A Phase 2 Study of RO7490677 In Participants With Myelofibrosis
Study Details
Study Description
Brief Summary
RO7490677 is an investigational drug that is being developed for possible use in the treatment of myelofibrosis (MF), a disease in which the bone marrow, which is the organ in the body that makes blood cells, is replaced by fibrosis, or excess scar tissue.
The purpose of this study is to gather information on whether RO7490677 has an effect on the MF disease, whether it is safe in patients with MF, and how well it is tolerated.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
Stage 1 of this study has completed. Stage 1 was an open-label, Simon two stage, Phase 2 study to determine the efficacy and safety of two different dose schedules of RO7490677 in participants with PMF and post ET/PV MF. There were two treatment cohorts, each assigned to one of two dose schedules receiving either single-agent RO7490677 or RO7490677 in combination with ruxolitinib. Participants were assigned to a weekly or every four week dosing schedule by the investigator.
Stage 2 is a randomized, double-blind Phase 2 study to determine the efficacy and safety of three different doses of RO7490677 in participants with PMF and post ET/PV MF. Participants will be randomized to one of three doses: 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg of RO7490677. This is the second stage of an adaptive design study as defined in FDA Draft Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics, February 2010. Modifications to dose levels, schedule, and regimen have been made in Stage 2 based on data from Stage 1.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Stage 1: Cohort 1 Weekly Participants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg IV 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. |
Biological: RO7490677
IV infusion
Other Names:
|
Experimental: Stage 1: Cohort 1 Every 4 Weeks Paricipants who received no treatment for MF in at least two weeks will be assigned to treatment with single agent RO7490677 at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. |
Biological: RO7490677
IV infusion
Other Names:
|
Experimental: Stage 1: Cohort 2 Weekly Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV 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. |
Biological: RO7490677
IV infusion
Other Names:
Drug: Ruxolitinib
IV infusion
Other Names:
|
Experimental: Stage 1: Cohort 2 Every 4 Weeks Participants on a stable dose of ruxolitinib for at least 12 weeks, with no improvement in spleen during the last four weeks will be assigned to receive RO7490677 in combination with ruxolitinib at a dose of 10 mg/kg administered IV on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for six cycles. |
Biological: RO7490677
IV infusion
Other Names:
Drug: Ruxolitinib
IV infusion
Other Names:
|
Experimental: Stage 2: Cohort 1 0.3mg/kg Every 4 Weeks Participants will be treated with single agent RO7490677 at a dose of 0.3 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. |
Biological: RO7490677
IV infusion
Other Names:
|
Experimental: Stage 2: Cohort 2 3mg/kg Every 4 Weeks Participants will be treated with single agent RO7490677 at a dose of 3.0 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. |
Biological: RO7490677
IV infusion
Other Names:
|
Experimental: Stage 2: Cohort 3 10mg /kg Every 4 Weeks Participants will be treated with single agent RO7490677 at a dose of 10 mg/kg IV administered as a 60 minute intravenous infusion on Days 1, 3, and 5 of Cycle 1 and Day 1 of each subsequent 28 day cycle for nine cycles. |
Biological: RO7490677
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Stage 1 Main Phase: Overall Response Rate (ORR) [Up until and including completion of 6 cycles. Each cycle is 28 days.]
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.
- Stage 2 Main Phase: Bone Marrow Response Rate (BMRR) [Up until and including completion of 9 cycles. Each cycle is 28 days.]
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.
- Stage 1 Main + Open-Label Extension (OLE): ORR [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.]
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.
- Stage 2 Main + Open-Label Extension (OLE): BMRR [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.]
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).
Secondary Outcome Measures
- Stage 1 Main Phase: BMRR [Baseline, Weeks 12 and 24]
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.
- Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes [Baseline, beginning of each cycle (Cycle 2 onward). Each cycle is 28 days.]
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.
- Stage 2 Main Phase: BMRR [Up until and including completion of 9 cycles. Each cycle is 28 days.]
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.
- Stage 2 Main Phase: BMRR - Reduction of Bone Marrow Fibrosis by Visit [Day 1 on Cycles 4, 7, 10 and Cycle 9 Day 29. Each cycle is 28 days.]
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).
- Stage 2 Main Phase: Duration of Bone Marrow Improvement [From first decrease from baseline of one grade to time of return to baseline levels, up to cycle 9 of 28-day cycles.]
Duration of response was defined as time from first decrease from baseline >= 1 grade to time of return to baseline levels.
- Stage 2 Main Phase: Hemoglobin Improvement [Up until and including completion of 9 cycles. Each cycle is 28 days.]
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).
- Stage 2 Main Phase: Platelet Improvement [Up until and including completion of 9 cycles. Each cycle is 28 days.]
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).
- Stage 2 Main Phase: Symptom Improvement [Up until and including completion of 9 cycles. Each cycle is 28 days.]
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.
- 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 [Up until and including completion of 9 cycles. Each cycle is 28 days.]
Best Overall Response: (CR, PR, CI), SD and PD according to the IWG-MRT Criteria.
Other Outcome Measures
- Stage 1 Main Phase: Maximum Drug Concentration (Cmax) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
Cmax is the maximum observed RO7490677 plasma concentration.
- Stage 1 Main Phase: Time to Maximum Concentration (Tmax) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
Time at which the maximum plasma concentration was observed.
- Stage 1 Main Phase: Area Under the Curve up to the Last Measurable Concentration (AUC0-last) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
Area under the plasma concentration time curve from time 0 to time of last measurable plasma concentration.
- Stage 1 Main Phase: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
Area under the plasma concentration-time curve from 0-time extrapolated to infinity.
- Stage 1 Main Phase: Terminal Elimination Half-Life (T1/2) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
Apparent terminal elimination half-life of RO7490677.
- Stage 1 Main Phase: Clearance (CL) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
- Stage 1 Main Phase: Volume of Distribution (Vd) [Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days]
- Percentage of Participants With Adverse Events (AEs) and Infusion Related Reactions (IRRs) [Baseline up until 6.75 years]
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.
- Percentage of Participants With Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation [Baseline up until 6.75 years]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants must be ≥18 years of age at the time of signing the Informed Consent Form (ICF);
-
Participants must voluntarily sign an ICF;
-
Participants must have a pathologically confirmed diagnosis of PMF as per the WHO diagnostic criteria or post ET/PV MF;
-
At least Grade 2 marrow fibrosis according to the WHO Grading of Bone Marrow Fibrosis;
-
Intermediate-1, intermediate -2, or high risk disease according to the IWG -MRT Dynamic International Prognostic Scoring System
-
A bone marrow biopsy must be performed within four weeks prior to Cycle 1 Day 1 treatment to establish the baseline fibrosis score;
-
Participants must not be candidates for ruxolitinib based on EITHER:
-
Platelet count < 50 x 10e9/L, OR
-
Hgb < 100 g/L, have received ≥ 2 units PRBC in the 12 weeks prior to study entry, and be intolerant of or had inadequate response to ruxolitinib;
-
Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2. (Appendix F);
-
Life expectancy of at least twelve months;
-
At least four weeks must have elapsed between the last dose of any MF- directed drug treatments for myelofibrosis (including investigational therapies) and study enrollment;
-
Recovery to ≤ Grade 1 or baseline of any toxicities due to prior systemic treatments, excluding alopecia;
-
Women of child bearing potential (WCBP), defined as a sexually mature woman not surgically sterilized or not post-menopausal for at least 24 consecutive months if ≤55 years or 12 months if >55 years, must have a negative serum pregnancy test within four weeks prior to the first dose of study drug and must agree to use adequate methods of birth control throughout the study. Adequate methods of contraception are outlined in the protocol.
-
Ability to adhere to the study visit schedule and all protocol requirements;
-
Must have adequate organ function as demonstrated by the following:
-
ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
-
Direct bilirubin ≤ 1.5 x ULN; or ≤ 2x ULN (if upon judgment of the treating physician, it is believed to be due to EMH related to MF);
-
Serum creatinine ≤ 2.5 mg/dL x ULN.
Exclusion Criteria:
-
White blood cell count > 25 x 10e9/L or > 10% peripheral blood blasts;
-
Other invasive malignancies within the last 3 years, except non- melanoma skin cancer and localized cured prostate and cervical cancer;
-
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months;
-
Presence of active serious infection;
-
Any serious, unstable medical or psychiatric condition that would prevent, (as judged by the Investigator) the participant from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study;
-
Known history of human immunodeficiency virus (HIV), or known active hepatitis A, B, or C infection;
-
Organ transplant recipients other than bone marrow transplant;
-
Women who are pregnant or lactating.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Mayo Clinic Cancer Center | Phoenix | Arizona | United States | 85054 |
2 | Stanford Cancer Institute | Palo Alto | California | United States | 94304 |
3 | Emory Hospital | Atlanta | Georgia | United States | 30322 |
4 | University of Maryland Medical Center | Baltimore | Maryland | United States | 21201 |
5 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
6 | University of Michigan | Ann Arbor | Michigan | United States | 48109-2800 |
7 | Mount Sinai Medical Center | New York | New York | United States | 10029 |
8 | Weill Cornell Medical Center | New York | New York | United States | 10065 |
9 | Wake Forest Baptist Medical Center | Winston-Salem | North Carolina | United States | 27157 |
10 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
11 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
12 | Providence Health Care | Vancouver | British Columbia | Canada | V6Z 2A5 |
13 | The Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5T 2M9 |
14 | Hospital Saint-Louis | Paris | France | 75475 | |
15 | University Medical Center RWTH Aachen | Aachen | Germany | D-52074 | |
16 | Johannes Wesling Academic Medical Center | Minden | Germany | 32429 | |
17 | Hadassah Medical Centre | Jerusalem | Israel | 91120 | |
18 | Meir Medical Centre | Kfar Saba | Israel | 4428164 | |
19 | Fondazione IRCCS Policlinico San Matteo | Pavia | Italy | 27100 | |
20 | Marche Nord Hospital | Pesaro | Italy | 61122 | |
21 | Erasmus Medical Center | Rotterdam | Zuid Holland | Netherlands | 3015 CE |
22 | Radboud University Medical Center | Nijmegen | Netherlands | 6525 GA | |
23 | Guy's and St. Thomas' Hospital | London | United Kingdom |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
More Information
Publications
None provided.- BO42355
- PRM-151G-101
- 2015-001718-80
Study Results
Participant Flow
Recruitment Details | A total of 125 participants were enrolled at sites in 8 different countries. |
---|---|
Pre-assignment Detail | 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 |
---|---|---|---|---|---|---|---|---|---|---|
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 | 5 | 5 | 4 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 3 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Main Phase Stage 1 | ||||||||||
STARTED | 0 | 0 | 0 | 0 | 33 | 32 | 32 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 0 | 0 | 20 | 16 | 15 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 13 | 16 | 17 | 0 | 0 | 0 |
Period Title: Main Phase Stage 1 | ||||||||||
STARTED | 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 |
Baseline Characteristics
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 |
---|---|---|---|---|---|---|---|---|
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 Participants | 8 | 7 | 6 | 6 | 33 | 32 | 32 | 124 |
Age (Years) [Mean (Standard Deviation) ] | ||||||||
Mean (Standard Deviation) [Years] |
64.3
(11.4)
|
70.7
(6.3)
|
66.0
(7.3)
|
66.2
(8.6)
|
66.7
(8.7)
|
|||
Age (Years) [Mean (Standard Deviation) ] | ||||||||
Mean (Standard Deviation) [Years] |
70.6
(7.1)
|
70.2
(6.5)
|
69.4
(8.9)
|
70.1
(7.5)
|
||||
Sex: Female, Male (Count of Participants) | ||||||||
Female |
5
62.5%
|
2
28.6%
|
3
50%
|
5
83.3%
|
15
45.5%
|
|||
Male |
3
37.5%
|
5
71.4%
|
3
50%
|
1
16.7%
|
12
36.4%
|
|||
Sex: Female, Male (Count of Participants) | ||||||||
Female |
16
200%
|
8
114.3%
|
11
183.3%
|
35
583.3%
|
||||
Male |
17
212.5%
|
24
342.9%
|
21
350%
|
62
1033.3%
|
||||
Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
Hispanic or Latino |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
3%
|
|||
Not Hispanic or Latino |
8
100%
|
7
100%
|
4
66.7%
|
6
100%
|
25
75.8%
|
|||
Unknown or Not Reported |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
3%
|
|||
Race (NIH/OMB) (Count of Participants) | ||||||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
3%
|
|||
Asian |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
3%
|
|||
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|||
Black or African American |
1
12.5%
|
0
0%
|
1
16.7%
|
0
0%
|
2
6.1%
|
|||
White |
7
87.5%
|
7
100%
|
3
50%
|
6
100%
|
23
69.7%
|
|||
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|||
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|||
Race (NIH/OMB) (Count of Participants) | ||||||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
||||
Asian |
0
0%
|
1
14.3%
|
2
33.3%
|
3
50%
|
||||
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
||||
Black or African American |
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
||||
White |
33
412.5%
|
29
414.3%
|
29
483.3%
|
91
1516.7%
|
||||
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
||||
Unknown or Not Reported |
0
0%
|
1
14.3%
|
1
16.7%
|
2
33.3%
|
Outcome Measures
Title | Stage 1 Main Phase: Overall Response Rate (ORR) |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
Number (90% Confidence Interval) [Percentage of Participants] |
37.5
468.8%
|
14.3
204.3%
|
33.3
555%
|
50.0
833.3%
|
Title | Stage 2 Main Phase: Bone Marrow Response Rate (BMRR) |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Number (95% Confidence Interval) [Percentage of Participants] |
30.3
378.8%
|
31.3
447.1%
|
25.0
416.7%
|
Title | Stage 1 Main + Open-Label Extension (OLE): ORR |
---|---|
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. |
Outcome Measure Data
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. |
---|---|---|---|---|
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). |
Measure Participants | 8 | 7 | 6 | 6 |
Number (90% Confidence Interval) [Percentage of Participants] |
50.0
625%
|
71.4
1020%
|
50.0
833.3%
|
66.7
1111.7%
|
Title | Stage 2 Main + Open-Label Extension (OLE): BMRR |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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). |
Measure Participants | 33 | 32 | 32 |
Number (95% Confidence Interval) [Percentage of Participants] |
30.3
378.8%
|
34.4
491.4%
|
25.0
416.7%
|
Title | Stage 1 Main Phase: BMRR |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
Number (95% Confidence Interval) [Percentage of Participants] |
37.5
468.8%
|
14.3
204.3%
|
16.7
278.3%
|
50.0
833.3%
|
Title | Stage 1 Main Phase: Modified Myeloproliferative Neoplasms Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) Changes |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
Baseline |
23.1
(19.1)
|
16.9
(7.2)
|
26.8
(17.1)
|
15.3
(10.4)
|
Cycle(C)2 Day(D)1 |
-5.3
(12.6)
|
5.7
(11.8)
|
0.5
(8.8)
|
-2.0
(5.0)
|
C3D1 |
-9.1
(10.9)
|
1.9
(5.3)
|
-2.7
(14.8)
|
4.2
(8.0)
|
C4D1 |
-8.7
(10.7)
|
1.0
(8.0)
|
-7.5
(6.0)
|
5.7
(20.9)
|
C5D1 |
-13.2
(13.2)
|
2.6
(6.9)
|
-6.7
(10.6)
|
1.5
(13.6)
|
C6D1 |
-12.2
(9.5)
|
-0.8
(8.3)
|
-5.4
(6.2)
|
4.3
(11.5)
|
C6D29 |
-15.0
(13.7)
|
-2.2
(5.3)
|
-5.3
(4.6)
|
2.3
(8.8)
|
Title | Stage 2 Main Phase: BMRR |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Number (95% Confidence Interval) [Percentage of Participants] |
30.3
378.8%
|
31.3
447.1%
|
25.0
416.7%
|
Title | Stage 2 Main Phase: BMRR - Reduction of Bone Marrow Fibrosis by Visit |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Cycle(C) 4 Day(D) 1 |
10.7
133.8%
|
24.0
342.9%
|
19.2
320%
|
C7D1 |
23.8
297.5%
|
11.8
168.6%
|
10.5
175%
|
C9D29/C10D1 |
30.0
375%
|
21.4
305.7%
|
13.3
221.7%
|
Title | Stage 2 Main Phase: Duration of Bone Marrow Improvement |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Median (95% Confidence Interval) [Weeks] |
NA
|
12.0
|
12.1
|
Title | Stage 2 Main Phase: Hemoglobin Improvement |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Number [Percentage of Participants] |
15.2
190%
|
15.6
222.9%
|
6.3
105%
|
Title | Stage 2 Main Phase: Platelet Improvement |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Number [Percentage of Participants] |
27.3
341.3%
|
34.4
491.4%
|
37.5
625%
|
Title | Stage 2 Main Phase: Symptom Improvement |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
Cycle(C) 2 Day(D) 1 |
5
62.5%
|
2
28.6%
|
1
16.7%
|
C3D1 |
6
75%
|
3
42.9%
|
2
33.3%
|
C4D1 |
3
37.5%
|
4
57.1%
|
2
33.3%
|
C5D1 |
5
62.5%
|
2
28.6%
|
1
16.7%
|
C6D1 |
8
100%
|
3
42.9%
|
3
50%
|
C7D1 |
8
100%
|
5
71.4%
|
0
0%
|
C8D1 |
5
62.5%
|
3
42.9%
|
0
0%
|
C9D1 |
5
62.5%
|
3
42.9%
|
1
16.7%
|
C9D29/C10D1 |
5
62.5%
|
2
28.6%
|
0
0%
|
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 |
---|---|
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. |
Outcome Measure Data
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 |
---|---|---|---|
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. |
Measure Participants | 33 | 32 | 32 |
CR |
0
0%
|
0
0%
|
0
0%
|
PR |
0
0%
|
0
0%
|
0
0%
|
CI |
8
100%
|
6
85.7%
|
2
33.3%
|
SD |
20
250%
|
21
300%
|
26
433.3%
|
PD |
3
37.5%
|
3
42.9%
|
4
66.7%
|
Not evaluable |
2
25%
|
2
28.6%
|
0
0%
|
Title | Stage 1 Main Phase: Maximum Drug Concentration (Cmax) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
133
(48.4)
|
113
(28.1)
|
164
(23.9)
|
112
(90.4)
|
C1D15 |
127
(31.9)
|
126
(27.5)
|
||
C2D1 |
107
(26.9)
|
110
(20.9)
|
149
(29.1)
|
130
(80.2)
|
C6D1 |
142
(70.0)
|
111
(28.0)
|
136
(34.1)
|
142
(27.4)
|
Title | Stage 1 Main Phase: Time to Maximum Concentration (Tmax) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
1.12
|
1.10
|
1.14
|
1.13
|
C1D15 |
1.13
|
1.65
|
||
C2D1 |
1.10
|
1.08
|
1.05
|
1.44
|
C6D1 |
2.00
|
1.07
|
1.17
|
1.01
|
Title | Stage 1 Main Phase: Area Under the Curve up to the Last Measurable Concentration (AUC0-last) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
1810
(72.0)
|
1690
(26.1)
|
2590
(28.7)
|
1500
(158.3)
|
C1D15 |
1460
(142.0)
|
2590
(187.6)
|
||
C2D1 |
127.3
(904)
|
504
(84.7)
|
2990
(92.0)
|
663
(79.5)
|
C6D1 |
698
(63.0)
|
570
(44.8)
|
764
(28.9)
|
703
(33.8)
|
Title | Stage 1 Main Phase: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
2830
(12.9)
|
2050
(29.5)
|
2970
(34.9)
|
3130
(8.6)
|
C1D15 |
3450
(2.8)
|
6060
(23.2)
|
||
C2D1 |
2170
(170.9)
|
4230
(34.8)
|
||
C6D1 |
819
(NA)
|
Title | Stage 1 Main Phase: Terminal Elimination Half-Life (T1/2) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
14.7
(19.2)
|
17.2
(23.7)
|
16.8
(17.7)
|
18.4
(7.9)
|
C1D15 |
31.2
(45.0)
|
40.4
(12.6)
|
||
C2D1 |
18.0
(220.6)
|
30.0
(48.6)
|
||
C6D1 |
1.95
(NA)
|
Title | Stage 1 Main Phase: Clearance (CL) |
---|---|
Description | |
Time Frame | Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
0.258
(9.0)
|
0.362
(31.5)
|
0.269
(32.9)
|
0.233
(33.3)
|
C1D15 |
0.233
(24.9)
|
0.147
(35.0)
|
||
C2D1 |
0.382
(229.9)
|
0.189
(55.5)
|
||
C6D1 |
1.42
(NA)
|
Title | Stage 1 Main Phase: Volume of Distribution (Vd) |
---|---|
Description | |
Time Frame | Pre-dose on Cycles(C) 1, 2 and 6, Day(D) 1 and C1 D15. Each cycle is 28 days |
Outcome Measure Data
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 |
---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 |
C1D1 |
5.47
(10.9)
|
9.00
(28.8)
|
6.52
(26.4)
|
6.17
(38.9)
|
C1D15 |
10.5
(62.4)
|
8.57
(47.6)
|
||
C2D1 |
9.93
(63.0)
|
8.18
(24.5)
|
||
C6D1 |
4.01
(NA)
|
Title | Percentage of Participants With Adverse Events (AEs) and Infusion Related Reactions (IRRs) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|---|---|---|---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 | 33 | 32 | 32 | 13 | 5 | 48 |
AEs |
100
1250%
|
85.7
1224.3%
|
100
1666.7%
|
100
1666.7%
|
100
303%
|
100
312.5%
|
100
312.5%
|
92.3
74.4%
|
100
NaN
|
89.6
NaN
|
IRRs |
0
0%
|
0
0%
|
0
0%
|
16.7
278.3%
|
3.0
9.1%
|
3.1
9.7%
|
6.3
19.7%
|
7.7
6.2%
|
20.0
NaN
|
2.1
NaN
|
Title | Percentage of Participants With Serious Adverse Events (SAEs) and AEs Leading to Study Drug Discontinuation |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
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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 |
---|---|---|---|---|---|---|---|---|---|---|
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. |
Measure Participants | 8 | 7 | 6 | 6 | 33 | 32 | 32 | 13 | 5 | 48 |
SAEs |
25.0
312.5%
|
0
0%
|
0
0%
|
0
0%
|
15.2
46.1%
|
15.6
48.8%
|
28.1
87.8%
|
7.7
6.2%
|
0
NaN
|
22.9
NaN
|
AEs |
25.0
312.5%
|
0
0%
|
0
0%
|
0
0%
|
21.2
64.2%
|
34.4
107.5%
|
37.5
117.2%
|
30.8
24.8%
|
0
NaN
|
27.1
NaN
|
Adverse Events
Time Frame | Baseline up until 6.75 years | |||||||||||||||||||
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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 | ||||||||||
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 (%) | # 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%) | 0/7 (0%) | 1/6 (16.7%) | 0/6 (0%) | 7/33 (21.2%) | 6/32 (18.8%) | 9/32 (28.1%) | 0/13 (0%) | 0/5 (0%) | 7/48 (14.6%) | ||||||||||
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%) | 1/7 (14.3%) | 2/6 (33.3%) | 0/6 (0%) | 11/33 (33.3%) | 14/32 (43.8%) | 14/32 (43.8%) | 5/13 (38.5%) | 2/5 (40%) | 22/48 (45.8%) | ||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||
Anaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Bone marrow failure | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Extramedullary haemopoiesis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Leukocytosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pancytopenia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Thrombocytopenia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Cardiac disorders | ||||||||||||||||||||
Acute coronary syndrome | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Acute myocardial infarction | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Aortic valve stenosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Cardiac failure | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 3 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Cardiopulmonary failure | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Coronary artery disease | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pericardial effusion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Cardiac arrest | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||
Abdominal pain | 0/8 (0%) | 0 | 1/7 (14.3%) | 3 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Femoral hernia, obstructive | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Intestinal ischaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Melaena | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Oesophageal varices haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 2 |
Rectal haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Varices oesophageal | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Intestinal obstruction | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Mouth haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Upper gastrointestinal haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 2 | 0/48 (0%) | 0 |
General disorders | ||||||||||||||||||||
Asthenia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Chest pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Death | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Disease progression | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Inflammation | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Peripheral swelling | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Unevaluable event | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 2 |
Organ failure | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||
Cholecystitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Cholecystitis acute | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Cholelithiasis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Portal hypertension | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Immune system disorders | ||||||||||||||||||||
Anaphylactic reaction | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||
Infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 1/48 (2.1%) | 1 |
Pneumonia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 2/33 (6.1%) | 3 | 1/32 (3.1%) | 1 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 1/5 (20%) | 2 | 3/48 (6.3%) | 3 |
Abscess limb | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Cellulitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Endocarditis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Influenza | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Intervertebral discitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Osteomyelitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Pneumonia fungal | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pseudomonal sepsis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Sepsis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Septic shock | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Upper respiratory tract infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Urinary tract infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Urosepsis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 3 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Enterocolitis infectious | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Gastroenteritis | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pneumonia viral | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Respiratory syncytial virus infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sialoadenitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Wound infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||
Fall | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Infusion related reaction | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Osteoradionecrosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Procedural haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Subdural haematoma | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Multiple fractures | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Post procedural haematoma | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Rib fracture | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Investigations | ||||||||||||||||||||
Eastern Cooperative Oncology Group performance status worsened | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Hepatic enzyme increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||
Cachexia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hyperkalaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hyperuricaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
Back pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Chondrocalcinosis pyrophosphate | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Haemarthrosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Haematoma muscle | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Joint effusion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
Acute myeloid leukaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Malignant neoplasm progression | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Myelofibrosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Primary myelofibrosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Transformation to acute myeloid leukaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hepatic cancer | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Metastatic squamous cell carcinoma | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Squamous cell carcinoma | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 2 | 0/48 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||
Cerebral haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hepatic encephalopathy | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Subarachnoid haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Syncope | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Metabolic encephalopathy | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Renal and urinary disorders | ||||||||||||||||||||
Acute kidney injury | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 2 |
Nephrolithiasis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Renal failure | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Urinary bladder haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 3 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Urinary bladder rupture | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
Chronic obstructive pulmonary disease | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Epistaxis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Pleural effusion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||
Eczema | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Skin ulcer | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Surgical and medical procedures | ||||||||||||||||||||
Aortic valve replacement | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Vascular disorders | ||||||||||||||||||||
Dry gangrene | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Haematoma | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Other (Not Including 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 | 8/8 (100%) | 6/7 (85.7%) | 6/6 (100%) | 6/6 (100%) | 32/33 (97%) | 30/32 (93.8%) | 31/32 (96.9%) | 12/13 (92.3%) | 5/5 (100%) | 32/48 (66.7%) | ||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||
Anaemia | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 5/33 (15.2%) | 11 | 6/32 (18.8%) | 8 | 3/32 (9.4%) | 6 | 1/13 (7.7%) | 2 | 1/5 (20%) | 1 | 6/48 (12.5%) | 12 |
Leukocytosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Splenomegaly | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 3 | 2/32 (6.3%) | 3 | 3/13 (23.1%) | 3 | 0/5 (0%) | 0 | 7/48 (14.6%) | 7 |
Thrombocytopenia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 5/33 (15.2%) | 6 | 4/32 (12.5%) | 5 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 3 |
Leukopenia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Neutropenia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Increased tendency to bruise | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Cardiac disorders | ||||||||||||||||||||
Tachycardia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Palpitations | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Supraventricular extrasystoles | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Endocrine disorders | ||||||||||||||||||||
Hypothyroidism | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Eye disorders | ||||||||||||||||||||
Dry eye | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Vision blurred | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||
Abdominal distension | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 1/48 (2.1%) | 1 |
Abdominal pain | 1/8 (12.5%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 5/33 (15.2%) | 7 | 6/32 (18.8%) | 8 | 4/32 (12.5%) | 5 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Abdominal pain upper | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 2 | 3/13 (23.1%) | 4 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Diarrhoea | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 8/33 (24.2%) | 8 | 5/32 (15.6%) | 5 | 3/32 (9.4%) | 3 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 7/48 (14.6%) | 7 |
Nausea | 2/8 (25%) | 2 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 5/32 (15.6%) | 5 | 4/13 (30.8%) | 5 | 2/5 (40%) | 3 | 3/48 (6.3%) | 5 |
Stomatitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 4 |
Vomiting | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 3 | 5/32 (15.6%) | 9 | 2/13 (15.4%) | 2 | 2/5 (40%) | 2 | 0/48 (0%) | 0 |
Constipation | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/33 (12.1%) | 5 | 4/32 (12.5%) | 4 | 4/32 (12.5%) | 6 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Gingival bleeding | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 3 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Abdominal discomfort | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Abdominal pain lower | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Abdominal tenderness | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Anal incontinence | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Aphthous ulcer | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Flatulence | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Gastrooesophageal reflux disease | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Gingival pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Oral disorder | 1/8 (12.5%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Oral pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Retching | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
General disorders | ||||||||||||||||||||
Asthenia | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/33 (3%) | 1 | 4/32 (12.5%) | 4 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Chest pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Chills | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 5 | 0/32 (0%) | 0 | 1/13 (7.7%) | 2 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Fatigue | 3/8 (37.5%) | 3 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 3 | 1/6 (16.7%) | 1 | 8/33 (24.2%) | 9 | 8/32 (25%) | 10 | 11/32 (34.4%) | 12 | 2/13 (15.4%) | 2 | 0/5 (0%) | 0 | 5/48 (10.4%) | 5 |
Oedema peripheral | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 6/33 (18.2%) | 8 | 3/32 (9.4%) | 4 | 9/32 (28.1%) | 10 | 2/13 (15.4%) | 2 | 0/5 (0%) | 0 | 4/48 (8.3%) | 5 |
Peripheral swelling | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 2/33 (6.1%) | 3 | 1/32 (3.1%) | 1 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pyrexia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 3/6 (50%) | 3 | 4/33 (12.1%) | 4 | 7/32 (21.9%) | 8 | 3/32 (9.4%) | 3 | 0/13 (0%) | 0 | 1/5 (20%) | 2 | 2/48 (4.2%) | 3 |
Chest discomfort | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Gait disturbance | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Early satiety | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Extravasation | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Ill-defined disorder | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Injection site haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Swelling | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Vessel puncture site bruise | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 5 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||
Hepatomegaly | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hepatosplenomegaly | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hyperbilirubinaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||
Bronchitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 5 | 0/32 (0%) | 0 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 2/5 (40%) | 2 | 0/48 (0%) | 0 |
Nasopharyngitis | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 2/32 (6.3%) | 3 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 3/48 (6.3%) | 3 |
Oral herpes | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pneumonia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 4 | 1/32 (3.1%) | 1 | 3/32 (9.4%) | 3 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Sinusitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 3 | 0/5 (0%) | 0 | 1/48 (2.1%) | 2 |
Skin infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Upper respiratory tract infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 2/6 (33.3%) | 2 | 2/33 (6.1%) | 2 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 3/13 (23.1%) | 4 | 0/5 (0%) | 0 | 2/48 (4.2%) | 5 |
Urinary tract infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 2/33 (6.1%) | 4 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 2/13 (15.4%) | 3 | 0/5 (0%) | 0 | 4/48 (8.3%) | 4 |
Cellulitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 1/32 (3.1%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 4/48 (8.3%) | 5 |
Folliculitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Diarrhoea infectious | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Gastroenteritis viral | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Laryngitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Localised infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Lyme disease | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Respiratory syncytial virus infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Rhinitis | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sialoadenitis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Subcutaneous abscess | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Tooth infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Urosepsis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Viral upper respiratory tract infection | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||
Contusion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 1/5 (20%) | 3 | 5/48 (10.4%) | 5 |
Eye contusion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Fall | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 3/32 (9.4%) | 7 | 2/32 (6.3%) | 3 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 6 |
Procedural pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 2/32 (6.3%) | 3 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Ankle fracture | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Arthropod bite | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Foot fracture | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Infusion related reaction | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Post-traumatic pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Road traffic accident | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 3 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Transfusion reaction | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Wound | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Wrist fracture | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Investigations | ||||||||||||||||||||
Alanine aminotransferase increased | 3/8 (37.5%) | 3 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 4/32 (12.5%) | 7 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 2/5 (40%) | 2 | 0/48 (0%) | 0 |
Aspartate aminotransferase increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 5/32 (15.6%) | 9 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 2/5 (40%) | 2 | 0/48 (0%) | 0 |
Blood bilirubin increased | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Weight increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Blood alkaline phosphatase increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 6 | 2/32 (6.3%) | 4 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Blood sodium decreased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Neutrophil count decreased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 3 | 3/32 (9.4%) | 4 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Platelet count decreased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/33 (12.1%) | 8 | 3/32 (9.4%) | 3 | 1/32 (3.1%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Weight decreased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 6/33 (18.2%) | 7 | 8/32 (25%) | 8 | 8/32 (25%) | 11 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 5/48 (10.4%) | 6 |
White blood cell count decreased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 5 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Blood creatine phosphokinase increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 2/5 (40%) | 3 | 0/48 (0%) | 0 |
Blood creatinine increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Blood urea increased | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Blood uric acid increased | 2/8 (25%) | 2 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||
Decreased appetite | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/33 (12.1%) | 5 | 4/32 (12.5%) | 5 | 4/32 (12.5%) | 6 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Gout | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Hyperglycaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 4 | 3/32 (9.4%) | 5 | 1/32 (3.1%) | 2 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 2/48 (4.2%) | 3 |
Hyperuricaemia | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 4/32 (12.5%) | 5 | 4/32 (12.5%) | 4 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hypocalcaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Hypokalaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 1/48 (2.1%) | 2 |
Cachexia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hyperphosphataemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hypomagnesaemia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 3 | 0/48 (0%) | 0 |
Iron deficiency | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Iron overload | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Type 2 diabetes mellitus | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||
Arthralgia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 3/33 (9.1%) | 3 | 5/32 (15.6%) | 5 | 2/32 (6.3%) | 2 | 2/13 (15.4%) | 2 | 4/5 (80%) | 4 | 3/48 (6.3%) | 3 |
Back pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 3/32 (9.4%) | 3 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 1/5 (20%) | 1 | 1/48 (2.1%) | 1 |
Bone pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 3 | 3/32 (9.4%) | 3 | 2/32 (6.3%) | 2 | 1/13 (7.7%) | 1 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Muscle spasms | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 3 | 2/32 (6.3%) | 3 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 3/48 (6.3%) | 3 |
Muscular weakness | 2/8 (25%) | 2 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 2 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Myalgia | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 3 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 2 |
Pain in extremity | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 2/33 (6.1%) | 3 | 5/32 (15.6%) | 5 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Musculoskeletal pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 3/32 (9.4%) | 3 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 2/48 (4.2%) | 2 |
Groin pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Joint lock | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Joint swelling | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Musculoskeletal chest pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Musculoskeletal stiffness | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Neck pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||
Squamous cell carcinoma | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 2/33 (6.1%) | 2 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 3/5 (60%) | 3 | 0/48 (0%) | 0 |
Lipoma | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Neoplasm | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||
Dizziness | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 6/33 (18.2%) | 9 | 3/32 (9.4%) | 3 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 2/48 (4.2%) | 2 |
Headache | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 4/33 (12.1%) | 5 | 7/32 (21.9%) | 8 | 3/32 (9.4%) | 3 | 2/13 (15.4%) | 3 | 2/5 (40%) | 4 | 3/48 (6.3%) | 3 |
Hypoaesthesia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 2/33 (6.1%) | 2 | 1/32 (3.1%) | 1 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Neuropathy peripheral | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 3/33 (9.1%) | 3 | 1/32 (3.1%) | 1 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Nerve compression | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sciatic nerve neuropathy | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sciatica | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||||||
Depression | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 4/32 (12.5%) | 4 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Insomnia | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 1/6 (16.7%) | 1 | 1/33 (3%) | 1 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Delirium | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 3 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sleep disorder | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Renal and urinary disorders | ||||||||||||||||||||
Dysuria | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 2/32 (6.3%) | 2 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Haematuria | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Nocturia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Reproductive system and breast disorders | ||||||||||||||||||||
Vaginal haemorrhage | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||
Cough | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 2/6 (33.3%) | 2 | 1/6 (16.7%) | 1 | 10/33 (30.3%) | 12 | 7/32 (21.9%) | 8 | 5/32 (15.6%) | 5 | 2/13 (15.4%) | 3 | 3/5 (60%) | 4 | 4/48 (8.3%) | 4 |
Dyspnoea | 0/8 (0%) | 0 | 2/7 (28.6%) | 2 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 4/33 (12.1%) | 7 | 8/32 (25%) | 10 | 7/32 (21.9%) | 8 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 4/48 (8.3%) | 4 |
Dyspnoea exertional | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 3/33 (9.1%) | 3 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Epistaxis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 2/6 (33.3%) | 3 | 1/6 (16.7%) | 1 | 5/33 (15.2%) | 7 | 4/32 (12.5%) | 4 | 4/32 (12.5%) | 11 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 7/48 (14.6%) | 16 |
Oropharyngeal pain | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 4/32 (12.5%) | 4 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 1/48 (2.1%) | 1 |
Pleural effusion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Dysphonia | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hypoxia | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Nasal dryness | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Paranasal sinus discomfort | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Pneumothorax | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Rhinitis allergic | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sleep apnoea syndrome | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Sneezing | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Upper-airway cough syndrome | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||
Ecchymosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Night sweats | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 4/32 (12.5%) | 7 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 1/48 (2.1%) | 1 |
Pruritus | 0/8 (0%) | 0 | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 4/32 (12.5%) | 6 | 3/32 (9.4%) | 3 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Urticaria | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Erythema | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Hyperhidrosis | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hyperkeratosis | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Lichen planus | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Petechiae | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 2 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Rash | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Rash erythematous | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Rash pruritic | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Skin induration | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Skin lesion | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 1/6 (16.7%) | 1 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 1/32 (3.1%) | 1 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Social circumstances | ||||||||||||||||||||
Blood product transfusion dependent | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Vascular disorders | ||||||||||||||||||||
Hypotension | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 1/33 (3%) | 1 | 2/32 (6.3%) | 2 | 1/32 (3.1%) | 1 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 3/48 (6.3%) | 3 |
Haematoma | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 1/13 (7.7%) | 1 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hot flush | 1/8 (12.5%) | 1 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 0/5 (0%) | 0 | 0/48 (0%) | 0 |
Hypertension | 0/8 (0%) | 0 | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/33 (0%) | 0 | 0/32 (0%) | 0 | 0/32 (0%) | 0 | 0/13 (0%) | 0 | 1/5 (20%) | 1 | 0/48 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title | Medical Communications |
---|---|
Organization | Hoffmann-La Roche |
Phone | 800-821-8590 |
genentech@druginfo.com |
- BO42355
- PRM-151G-101
- 2015-001718-80