Trial Outcomes & Findings for Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis (NCT NCT01369498)

Last Updated: 2020-07-01

Results Overview

Overall response for the study drug is defined by the reduction in bone marrow fibrosis score which is on a scale of 0-3 where 0 indicates the scattered linear reticulin with no fiber intersections representing normal marrow and 3 indicates dense increase in reticulin fibrosis with fiber intersections, often with osteosclerosis. Reduction from baseline of score indicates improvement in clinical condition.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

Baseline; Week 24

Results posted on

2020-07-01

Participant Flow

Participants were enrolled at study sites in the United States. The first participant was screened on 30 June 2011. The last study visit occurred on 24 September 2014.

62 participants were screened.

Participant milestones

Participant milestones
Measure	Stage 1: SIM 200 mg Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Overall Study STARTED	12	12	15	15
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	12	12	15	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Stage 1: SIM 200 mg Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Overall Study Lack of Efficacy	9	9	1	3
Overall Study Adverse Event	1	2	0	1
Overall Study Withdrawal of Consent	0	1	1	1
Overall Study Death	0	0	1	0
Overall Study Investigator's Discretion	1	0	1	3
Overall Study Unknown Reason	1	0	11	6
Overall Study Disease Progression	0	0	0	1

Baseline Characteristics

The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stage 1: SIM 200 mg n=12 Participants Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg n=12 Participants Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.	Total n=54 Participants Total of all reporting groups
Age, Customized Age · > 65 years	9 Participants n=12 Participants	8 Participants n=12 Participants	12 Participants n=15 Participants	9 Participants n=15 Participants	38 Participants n=54 Participants
Age, Customized Age · ≤ 65 years	3 Participants n=12 Participants	4 Participants n=12 Participants	3 Participants n=15 Participants	6 Participants n=15 Participants	16 Participants n=54 Participants
Sex: Female, Male Female	6 Participants n=12 Participants	4 Participants n=12 Participants	9 Participants n=15 Participants	4 Participants n=15 Participants	23 Participants n=54 Participants
Sex: Female, Male Male	6 Participants n=12 Participants	8 Participants n=12 Participants	6 Participants n=15 Participants	11 Participants n=15 Participants	31 Participants n=54 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=12 Participants	1 Participants n=12 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	2 Participants n=54 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=12 Participants	11 Participants n=12 Participants	15 Participants n=15 Participants	14 Participants n=15 Participants	52 Participants n=54 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=54 Participants
Race/Ethnicity, Customized Race · White	12 Participants n=12 Participants	11 Participants n=12 Participants	13 Participants n=15 Participants	14 Participants n=15 Participants	50 Participants n=54 Participants
Race/Ethnicity, Customized Race · Black or African Heritage	0 Participants n=12 Participants	1 Participants n=12 Participants	0 Participants n=15 Participants	1 Participants n=15 Participants	2 Participants n=54 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=12 Participants	0 Participants n=12 Participants	1 Participants n=15 Participants	0 Participants n=15 Participants	1 Participants n=54 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=12 Participants	0 Participants n=12 Participants	1 Participants n=15 Participants	0 Participants n=15 Participants	1 Participants n=54 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=54 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Pacific Islander	0 Participants n=12 Participants	0 Participants n=12 Participants	0 Participants n=15 Participants	0 Participants n=15 Participants	0 Participants n=54 Participants
Bone Marrow Fibrosis Score MF-0	0 Participants n=11 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	0 Participants n=12 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	0 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	0 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	0 Participants n=53 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.
Bone Marrow Fibrosis Score MF-1	2 Participants n=11 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	1 Participants n=12 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	1 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	3 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	7 Participants n=53 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.
Bone Marrow Fibrosis Score MF-2	4 Participants n=11 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	2 Participants n=12 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	6 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	5 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	17 Participants n=53 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.
Bone Marrow Fibrosis Score MF-3	5 Participants n=11 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	8 Participants n=12 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	8 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	7 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	28 Participants n=53 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.
Bone Marrow Fibrosis Score Missing	0 Participants n=11 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	1 Participants n=12 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	0 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	0 Participants n=15 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.	1 Participants n=53 Participants • The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria and had at least 80% adherence with study drug. It is measured on a scale of 0-3 where 0 indicates normal marrow and 3 indicates fibrosis. For additional description, please see outcome measure 1.

PRIMARY outcome

Timeframe: Baseline; Week 24

Population: The Per Protocol Analysis Set included participants who were randomized, received at least 1 dose of study drug, did not violate any major entry criteria, and had at least 80% adherence with study drug.

Outcome measures

Outcome measures
Measure	Stage 1: SIM 200 mg n=11 Participants Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg n=12 Participants Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Rate of Clinical Response as Defined by the Percentage of Participants With Reduction at Week 24 From Baseline in the Bone Marrow Fibrosis Score	0 percentage of participants Interval 0.0 to 23.8	16.7 percentage of participants Interval 3.0 to 43.8	6.7 percentage of participants Interval 0.3 to 27.9	13.3 percentage of participants Interval 2.4 to 36.3

SECONDARY outcome

Timeframe: Baseline; Weeks 12, 24 and any time post baseline (enrollment up to 94 weeks)

Population: Participants in Per Protocol Analysis Set with available data were analyzed.

Overall response for the study drug was defined by the rate of clinical improvement in hemoglobin, platelet or ANC. Clinical improvement in hemoglobin was defined as a ≥ 2 g/dL increase from baseline in hemoglobin level and transfusion independent (absence of red blood cell (RBC) transfusions in prior 8 weeks and applicable only for participants with baseline hemoglobin level of \< 10 g/dL); clinical improvement in platelets was defined as a ≥ 100% increase from baseline in platelet count and an absolute platelet count of ≥ 50 x 10\^9/L (applicable only for participants with baseline platelet count \< 50 x 10\^9/L); clinical improvement in ANC is defined as a ≥ 100% increase from baseline in ANC and an ANC of ≥ 0.5 x 10\^9/L (applicable only for participants with baseline ANC \< 1 x 10\^9/L).

Outcome measures

Outcome measures
Measure	Stage 1: SIM 200 mg n=10 Participants Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg n=10 Participants Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib n=9 Participants Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib n=10 Participants Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC) Week 12	0 percentage of participants Interval 0.0 to 25.9	0 percentage of participants Interval 0.0 to 25.9	0 percentage of participants Interval 0.0 to 28.3	0 percentage of participants Interval 0.0 to 25.9
Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC) Week 24	0 percentage of participants Interval 0.0 to 25.9	0 percentage of participants Interval 0.0 to 25.9	0 percentage of participants Interval 0.0 to 28.3	0 percentage of participants Interval 0.0 to 25.9
Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC) Any Time Post-Baseline	0 percentage of participants Interval 0.0 to 25.9	0 percentage of participants Interval 0.0 to 25.9	11.1 percentage of participants Interval 0.6 to 42.9	0 percentage of participants Interval 0.0 to 25.9

SECONDARY outcome

Timeframe: First dose date up to the last dose date (maximum: 94 weeks) plus 28 days

Population: The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Stage 1: SIM 200 mg n=12 Participants Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg n=12 Participants Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Percentage of Participants With Adverse Events (AEs)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks)

Population: Participants in the Per Protocol Analysis Set with available data were analyzed.

Myelofibrosis symptom assessment was performed using myeloproliferative neoplasm symptoms assessment form (MPN-SAF) which is a 27-item questionnaire to address symptom burden and quality of life. The form consists of 27 questions which are scored on a scale of 0-10 by participants based on how symptoms are affecting them, where 0 indicates less symptoms while 10 indicated more severe symptoms and greater inactivity. The MPN-SAF score was calculated at each visit for each participant as an average of the scales for each question and all answered questions. If the number of questions not answered at 1 visit was \> 10, then the MPN-SAF score for that visit was taken as missing. A negative change from Baseline indicated improvement.

Outcome measures

Outcome measures
Measure	Stage 1: SIM 200 mg n=11 Participants Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg n=12 Participants Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib n=13 Participants Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib n=14 Participants Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Change From Baseline in Myelofibrosis Symptoms Assessment Score Baseline	2.5 score on a scale Standard Deviation 1.75	3.7 score on a scale Standard Deviation 1.86	3.2 score on a scale Standard Deviation 2.06	2.2 score on a scale Standard Deviation 1.34
Change From Baseline in Myelofibrosis Symptoms Assessment Score Best Change from Baseline	-0.9 score on a scale Standard Deviation 1.11	-1.3 score on a scale Standard Deviation 1.60	-1.1 score on a scale Standard Deviation 1.25	-0.6 score on a scale Standard Deviation 0.98
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 1 - Day 43	-0.2 score on a scale Standard Deviation 0.58	-1.0 score on a scale Standard Deviation 1.66	-0.2 score on a scale Standard Deviation 0.81	0.2 score on a scale Standard Deviation 1.00
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 1 - Day 85	-0.3 score on a scale Standard Deviation 1.59	-0.9 score on a scale Standard Deviation 1.67	0.5 score on a scale Standard Deviation 1.36	0.4 score on a scale Standard Deviation 0.74
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 2 - Day 43	-0.3 score on a scale Standard Deviation 0.99	-1.0 score on a scale Standard Deviation 1.26	-0.7 score on a scale Standard Deviation 1.30	0.4 score on a scale Standard Deviation 1.43
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 2 - Day 85	0.3 score on a scale Standard Deviation 0.89	-0.8 score on a scale Standard Deviation 1.44	-0.5 score on a scale Standard Deviation 1.42	0.7 score on a scale Standard Deviation 1.61
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 3 - Day 43	1.1 score on a scale Standard Deviation 2.81	-1.2 score on a scale Standard Deviation 2.33	-0.5 score on a scale Standard Deviation 1.16	-0.3 score on a scale Standard Deviation 0.58
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 3 - Day 85	0.1 score on a scale Standard Deviation 1.10	0.6 score on a scale Standard Deviation 1.55	-0.5 score on a scale Standard Deviation 1.22	-0.8 score on a scale Standard Deviation 0.39
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 4 - Day 43	0 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	—	-0.4 score on a scale Standard Deviation 1.35	-0.6 score on a scale Standard Deviation 1.29
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 4 - Day 85	1.2 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	—	-0.8 score on a scale Standard Deviation 1.46	-0.2 score on a scale Standard Deviation 0.68
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 5 - Day 43	1.8 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	—	-0.6 score on a scale Standard Deviation 1.22	-0.9 score on a scale Standard Deviation 0.53
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 5 - Day 85	1.0 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	—	-1.2 score on a scale Standard Deviation 1.24	-0.9 score on a scale Standard Deviation 0.91
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 6 - Day 43	1.4 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	—	-0.4 score on a scale Standard Deviation 0.65	-0.5 score on a scale Standard Deviation 0.32
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 6 - Day 85	—	—	-1.5 score on a scale Standard Deviation 0.84	-0.9 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 7 - Day 43	—	—	-1.4 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	-1.4 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants
Change From Baseline in Myelofibrosis Symptoms Assessment Score Change from Baseline at Cycle 7 - Day 85	—	—	-1.3 score on a scale Standard Deviation NA Standard deviation was not calculated due to low number of participants	—

SECONDARY outcome

Timeframe: Baseline; Week 24

Population: The cytokine analysis was not performed.

Biomarker samples were collected to evaluate the effects of SIM treatment on markers of serum and plasma cytokines.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks)

Population: Participants in Safety Analysis Set with available data were analyzed.

Blood samples were collected for the presence of anti-SIM antibodies which was determined using a validated electro-chemiluminescent (ECL) assay screening test.

Outcome measures

Outcome measures
Measure	Stage 1: SIM 200 mg n=12 Participants Participants were administered simtuzumab (SIM) 200 mg intravenous (IV) infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks.	Stage 1: SIM 700 mg n=11 Participants Participants were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 40 weeks.	Stage 2: SIM 200 mg+Ruxolitinib n=15 Participants Participants on a stable dose of ruxolitinib were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for up to 91 weeks.	Stage 2: SIM 700 mg+Ruxolitinib n=14 Participants Participants on a stable dose of ruxolitinib were administered SIM 700 mg IV infusion over 30 minutes once every 2 weeks for up to 86 weeks.
Percentage of Participants With Anti-Simtuzumab Antibody Formation Baseline : Screened Negative	75.0 Percentage of participants	63.6 Percentage of participants	73.3 Percentage of participants	78.6 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Baseline : Screened Positive	25.0 Percentage of participants	36.4 Percentage of participants	26.7 Percentage of participants	21.4 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 1 - Day 85 : Screened Negative	100.0 Percentage of participants	90.0 Percentage of participants	57.1 Percentage of participants	92.3 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 1 - Day 85 : Screened Positive	0 Percentage of participants	10.0 Percentage of participants	42.9 Percentage of participants	7.7 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 2 - Day 85 : Screened Negative	100.0 Percentage of participants	85.7 Percentage of participants	69.2 Percentage of participants	90.9 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 2 - Day 85 : Screened Positive	0 Percentage of participants	14.3 Percentage of participants	30.8 Percentage of participants	9.1 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 3 - Day 85 : Screened Negative	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	75.0 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 3 - Day 85 : Screened Positive	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants	25.0 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 4 - Day 85 : Screened Negative	100.0 Percentage of participants	—	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 4 - Day 85 : Screened Positive	0 Percentage of participants	—	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 5 - Day 85 : Screened Negative	—	—	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Anti-Simtuzumab Antibody Formation Cycle 5 - Day 85 : Screened Positive	—	—	0 Percentage of participants	0 Percentage of participants

Adverse Events

Stage 1: SIM 200 mg

Serious events: 8 serious events

Other events: 12 other events

Deaths: 0 deaths

Stage 1: SIM 700 mg

Serious events: 1 serious events

Other events: 12 other events

Deaths: 1 deaths

Stage 2: SIM 200 mg+Ruxolitinib

Serious events: 5 serious events

Other events: 15 other events

Deaths: 1 deaths

Stage 2: SIM 700 mg+Ruxolitinib

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER