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Efficacy and Safety of Simtuzumab in Adults With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis

Sponsor
Gilead Sciences (Industry)
Overall Status
Completed
CT.gov ID
NCT01369498
Collaborator
(none)
54
Enrollment
7
Locations
4
Arms
38.8
Actual Duration (Months)
7.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is to evaluate the efficacy and safety of simtuzumab (GS-6624) on bone marrow fibrosis either alone or in combination with ruxolitinib in participants with primary myelofibrosis (PMF) and post polycythemia vera or post essential thrombocythemia myelofibrosis (ET/PV MF).

The study is designed as a two-stage trial. In the stage 1, participants will be randomized into two cohorts to receive either 200 or 700 mg of study drug. In the stage 2, participants on ruxolitinib will be randomized to receive either 200 or 700 mg of study drug.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study to Evaluate the Efficacy and Safety of GS-6624 in Adult Subjects With Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis
Actual Study Start Date :
Jun 30, 2011
Actual Primary Completion Date :
Jun 5, 2014
Actual Study Completion Date :
Sep 24, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Simtuzumab 200 mg

Participants in Stage 1 of study will receive simtuzumab 200 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

Drug: Simtuzumab
Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
Other Names:
  • GS-6624
  • AB0024

    		•
    Experimental: Simtuzumab 700 mg

    Participants in Stage 1 of study will receive simtuzumab 700 mg for up to 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

    Drug: Simtuzumab
    Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
    Other Names:
  • GS-6624
  • AB0024

    		•
    Experimental: Simtuzumab 200 mg+Ruxolitinib

    In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 200 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

    Drug: Simtuzumab
    Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
    Other Names:
  • GS-6624
  • AB0024

    • Drug: Ruxolitinib
    In Stage 2, participants will be on a stable dose of ruxolitinib
    Experimental: Simtuzumab 700 mg+Ruxolitinib

    In Stage 2, participants on stable doses of ruxolitinib will receive simtuzumab 700 mg for at least 24 weeks. Treatment could be continued if there is evidence of clinical benefit as judged by the treating physician.

    Drug: Simtuzumab
    Simtuzumab administered intravenously over approximately 30 minutes every 2 weeks
    Other Names:
  • GS-6624
  • AB0024

    • Drug: Ruxolitinib
    In Stage 2, participants will be on a stable dose of ruxolitinib

    Outcome Measures

    Primary Outcome Measures

    1. Rate of Clinical Response as Defined by the Percentage of Participants With Reduction at Week 24 From Baseline in the Bone Marrow Fibrosis Score [Baseline; Week 24]

      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.

    Secondary Outcome Measures

    1. Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC) [Baseline; Weeks 12, 24 and any time post baseline (enrollment up to 94 weeks)]

      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).

    2. Percentage of Participants With Adverse Events (AEs) [First dose date up to the last dose date (maximum: 94 weeks) plus 28 days]

    3. Change From Baseline in Myelofibrosis Symptoms Assessment Score [Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks)]

      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.

    4. Change From Baseline in Cytokine Levels [Baseline; Week 24]

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

    5. Percentage of Participants With Anti-Simtuzumab Antibody Formation [Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks)]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Must be diagnosed with PMF or post ET/PV MF with intermediate-1, intermediate-2 or high risk disease according to the international working group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is ≥ 10 cm below left costal margin by physical exam.

    • Must have adequate organ function as demonstrated by the following:

    • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5x upper limit of normal (ULN), or ≤ 4x 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 extramedullary hematopoiesis [EMH] related to MF);

    • Serum creatinine ≤ 2.5 mg/dL.

    • In Stage 2, participants must be on ruxolitinib for at least 8 weeks and on a stable dose for at least 4 weeks.

    • Eastern cooperative oncology group (ECOG) performance status (PS) ≤ 2

    • Treatment-related toxicities from prior therapies must have resolved to Grade ≤ 1

    • Women of childbearing potential and men must agree to using one medically approved (ie, mechanical or pharmacological) contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug. Definition of female of child bearing potential and a list of acceptable contraceptive methods for this study applies per protocol.

    Exclusion Criteria:

    • Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) 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.

    • Pregnant or lactating.

    • Known history of human immunodeficiency virus (HIV), hepatitis C, or hepatitis B.

    • History or presence of any form of cancer within the 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis.

    • Participation in an investigational drug or device trial within 2 weeks prior to study Day 1 or within 5 times the half-life of the investigational agent in the other clinical study, if known.

    • Use of any cytotoxic chemotherapeutic agents (eg, hydroxyurea), corticosteroids (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immune modulators (eg, thalidomide) within 2 weeks and interferon use within 4 weeks prior to study Day

    • Symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.

    • History of surgery within 2 weeks prior to enrollment or anticipated surgery during the study period.

    • Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Scottsdale Arizona United States 85259
    2 Stanford University Medical center Stanford California United States 94305
    3 Washington University in St. Louis Saint Louis Missouri United States 63110
    4 Oncology Hematology Care Clinical Trials Cincinnati Ohio United States
    5 Cleveland Clinic Cleveland Ohio United States
    6 Tennessee Oncology Nashville Tennessee United States
    7 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Gilead Sciences

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01369498
    Other Study ID Numbers:
    • AB0024-102
    • NCT01242709
    First Posted:
    Jun 9, 2011
    Last Update Posted:
    Jul 1, 2020
    Last Verified:
    Jun 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Gilead Sciences
    Hematology
    Myelofibrosis
    Thrombocythemia Myelofibrosis
    Bone Marrow Diseases
    Hematologic Diseases
    Blood Diseases
    Leukemia
    Blood Disorders
    Additional relevant MeSH terms:
    Polycythemia Vera
    Primary Myelofibrosis
    Polycythemia
    Thrombocytosis
    Thrombocythemia, Essential

    Study Results

    Participant Flow

    Recruitment Details 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.
    Pre-assignment Detail 62 participants were screened.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description 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. 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. 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. 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.
    Period Title: Overall Study
    STARTED 12 12 15 15
    COMPLETED 0 0 0 0
    NOT COMPLETED 12 12 15 15

    Baseline Characteristics

    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib Total
    Arm/Group Description 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. 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. 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. 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 of all reporting groups
    Overall Participants 12 12 15 15 54
    Age, Customized (Count of Participants)
    > 65 years
    9
    75%
    8
    66.7%
    12
    80%
    9
    60%
    38
    70.4%
    ≤ 65 years
    3
    25%
    4
    33.3%
    3
    20%
    6
    40%
    16
    29.6%
    Sex: Female, Male (Count of Participants)
    Female
    6
    50%
    4
    33.3%
    9
    60%
    4
    26.7%
    23
    42.6%
    Male
    6
    50%
    8
    66.7%
    6
    40%
    11
    73.3%
    31
    57.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    8.3%
    0
    0%
    1
    6.7%
    2
    3.7%
    Not Hispanic or Latino
    12
    100%
    11
    91.7%
    15
    100%
    14
    93.3%
    52
    96.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    12
    100%
    11
    91.7%
    13
    86.7%
    14
    93.3%
    50
    92.6%
    Black or African Heritage
    0
    0%
    1
    8.3%
    0
    0%
    1
    6.7%
    2
    3.7%
    Other
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    1
    1.9%
    Asian
    0
    0%
    0
    0%
    1
    6.7%
    0
    0%
    1
    1.9%
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Bone Marrow Fibrosis Score (Count of Participants)
    MF-0
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    MF-1
    2
    16.7%
    1
    8.3%
    1
    6.7%
    3
    20%
    7
    13%
    MF-2
    4
    33.3%
    2
    16.7%
    6
    40%
    5
    33.3%
    17
    31.5%
    MF-3
    5
    41.7%
    8
    66.7%
    8
    53.3%
    7
    46.7%
    28
    51.9%
    Missing
    0
    0%
    1
    8.3%
    0
    0%
    0
    0%
    1
    1.9%

    Outcome Measures

    1. Primary Outcome
    Title Rate of Clinical Response as Defined by the Percentage of Participants With Reduction at Week 24 From Baseline in the Bone Marrow Fibrosis Score
    Description 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.
    Time Frame Baseline; Week 24

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description 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. 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. 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. 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.
    Measure Participants 11 12 15 15
    Number (90% Confidence Interval) [percentage of participants]
    0
    0%
    16.7
    139.2%
    6.7
    44.7%
    13.3
    88.7%
    2. Secondary Outcome
    Title Rate of Clinical Response as Defined by the Percentage of Participants With Improvement in Hemoglobin, Platelet, or Absolute Neutrophil Count (ANC)
    Description 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).
    Time Frame Baseline; Weeks 12, 24 and any time post baseline (enrollment up to 94 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in Per Protocol Analysis Set with available data were analyzed.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description Participants were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks. 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. 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. 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.
    Measure Participants 10 10 9 10
    Week 12
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Week 24
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Any Time Post-Baseline
    0
    0%
    0
    0%
    11.1
    74%
    0
    0%
    3. Secondary Outcome
    Title Percentage of Participants With Adverse Events (AEs)
    Description
    Time Frame First dose date up to the last dose date (maximum: 94 weeks) plus 28 days

    Outcome Measure Data

    Analysis Population Description
    The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description Participants were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks. 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. 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. 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.
    Measure Participants 12 12 15 15
    Number [percentage of participants]
    100
    833.3%
    100
    833.3%
    100
    666.7%
    100
    666.7%
    4. Secondary Outcome
    Title Change From Baseline in Myelofibrosis Symptoms Assessment Score
    Description 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.
    Time Frame Baseline; Days 43 and 85 of Cycles 1-7 (cycle=12 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in the Per Protocol Analysis Set with available data were analyzed.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description Participants were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks. 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. 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. 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.
    Measure Participants 11 12 13 14
    Baseline
    2.5
    (1.75)
    3.7
    (1.86)
    3.2
    (2.06)
    2.2
    (1.34)
    Best Change from Baseline
    -0.9
    (1.11)
    -1.3
    (1.60)
    -1.1
    (1.25)
    -0.6
    (0.98)
    Change from Baseline at Cycle 1 - Day 43
    -0.2
    (0.58)
    -1.0
    (1.66)
    -0.2
    (0.81)
    0.2
    (1.00)
    Change from Baseline at Cycle 1 - Day 85
    -0.3
    (1.59)
    -0.9
    (1.67)
    0.5
    (1.36)
    0.4
    (0.74)
    Change from Baseline at Cycle 2 - Day 43
    -0.3
    (0.99)
    -1.0
    (1.26)
    -0.7
    (1.30)
    0.4
    (1.43)
    Change from Baseline at Cycle 2 - Day 85
    0.3
    (0.89)
    -0.8
    (1.44)
    -0.5
    (1.42)
    0.7
    (1.61)
    Change from Baseline at Cycle 3 - Day 43
    1.1
    (2.81)
    -1.2
    (2.33)
    -0.5
    (1.16)
    -0.3
    (0.58)
    Change from Baseline at Cycle 3 - Day 85
    0.1
    (1.10)
    0.6
    (1.55)
    -0.5
    (1.22)
    -0.8
    (0.39)
    Change from Baseline at Cycle 4 - Day 43
    0
    (NA)
    -0.4
    (1.35)
    -0.6
    (1.29)
    Change from Baseline at Cycle 4 - Day 85
    1.2
    (NA)
    -0.8
    (1.46)
    -0.2
    (0.68)
    Change from Baseline at Cycle 5 - Day 43
    1.8
    (NA)
    -0.6
    (1.22)
    -0.9
    (0.53)
    Change from Baseline at Cycle 5 - Day 85
    1.0
    (NA)
    -1.2
    (1.24)
    -0.9
    (0.91)
    Change from Baseline at Cycle 6 - Day 43
    1.4
    (NA)
    -0.4
    (0.65)
    -0.5
    (0.32)
    Change from Baseline at Cycle 6 - Day 85
    -1.5
    (0.84)
    -0.9
    (NA)
    Change from Baseline at Cycle 7 - Day 43
    -1.4
    (NA)
    -1.4
    (NA)
    Change from Baseline at Cycle 7 - Day 85
    -1.3
    (NA)
    5. Secondary Outcome
    Title Change From Baseline in Cytokine Levels
    Description Biomarker samples were collected to evaluate the effects of SIM treatment on markers of serum and plasma cytokines.
    Time Frame Baseline; Week 24

    Outcome Measure Data

    Analysis Population Description
    The cytokine analysis was not performed.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description Participants were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks. 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. 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. 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.
    Measure Participants 0 0 0 0
    6. Secondary Outcome
    Title Percentage of Participants With Anti-Simtuzumab Antibody Formation
    Description Blood samples were collected for the presence of anti-SIM antibodies which was determined using a validated electro-chemiluminescent (ECL) assay screening test.
    Time Frame Baseline; Day 85 of Cycles 1 to 5 (cycle=12 weeks)

    Outcome Measure Data

    Analysis Population Description
    Participants in Safety Analysis Set with available data were analyzed.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description Participants were administered SIM 200 mg IV infusion over 30 minutes once every 2 weeks for a total of 6 infusions per 12-week cycle for up to 94 weeks. 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. 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. 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.
    Measure Participants 12 11 15 14
    Baseline : Screened Negative
    75.0
    625%
    63.6
    530%
    73.3
    488.7%
    78.6
    524%
    Baseline : Screened Positive
    25.0
    208.3%
    36.4
    303.3%
    26.7
    178%
    21.4
    142.7%
    Cycle 1 - Day 85 : Screened Negative
    100.0
    833.3%
    90.0
    750%
    57.1
    380.7%
    92.3
    615.3%
    Cycle 1 - Day 85 : Screened Positive
    0
    0%
    10.0
    83.3%
    42.9
    286%
    7.7
    51.3%
    Cycle 2 - Day 85 : Screened Negative
    100.0
    833.3%
    85.7
    714.2%
    69.2
    461.3%
    90.9
    606%
    Cycle 2 - Day 85 : Screened Positive
    0
    0%
    14.3
    119.2%
    30.8
    205.3%
    9.1
    60.7%
    Cycle 3 - Day 85 : Screened Negative
    100.0
    833.3%
    100.0
    833.3%
    100.0
    666.7%
    75.0
    500%
    Cycle 3 - Day 85 : Screened Positive
    0
    0%
    0
    0%
    0
    0%
    25.0
    166.7%
    Cycle 4 - Day 85 : Screened Negative
    100.0
    833.3%
    100.0
    833.3%
    100.0
    666.7%
    Cycle 4 - Day 85 : Screened Positive
    0
    0%
    0
    0%
    0
    0%
    Cycle 5 - Day 85 : Screened Negative
    100.0
    833.3%
    100.0
    833.3%
    Cycle 5 - Day 85 : Screened Positive
    0
    0%
    0
    0%

    Adverse Events

    Time Frame First dose date up to the last dose date (maximum: 94 weeks) plus 28 days
    Adverse Event Reporting Description The Safety Analysis Set included participants who were randomized and received at least 1 dose of study drug.
    Arm/Group Title Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Arm/Group Description 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. 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. 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. 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.
    All Cause Mortality
    Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Serious Adverse Events
    Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 8/12 (66.7%) 1/12 (8.3%) 5/15 (33.3%) 4/15 (26.7%)
    Blood and lymphatic system disorders
    Febrile neutropenia 2/12 (16.7%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Gastrointestinal disorders
    Diarrhoea 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    General disorders
    Disease progression 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Pyrexia 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Hepatobiliary disorders
    Bile duct stone 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Cholecystitis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Infections and infestations
    Abdominal infection 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Cellulitis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Gastroenteritis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Lung infection 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Periorbital infection 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Pneumonia 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Respiratory tract infection 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Sepsis 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Septic shock 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Urosepsis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Investigations
    Troponin increased 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hyperkalaemia 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Hyponatraemia 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Haemarthrosis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Neck pain 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Osteoarthritis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Pain in extremity 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Nervous system disorders
    Cerebral haemorrhage 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Convulsion 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Haemorrhage intracranial 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Headache 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Psychiatric disorders
    Confusional state 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Delirium 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Mental status changes 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Renal and urinary disorders
    Renal failure acute 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Vascular disorders
    Hypertension 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Other (Not Including Serious) Adverse Events
    Stage 1: SIM 200 mg Stage 1: SIM 700 mg Stage 2: SIM 200 mg+Ruxolitinib Stage 2: SIM 700 mg+Ruxolitinib
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 12/12 (100%) 12/12 (100%) 15/15 (100%) 15/15 (100%)
    Blood and lymphatic system disorders
    Anaemia 2/12 (16.7%) 2/12 (16.7%) 5/15 (33.3%) 4/15 (26.7%)
    Febrile neutropenia 2/12 (16.7%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Lymphadenopathy 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Neutropenia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Splenomegaly 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Systemic mastocytosis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Thrombocytopenia 1/12 (8.3%) 4/12 (33.3%) 1/15 (6.7%) 2/15 (13.3%)
    Cardiac disorders
    Acute myocardial infarction 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Atrial fibrillation 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Coronary artery disease 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Left ventricular dysfunction 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Mitral valve incompetence 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Palpitations 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Supraventricular tachycardia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Tachycardia 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Ventricular hypokinesia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Ear and labyrinth disorders
    Otorrhoea 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Tinnitus 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Vertigo 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Endocrine disorders
    Hypothyroidism 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Inappropriate antidiuretic hormone secretion 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Eye disorders
    Conjunctival haemorrhage 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%)
    Diplopia 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Eye discharge 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Eye irritation 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Macular fibrosis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Vision blurred 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Visual acuity reduced 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Visual impairment 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Gastrointestinal disorders
    Abdominal distension 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Abdominal pain 1/12 (8.3%) 3/12 (25%) 4/15 (26.7%) 3/15 (20%)
    Abdominal pain upper 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Abdominal tenderness 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%)
    Anal haemorrhage 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Ascites 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Constipation 3/12 (25%) 2/12 (16.7%) 4/15 (26.7%) 5/15 (33.3%)
    Defaecation urgency 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Dental caries 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Diarrhoea 4/12 (33.3%) 4/12 (33.3%) 6/15 (40%) 7/15 (46.7%)
    Dry mouth 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Dyspepsia 0/12 (0%) 1/12 (8.3%) 4/15 (26.7%) 1/15 (6.7%)
    Dysphagia 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Epigastric discomfort 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Faecal incontinence 0/12 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%)
    Flatulence 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Frequent bowel movements 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Gastritis erosive 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Gastrooesophageal reflux disease 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Gingival bleeding 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Gingival pain 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Glossodynia 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Haematochezia 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Haemorrhoidal haemorrhage 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Hiatus hernia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Mouth ulceration 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Nausea 5/12 (41.7%) 5/12 (41.7%) 5/15 (33.3%) 4/15 (26.7%)
    Oral mucosal blistering 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Oral pain 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Periodontal disease 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Rectal haemorrhage 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Stomatitis 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Vomiting 1/12 (8.3%) 3/12 (25%) 3/15 (20%) 3/15 (20%)
    General disorders
    Asthenia 1/12 (8.3%) 1/12 (8.3%) 4/15 (26.7%) 0/15 (0%)
    Catheter site haematoma 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Catheter site pain 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Chest pain 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Chills 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 4/15 (26.7%)
    Cyst 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Early satiety 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Fatigue 5/12 (41.7%) 3/12 (25%) 5/15 (33.3%) 8/15 (53.3%)
    Feeling abnormal 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Inflammation 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Influenza like illness 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Infusion site pain 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Malaise 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Mass 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Mucosal inflammation 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Non-cardiac chest pain 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Oedema peripheral 3/12 (25%) 2/12 (16.7%) 5/15 (33.3%) 1/15 (6.7%)
    Pain 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Peripheral swelling 0/12 (0%) 2/12 (16.7%) 0/15 (0%) 1/15 (6.7%)
    Pyrexia 4/12 (33.3%) 2/12 (16.7%) 2/15 (13.3%) 2/15 (13.3%)
    Hepatobiliary disorders
    Bile duct stone 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Cholecystitis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Cholecystitis chronic 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hepatomegaly 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%)
    Hyperbilirubinaemia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Immune system disorders
    Seasonal allergy 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Infections and infestations
    Bronchitis 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Cellulitis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Conjunctivitis 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Folliculitis 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Gastroenteritis 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Herpes zoster 0/12 (0%) 0/12 (0%) 0/15 (0%) 2/15 (13.3%)
    Influenza 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Labyrinthitis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Lung infection 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Metapneumovirus infection 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Oral herpes 1/12 (8.3%) 0/12 (0%) 5/15 (33.3%) 0/15 (0%)
    Otitis externa 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Otitis media 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Periorbital cellulitis 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Pneumonia 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Pneumonia cryptococcal 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Respiratory syncytial virus infection 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Respiratory tract infection 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Sinusitis 0/12 (0%) 0/12 (0%) 5/15 (33.3%) 2/15 (13.3%)
    Skin infection 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Staphylococcal skin infection 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Tooth abscess 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Tooth infection 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Upper respiratory tract infection 3/12 (25%) 5/12 (41.7%) 3/15 (20%) 2/15 (13.3%)
    Urinary tract infection 4/12 (33.3%) 0/12 (0%) 4/15 (26.7%) 1/15 (6.7%)
    Vaginal infection 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Arthropod bite 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Contusion 0/12 (0%) 1/12 (8.3%) 2/15 (13.3%) 4/15 (26.7%)
    Fall 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 3/15 (20%)
    Head injury 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Joint injury 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Laceration 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Ligament rupture 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Ligament sprain 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Limb injury 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Mouth injury 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Muscle rupture 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Muscle strain 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 1/15 (6.7%)
    Post procedural haematoma 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Post procedural haemorrhage 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Post procedural oedema 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Procedural pain 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%)
    Skin abrasion 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Spinal compression fracture 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Tooth fracture 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Wound 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Investigations
    Alanine aminotransferase increased 2/12 (16.7%) 2/12 (16.7%) 3/15 (20%) 0/15 (0%)
    Aspartate aminotransferase increased 2/12 (16.7%) 1/12 (8.3%) 3/15 (20%) 0/15 (0%)
    Blood bilirubin increased 1/12 (8.3%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Blood pressure increased 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Electrocardiogram qt prolonged 0/12 (0%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%)
    Hepatic enzyme increased 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Liver function test abnormal 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Platelet count decreased 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Weight increased 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Dehydration 0/12 (0%) 1/12 (8.3%) 2/15 (13.3%) 1/15 (6.7%)
    Fluid overload 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hyperglycaemia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hyperkalaemia 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Hyperphosphataemia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hypocalcaemia 1/12 (8.3%) 2/12 (16.7%) 0/15 (0%) 0/15 (0%)
    Hypoglycaemia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hypokalaemia 2/12 (16.7%) 2/12 (16.7%) 0/15 (0%) 1/15 (6.7%)
    Hypomagnesaemia 3/12 (25%) 3/12 (25%) 0/15 (0%) 0/15 (0%)
    Hyponatraemia 1/12 (8.3%) 1/12 (8.3%) 2/15 (13.3%) 0/15 (0%)
    Iron overload 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 2/15 (13.3%)
    Metabolic acidosis 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 3/12 (25%) 3/12 (25%) 2/15 (13.3%) 4/15 (26.7%)
    Back pain 1/12 (8.3%) 1/12 (8.3%) 2/15 (13.3%) 0/15 (0%)
    Bone pain 1/12 (8.3%) 2/12 (16.7%) 1/15 (6.7%) 2/15 (13.3%)
    Coccydynia 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Groin pain 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Joint stiffness 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Joint swelling 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Muscle spasms 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 4/15 (26.7%)
    Muscular weakness 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Musculoskeletal chest pain 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Musculoskeletal pain 1/12 (8.3%) 1/12 (8.3%) 1/15 (6.7%) 2/15 (13.3%)
    Myalgia 3/12 (25%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Neck pain 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Osteoarthritis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Pain in extremity 1/12 (8.3%) 1/12 (8.3%) 1/15 (6.7%) 3/15 (20%)
    Pain in jaw 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Plantar fasciitis 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Tendonitis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Vertebral lesion 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/12 (8.3%) 1/12 (8.3%) 1/15 (6.7%) 1/15 (6.7%)
    Haemangioma of liver 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Keratoacanthoma 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Squamous cell carcinoma of skin 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Nervous system disorders
    Carpal tunnel syndrome 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Cerebrovascular accident 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Cognitive disorder 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Coordination abnormal 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Disturbance in attention 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Dizziness 6/12 (50%) 3/12 (25%) 2/15 (13.3%) 3/15 (20%)
    Dysgeusia 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 2/15 (13.3%)
    Haemorrhage intracranial 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Headache 4/12 (33.3%) 3/12 (25%) 3/15 (20%) 4/15 (26.7%)
    Hypoaesthesia 0/12 (0%) 1/12 (8.3%) 2/15 (13.3%) 2/15 (13.3%)
    Neuropathy peripheral 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 2/15 (13.3%)
    Paraesthesia 2/12 (16.7%) 2/12 (16.7%) 3/15 (20%) 0/15 (0%)
    Presyncope 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Restless legs syndrome 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Sciatica 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Sinus headache 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Somnolence 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Syncope 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    White matter lesion 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Psychiatric disorders
    Confusional state 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Depression 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Disorientation 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Insomnia 2/12 (16.7%) 0/12 (0%) 1/15 (6.7%) 2/15 (13.3%)
    Mental status changes 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Renal and urinary disorders
    Bladder spasm 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Chromaturia 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Dysuria 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Haematuria 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Nocturia 0/12 (0%) 0/12 (0%) 3/15 (20%) 0/15 (0%)
    Pollakiuria 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Renal impairment 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Urethral disorder 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Urinary retention 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Reproductive system and breast disorders
    Menstruation irregular 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Respiratory, thoracic and mediastinal disorders
    Allergic sinusitis 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Atelectasis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Cough 3/12 (25%) 4/12 (33.3%) 3/15 (20%) 2/15 (13.3%)
    Dysphonia 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Dyspnoea 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 1/15 (6.7%)
    Dyspnoea exertional 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Epistaxis 2/12 (16.7%) 0/12 (0%) 5/15 (33.3%) 4/15 (26.7%)
    Haemoptysis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Hypoxia 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Nasal congestion 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 1/15 (6.7%)
    Nasal discomfort 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Oropharyngeal pain 1/12 (8.3%) 2/12 (16.7%) 3/15 (20%) 2/15 (13.3%)
    Productive cough 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Pulmonary hypertension 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 1/15 (6.7%)
    Rales 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Respiratory tract congestion 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Rhinitis allergic 2/12 (16.7%) 1/12 (8.3%) 2/15 (13.3%) 0/15 (0%)
    Sinus congestion 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Upper-airway cough syndrome 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Skin and subcutaneous tissue disorders
    Acne 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Actinic keratosis 1/12 (8.3%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Blood blister 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Dermal cyst 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Dermatitis acneiform 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Ecchymosis 0/12 (0%) 1/12 (8.3%) 1/15 (6.7%) 0/15 (0%)
    Erythema 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Erythema multiforme 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Granuloma annulare 0/12 (0%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Hyperhidrosis 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 1/15 (6.7%)
    Nail disorder 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Nail ridging 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Night sweats 0/12 (0%) 1/12 (8.3%) 3/15 (20%) 1/15 (6.7%)
    Petechiae 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Pruritus 1/12 (8.3%) 2/12 (16.7%) 4/15 (26.7%) 0/15 (0%)
    Purpura 1/12 (8.3%) 1/12 (8.3%) 0/15 (0%) 0/15 (0%)
    Rash 1/12 (8.3%) 0/12 (0%) 2/15 (13.3%) 0/15 (0%)
    Rash erythematous 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Rash papular 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Rosacea 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Skin abrasion 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Skin lesion 0/12 (0%) 0/12 (0%) 2/15 (13.3%) 1/15 (6.7%)
    Telangiectasia 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Urticaria 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Surgical and medical procedures
    Tooth extraction 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Vascular disorders
    Deep vein thrombosis 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)
    Flushing 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Hot flush 0/12 (0%) 1/12 (8.3%) 2/15 (13.3%) 1/15 (6.7%)
    Hypertension 1/12 (8.3%) 1/12 (8.3%) 2/15 (13.3%) 0/15 (0%)
    Hypotension 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Intra-abdominal haematoma 0/12 (0%) 0/12 (0%) 0/15 (0%) 1/15 (6.7%)
    Temporal arteritis 1/12 (8.3%) 0/12 (0%) 0/15 (0%) 0/15 (0%)
    Varicose vein 0/12 (0%) 0/12 (0%) 1/15 (6.7%) 0/15 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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

    Results Point of Contact

    Name/Title Gilead Clinical Study Information Center
    Organization Gilead Sciences
    Phone 1-833-445-3230 (GILEAD-0)
    Email GileadClinicalTrials@gilead.com
    Responsible Party:
    Gilead Sciences
    ClinicalTrials.gov Identifier:
    NCT01369498
    Other Study ID Numbers:
    • AB0024-102
    • NCT01242709
    First Posted:
    Jun 9, 2011
    Last Update Posted:
    Jul 1, 2020
    Last Verified:
    Jun 1, 2020