle of the open label phase and Day 1 of each subsequent 28 day cycle.
Overall Number of Participants Analyzed 8 7 6 6 33 32 32 13 5 48
Measure Type: Number
Unit of Measure: Percentage of Participants
SAEs 25.0 0 0 0 15.2 15.6 28.1 7.7 0 22.9
AEs 25.0 0 0 0 21.2 34.4 37.5 30.8 0 27.1
Time Frame Baseline up until 6.75 years
Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs) were defined as any AE that occurred after the administration of any amount of the study drug, or any event that was present at baseline.
 
Arm/Group Title Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Hide Arm/Group Description Participants who received no treatment for Myelofibrosis (MF) in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 milligram per kilogram (mg/kg) administered as a 30 minute intravenous (IV) infusion on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Participants who received no treatment for MF in at least two weeks were assigned to treatment with single agent PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, 5, 8, 15, and 22 of Cycle 1 and Days 1, 8, 15 and 22 of each subsequent 28 day cycle for six cycles. Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks were assigned to receive PRM-151 at a dose of 10 mg/kg administered as a 30 minute IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. Participants were treated with single agent PRM-151 at a dose of 0.3 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants were treated with single agent PRM-151 at a dose of 3.0 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants were treated with single agent PRM-151 at a dose of 10 mg/kg administered as a 60 minute IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. Participants who completed the main phase of treatment moved to the open label extension. They were treated with single agent PRM-151 at a dose of 10 mg/kg administered as an IV infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle. Participants who completed the main phase of treatment moved to the open label extension. They were treated with PRM-151 at a dose of 10 mg/kg administered as an IV infusion in combination with daily oral ruxolitinib on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle. Participants who completed 9 cycles of the originally assigned treatment could switch to the open label extension. Participants enrolled received PRM-151 at a dose of 10mg/kg Q4W on days 1, 3, and 5 of first cycle of the open label phase and Day 1 of each subsequent 28 day cycle.
All-Cause Mortality
Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/8 (25.00%)      0/7 (0.00%)      1/6 (16.67%)      0/6 (0.00%)      7/33 (21.21%)      6/32 (18.75%)      9/32 (28.13%)      0/13 (0.00%)      0/5 (0.00%)      7/48 (14.58%)    
Hide Serious Adverse Events
Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/8 (25.00%)      1/7 (14.29%)      2/6 (33.33%)      0/6 (0.00%)      11/33 (33.33%)      14/32 (43.75%)      14/32 (43.75%)      5/13 (38.46%)      2/5 (40.00%)      22/48 (45.83%)    
Blood and lymphatic system disorders                     
Anaemia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 2/48 (4.17%)  2
Bone marrow failure  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Extramedullary haemopoiesis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Leukocytosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Pancytopenia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Thrombocytopenia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Cardiac disorders                     
Acute coronary syndrome  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Acute myocardial infarction  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Aortic valve stenosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Cardiac failure  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  3 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Cardiopulmonary failure  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Coronary artery disease  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Pericardial effusion  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Cardiac arrest  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Gastrointestinal disorders                     
Abdominal pain  1  0/8 (0.00%)  0 1/7 (14.29%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Femoral hernia, obstructive  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Intestinal ischaemia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Melaena  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Oesophageal varices haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  2
Rectal haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Varices oesophageal  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Intestinal obstruction  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Mouth haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Upper gastrointestinal haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 1/5 (20.00%)  2 0/48 (0.00%)  0
General disorders                     
Asthenia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Chest pain  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Death  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Disease progression  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  2 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Inflammation  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Peripheral swelling  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Unevaluable event  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  2
Organ failure  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Hepatobiliary disorders                     
Cholecystitis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Cholecystitis acute  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Cholelithiasis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Portal hypertension  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Immune system disorders                     
Anaphylactic reaction  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Infections and infestations                     
Infection  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 1/5 (20.00%)  1 1/48 (2.08%)  1
Pneumonia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 2/33 (6.06%)  3 1/32 (3.13%)  1 2/32 (6.25%)  2 0/13 (0.00%)  0 1/5 (20.00%)  2 3/48 (6.25%)  3
Abscess limb  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Cellulitis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Endocarditis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Influenza  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Intervertebral discitis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Osteomyelitis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 2/48 (4.17%)  2
Pneumonia fungal  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Pseudomonal sepsis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Sepsis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Septic shock  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Upper respiratory tract infection  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Urinary tract infection  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Urosepsis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  3 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Enterocolitis infectious  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 1/5 (20.00%)  1 0/48 (0.00%)  0
Gastroenteritis  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Pneumonia viral  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Respiratory syncytial virus infection  1  0/8 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Sialoadenitis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Wound infection  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 1/5 (20.00%)  1 0/48 (0.00%)  0
Injury, poisoning and procedural complications                     
Fall  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Infusion related reaction  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Osteoradionecrosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Procedural haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Subdural haematoma  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Multiple fractures  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Post procedural haematoma  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Rib fracture  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Investigations                     
Eastern Cooperative Oncology Group performance status worsened  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Hepatic enzyme increased  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Metabolism and nutrition disorders                     
Cachexia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Hyperkalaemia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Hyperuricaemia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Musculoskeletal and connective tissue disorders                     
Back pain  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Chondrocalcinosis pyrophosphate  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Haemarthrosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Haematoma muscle  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Joint effusion  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                     
Acute myeloid leukaemia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Malignant neoplasm progression  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Myelofibrosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 2/48 (4.17%)  2
Primary myelofibrosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Transformation to acute myeloid leukaemia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Hepatic cancer  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Metastatic squamous cell carcinoma  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Squamous cell carcinoma  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 1/5 (20.00%)  2 0/48 (0.00%)  0
Nervous system disorders                     
Cerebral haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Hepatic encephalopathy  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Subarachnoid haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Syncope  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Metabolic encephalopathy  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Renal and urinary disorders                     
Acute kidney injury  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  2
Nephrolithiasis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Renal failure  1  1/8 (12.50%)  1 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Urinary bladder haemorrhage  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  3 0/5 (0.00%)  0 0/48 (0.00%)  0
Urinary bladder rupture  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
Respiratory, thoracic and mediastinal disorders                     
Chronic obstructive pulmonary disease  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Epistaxis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/33 (6.06%)  2 1/32 (3.13%)  1 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Pleural effusion  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Skin and subcutaneous tissue disorders                     
Eczema  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Skin ulcer  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Surgical and medical procedures                     
Aortic valve replacement  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Vascular disorders                     
Dry gangrene  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Haematoma  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 1/13 (7.69%)  1 0/5 (0.00%)  0 0/48 (0.00%)  0
1
Term from vocabulary, MedDRA version 23.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Main Phase Stage 1: RO7490677 10 mg/kg IV Every Week (QW) Main Phase Stage 1: RO7490677 10 mg/kg IV Every 4 Weeks (Q4W) Main Phase Stage 1: RO7490677 10 mg/kg IV QW + Ruxolitinib Main Phase Stage 1: RO7490677 10 mg/kg IV Q4W+ Ruxolitinib Main Phase Stage 2: RO7490677 0.3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 3 mg/kg IV Q4W Main Phase Stage 2: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W OLE Stage 1: RO7490677 10 mg/kg IV Q4W + Ruxolitinib OLE Stage 2: RO7490677 10 mg/kg IV Q4W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/8 (100.00%)      6/7 (85.71%)      6/6 (100.00%)      6/6 (100.00%)      32/33 (96.97%)      30/32 (93.75%)      31/32 (96.88%)      12/13 (92.31%)      5/5 (100.00%)      32/48 (66.67%)    
Blood and lymphatic system disorders                     
Anaemia  1  1/8 (12.50%)  1 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 5/33 (15.15%)  11 6/32 (18.75%)  8 3/32 (9.38%)  6 1/13 (7.69%)  2 1/5 (20.00%)  1 6/48 (12.50%)  12
Leukocytosis  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 1/5 (20.00%)  1 0/48 (0.00%)  0
Splenomegaly  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/33 (6.06%)  2 2/32 (6.25%)  3 2/32 (6.25%)  3 3/13 (23.08%)  3 0/5 (0.00%)  0 7/48 (14.58%)  7
Thrombocytopenia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 5/33 (15.15%)  6 4/32 (12.50%)  5 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 2/48 (4.17%)  3
Leukopenia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 2/32 (6.25%)  2 1/32 (3.13%)  1 0/13 (0.00%)  0 0/5 (0.00%)  0 1/48 (2.08%)  1
Neutropenia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 2/32 (6.25%)  3 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 2/48 (4.17%)  2
Increased tendency to bruise  1  0/8 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Cardiac disorders                     
Tachycardia  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/33 (3.03%)  1 2/32 (6.25%)  2 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Palpitations  1  0/8 (0.00%)  0 0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 0/5 (0.00%)  0 0/48 (0.00%)  0
Supraventricular extrasystoles  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 0/33 (0.00%)  0 0/32 (0.00%)  0 0/32 (0.00%)  0 0/13 (0.00%)  0 1/5 (20.00%)  1 0/48 (0.00%)  0
Endocrine disorders                     
Hypothyroidism  1  0/8 (0.00%)  0 0/7 (0.00%)  0 0/6 (0.00%)