Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

Sponsor
Sierra Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02515630
Collaborator
(none)
41
13
1
18.5
3.2
0.2

Study Details

Study Description

Brief Summary

This study will evaluate the transfusion independence response rate in transfusion-dependent adults with myelofibrosis after treatment with momelotinib (MMB).

Study Design

Study Type:
Interventional
Actual Enrollment :
41 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Open-label, Translational Biology Study of Momelotinib in Transfusion-Dependent Subjects With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
Actual Study Start Date :
Jan 29, 2016
Actual Primary Completion Date :
Jul 18, 2017
Actual Study Completion Date :
Aug 15, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Momelotinib

MMB for 24 weeks (± 7 days)

Drug: MMB
Momelotinib (MMB) tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
  • Outcome Measures

    Primary Outcome Measures

    1. Transfusion Independence Response by Week 24 [From baseline to Week 24]

      The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study. A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period.

    Secondary Outcome Measures

    1. Transfusion Response Rate by Week 24 [From baseline to Week 24]

      The percentage of subjects who became transfusion independent for ≥ 8 weeks, defined as no RBC transfusions for at least an 8-week period at any time on study.

    2. Splenic Response Rate at Week 24 [Measured at Week 24]

      The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI at Week 24.

    3. Response Rate in Total Symptom Score (TSS) at Week 24 [Measured at Week 24]

      The percentage of subjects achieving a ≥ 50% reduction from baseline in TSS at Week 24, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) diary. Total symptom score was assessed using the modified MPN-SAF TSS Version 2, an 8-item questionnaire developed to assess symptom burden and quality of life in patients with MPN. The modified MPN-SAF TSS contained 8 questions, 7 of which were summed to generate the score (the included questions related to tiredness, early satiety, abdominal discomfort, night sweats, itching, bone pain, and pain under the ribs on the left side). Each question is scored on a scale of 0-10, where higher numbers indicate more severe symptoms. For this study, the TSS scale ranges from 0 to 70. The questionnaire was completed daily on an electronic diary device.

    4. Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change [At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24]

      Hepcidin daily change (in nM) was calculated as the predose value subtracted from the 6 hours postdose value at each study visit. Daily hepcidin change at the baseline visit was the difference between 2 values obtained 6 hours apart. No momelotinib was administered on that day.

    5. Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin [At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24]

      Median hepcidin at trough was assessed predose at each study visit.

    6. Change in Markers of Iron Metabolism and Anemia - Serum Iron [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in serum iron, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    7. Change in Markers of Iron Metabolism and Anemia - Hemoglobin [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in hemoglobin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    8. Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in total iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    9. Change in Markers of Iron Metabolism and Anemia - Reticulocytes [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in reticulocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    10. Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes% [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in reticulocytes/erythrocytes%, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    11. Change in Markers of Iron Metabolism and Anemia - Erythropoietin [At Weeks 8 and 20]

      Percent change in erythropoietin at Weeks 8 and 20. The baseline erythropoietin value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    12. Change in Markers of Iron Metabolism and Anemia - Erythrocytes [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in erythrocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    13. Change in Markers of Iron Metabolism and Anemia - Hematocrit [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in hematocrit, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    14. Change in Markers of Iron Metabolism and Anemia - Ferritin [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in ferritin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    15. Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in soluble transferrin receptor, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    16. Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in transferrin saturation, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    17. Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in unsaturated iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    18. Change in Markers of Iron Metabolism and Anemia - Platelets [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in platelets, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    19. Change in Markers of Iron Metabolism and Anemia - Leukocytes [At Weeks 2, 4, 8, 12, 16, 20 and 24]

      Percent change from baseline in leukocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    20. Change in Markers of Iron Metabolism and Anemia - Blasts [At Weeks 2 and 4]

      Change from baseline in % blasts at Weeks 2 and 4. The baseline % blasts value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    21. Change in Liver Iron Content [Measured at Week 24]

      Percent change from baseline in liver iron content assessed by MRI. The baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    22. Change in Pharmacodynamics Biomarker - pSTAT3 [On Day 1 and at Weeks 4 and 24]

      Percent change in %pSTAT stimulated CD3+/4+ T cell at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).

    23. Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio [On Day 1 and at Weeks 4 and 24]

      Percent change in %pSTAT/%tSTAT Stimulated CD3+/4+ T cell ratio at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).

    24. Change in Inflammatory Markers - C-Reactive Protein (CRP) [At Weeks 2, 12 and 24]

      Percent change in C-reactive protein at Weeks 2, 12 and 24. The baseline C-reactive protein value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:
    • Diagnosis of PMF or Post PV/ET-MF

    • Requires myelofibrosis therapy, in the opinion of the investigator

    • High risk OR intermediate-2 risk defined by dynamic international prognostic scoring system (DIPSS) OR intermediate-1 risk defined by DIPSS and associated with symptomatic splenomegaly and/or hepatomegaly

    • Transfusion dependent at baseline, defined as ≥ 4 U red blood cell (RBC) transfusion in the 8 weeks prior to first dose of MMB

    • Acceptable organ function as evidenced by the following:

    • Platelet Count ≥ 50 x 10^9/L

    • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN) or AST or ALT ≤ 5 x ULN if liver is involved by disease process as judged by the investigator

    • Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance of ≥ 60 mL/min

    • Direct bilirubin ≤ 2.0 x ULN

    • Life expectancy of > 24 weeks

    • Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

    • Lactating females must agree to discontinue nursing before MMB administration

    • Able to understand and willing to sign the informed consent form

    Key Exclusion Criteria:
    • Prior splenectomy

    • Splenic irradiation within 3 months prior to the first dose of MMB

    • Prior treatment with MMB

    • Known positive status of human immunodeficiency virus (HIV)

    • Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier

    • Use of strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks prior to the first dose of MMB

    • Uncontrolled intercurrent illness per protocol

    • Treatment with a Janus kinase (JAK) inhibitor within 21 days of the planned first dose of MMB

    • Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2

    • Unwilling or unable to undergo a MRI per requirements in the study protocol

    • Unwilling to consent to genomics sampling

    Note: Other protocol defined Inclusion/Exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Arizona United States
    2 Los Angeles California United States
    3 Orange California United States
    4 Jacksonville Florida United States
    5 Baltimore Maryland United States
    6 Ann Arbor Michigan United States
    7 Saint Louis Missouri United States
    8 Bronx New York United States
    9 New York New York United States
    10 Durham North Carolina United States
    11 Cleveland Ohio United States
    12 Houston Texas United States
    13 Toronto Ontario Canada

    Sponsors and Collaborators

    • Sierra Oncology, Inc.

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sierra Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02515630
    Other Study ID Numbers:
    • GS-US-352-1672
    First Posted:
    Aug 5, 2015
    Last Update Posted:
    Jan 20, 2021
    Last Verified:
    Jan 1, 2021

    Study Results

    Participant Flow

    Recruitment Details This study enrolled transfusion-dependent myelofibrosis patients at oncology centers in the United States and Canada. Following completion of the 24-week study period, patients who were benefiting had the option to continue maintenance momelotinib treatment in an open-label extension study (NCT02124746).
    Pre-assignment Detail
    Arm/Group Title Momelotinib (MMB)
    Arm/Group Description Subjects received oral MMB at a starting dose of 200 mg once daily for 24 weeks (± 7 days) on study.
    Period Title: Overall Study
    STARTED 41
    COMPLETED 25
    NOT COMPLETED 16

    Baseline Characteristics

    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 Total of all reporting groups
    Overall Participants 14 27 41
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    65
    (10.0)
    72
    (7.5)
    70
    (9.0)
    Sex: Female, Male (Count of Participants)
    Female
    6
    42.9%
    9
    33.3%
    15
    36.6%
    Male
    8
    57.1%
    18
    66.7%
    26
    63.4%
    Race/Ethnicity, Customized (Count of Participants)
    Black
    1
    7.1%
    2
    7.4%
    3
    7.3%
    White
    11
    78.6%
    25
    92.6%
    36
    87.8%
    Not Permitted
    1
    7.1%
    0
    0%
    1
    2.4%
    Other
    1
    7.1%
    0
    0%
    1
    2.4%
    Spleen Volume (cm^3) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [cm^3]
    2132.2
    (1439.5)
    2018.1
    (1248.5)
    2057.1
    (1299.8)
    Total Symptom Score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    19.00
    (16.14)
    21.73
    (13.97)
    20.73
    (14.65)
    RBC Units Transfused within 8 weeks prior to Enrollment (Units of red blood cell) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Units of red blood cell]
    5
    (1.9)
    7
    (2.2)
    6
    (2.3)
    Hepcidin (nM) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nM]
    22.0
    42.4
    36.6
    Serum iron (ug/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ug/dL]
    96.0
    127.0
    119.0
    Hemoglobin (g/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [g/dL]
    8.5
    7.8
    8.0
    Total iron binding capacity (ug/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ug/dL]
    214.5
    201.0
    205.0
    Reticulocytes (cells*10^6/uL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [cells*10^6/uL]
    0.096
    0.067
    0.071
    Reticulocytes/erythrocytes (%) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [%]
    3.5
    2.2
    2.4
    Erythropoietin (mIU/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mIU/mL]
    238.7
    88.1
    109.8
    Erythrocytes (cells*10^6/uL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [cells*10^6/uL]
    3.0
    2.8
    2.9
    Hematocrit (%) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [%]
    27.5
    24.0
    25.0
    Ferritin (ng/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ng/mL]
    605.9
    1259.4
    1008.9
    Soluble transferrin receptor (mg/L) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/L]
    2.5
    1.3
    1.6
    Transferrin saturation (%) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [%]
    43.0
    56.5
    53.0
    Unsaturated iron binding capacity (ug/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ug/dL]
    113.5
    81.0
    92.0
    Platelets (cells*10^3/uL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [cells*10^3/uL]
    190.5
    134.0
    146.0
    Leukocytes (cells*10^3/uL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [cells*10^3/uL]
    6.4
    8.5
    6.4
    Blasts (%) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [%]
    0
    2.0
    2.0
    Liver Iron Content (mg/g) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/g]
    2.4
    4.2
    3.5
    %pSTAT Stimulated CD3+/4+ T cell (%) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [%]
    85.1
    77.8
    79.8
    %pSTAT %tSTAT Stimulated CD3+/4+ T cell Ratio (ratio) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ratio]
    0.9
    0.8
    0.9
    C-Reactive Protein (mg/dL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [mg/dL]
    0.7
    1.8
    1.2

    Outcome Measures

    1. Primary Outcome
    Title Transfusion Independence Response by Week 24
    Description The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study. A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period.
    Time Frame From baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that 6 subjects discontinued prior to Week 12 and could not be evaluated over the minimum period required for assessment of the endpoint (12 weeks).
    Arm/Group Title Total
    Arm/Group Description All enrolled subjects
    Measure Participants 41
    Number (90% Confidence Interval) [percentage of subjects]
    34.1
    2. Secondary Outcome
    Title Transfusion Response Rate by Week 24
    Description The percentage of subjects who became transfusion independent for ≥ 8 weeks, defined as no RBC transfusions for at least an 8-week period at any time on study.
    Time Frame From baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that 3 subjects discontinued prior to Week 8 and could not be evaluated over the minimum period required for assessment of the endpoint (8 weeks).
    Arm/Group Title Total
    Arm/Group Description All enrolled subjects
    Measure Participants 41
    Number (90% Confidence Interval) [percentage of subjects]
    39.0
    3. Secondary Outcome
    Title Splenic Response Rate at Week 24
    Description The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI at Week 24.
    Time Frame Measured at Week 24

    Outcome Measure Data

    Analysis Population Description
    Assessed in the Safety Analysis Set, which includes all subjects who received ≥ 1 dose of momelotinib. Note that spleen volume at Week 24 was not available for 15 subjects.
    Arm/Group Title Total
    Arm/Group Description All enrolled subjects
    Measure Participants 41
    Number (90% Confidence Interval) [percentage of subjects]
    12.2
    4. Secondary Outcome
    Title Response Rate in Total Symptom Score (TSS) at Week 24
    Description The percentage of subjects achieving a ≥ 50% reduction from baseline in TSS at Week 24, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) diary. Total symptom score was assessed using the modified MPN-SAF TSS Version 2, an 8-item questionnaire developed to assess symptom burden and quality of life in patients with MPN. The modified MPN-SAF TSS contained 8 questions, 7 of which were summed to generate the score (the included questions related to tiredness, early satiety, abdominal discomfort, night sweats, itching, bone pain, and pain under the ribs on the left side). Each question is scored on a scale of 0-10, where higher numbers indicate more severe symptoms. For this study, the TSS scale ranges from 0 to 70. The questionnaire was completed daily on an electronic diary device.
    Time Frame Measured at Week 24

    Outcome Measure Data

    Analysis Population Description
    There were 3 subjects with missing TSS at baseline who were excluded from the analysis. Note that of the 38 subjects evaluated, 17 were missing Week 24 TSS assessments.
    Arm/Group Title Total
    Arm/Group Description All enrolled subjects
    Measure Participants 38
    Number (90% Confidence Interval) [percentage of subjects]
    15.8
    5. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change
    Description Hepcidin daily change (in nM) was calculated as the predose value subtracted from the 6 hours postdose value at each study visit. Daily hepcidin change at the baseline visit was the difference between 2 values obtained 6 hours apart. No momelotinib was administered on that day.
    Time Frame At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Baseline
    -1.7
    0.1
    0.0
    Day 1
    -4.8
    -11.2
    -8.6
    Week 2
    -4.9
    -6.7
    -6.3
    Week 4
    -2.6
    -7.4
    -5.4
    Week 8
    -2.9
    -5.2
    -4.4
    Week 12
    -1.4
    -5.7
    -4.1
    Week 16
    -0.4
    -4.3
    -2.7
    Week 20
    0.0
    -7.8
    -5.3
    Week 24
    -1.0
    -1.8
    -1.4
    6. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin
    Description Median hepcidin at trough was assessed predose at each study visit.
    Time Frame At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Baseline
    22.0
    42.4
    36.6
    Day 1
    19.7
    43.7
    36.5
    Week 2
    25.1
    52.1
    38.4
    Week 4
    19.8
    46.4
    37.6
    Week 8
    16.6
    51.7
    35.5
    Week 12
    21.3
    44.7
    30.4
    Week 16
    16.9
    51.9
    34.5
    Week 20
    13.4
    44.2
    27.5
    Week 24
    15.5
    51.5
    28.4
    7. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Serum Iron
    Description Percent change from baseline in serum iron, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    4.5
    5.9
    5.9
    Week 4
    39.8
    5.7
    13.3
    Week 8
    9.3
    5.4
    6.4
    Week 12
    3.0
    14.3
    12.8
    Week 16
    -15.5
    16.5
    8.9
    Week 20
    -11.1
    9.9
    1.9
    Week 24
    -8.1
    -5.1
    -6.6
    8. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Hemoglobin
    Description Percent change from baseline in hemoglobin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    12.8
    9.2
    9.9
    Week 4
    8.3
    6.3
    6.9
    Week 8
    12.4
    0.4
    5.6
    Week 12
    15.6
    4.5
    7.5
    Week 16
    12.3
    0.6
    10.2
    Week 20
    13.1
    6.9
    7.4
    Week 24
    10.0
    5.8
    7.9
    9. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity
    Description Percent change from baseline in total iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    4.5
    2.0
    2.8
    Week 4
    6.7
    1.5
    2.2
    Week 8
    4.9
    0.6
    2.4
    Week 12
    6.6
    2.4
    6.6
    Week 16
    4.5
    1.5
    3.6
    Week 20
    15.5
    5.5
    10.6
    Week 24
    7.3
    0.5
    5.5
    10. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Reticulocytes
    Description Percent change from baseline in reticulocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    33.6
    -9.6
    2.9
    Week 4
    11.8
    5.5
    7.5
    Week 8
    30.0
    -16.0
    15.6
    Week 12
    15.8
    -9.5
    4.8
    Week 16
    31.2
    8.8
    18.3
    Week 20
    34.0
    7.7
    16.3
    Week 24
    29.9
    -0.6
    24.1
    11. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes%
    Description Percent change from baseline in reticulocytes/erythrocytes%, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    30.0
    -16.3
    -8.0
    Week 4
    8.2
    1.5
    4.1
    Week 8
    12.4
    -11.1
    0.0
    Week 12
    3.6
    0.0
    0.0
    Week 16
    4.4
    18.7
    7.8
    Week 20
    2.2
    14.6
    11.1
    Week 24
    2.2
    -7.8
    -2.6
    12. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Erythropoietin
    Description Percent change in erythropoietin at Weeks 8 and 20. The baseline erythropoietin value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 8 and 20

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 8
    -30.8
    -8.1
    -24.5
    Week 20
    -45.0
    8.5
    -4.4
    13. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Erythrocytes
    Description Percent change from baseline in erythrocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    5.2
    3.4
    3.4
    Week 4
    6.7
    3.6
    3.8
    Week 8
    3.6
    0.0
    3.0
    Week 12
    3.1
    3.6
    3.4
    Week 16
    0.0
    -6.9
    -2.9
    Week 20
    -3.3
    -3.4
    -3.4
    Week 24
    -8.0
    3.3
    0.0
    14. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Hematocrit
    Description Percent change from baseline in hematocrit, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    8.9
    4.0
    4.5
    Week 4
    7.4
    0.0
    3.4
    Week 8
    11.1
    -1.7
    4.0
    Week 12
    7.1
    1.8
    3.6
    Week 16
    5.9
    -4.2
    3.8
    Week 20
    7.1
    0.0
    0.0
    Week 24
    8.0
    2.3
    4.5
    15. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Ferritin
    Description Percent change from baseline in ferritin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    11.6
    8.8
    8.8
    Week 4
    19.1
    8.3
    13.6
    Week 8
    4.0
    30.4
    16.7
    Week 12
    -0.6
    26.4
    11.3
    Week 16
    0.1
    21.6
    6.7
    Week 20
    3.5
    13.6
    7.0
    Week 24
    -14.2
    15.4
    1.4
    16. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor
    Description Percent change from baseline in soluble transferrin receptor, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    4.0
    -4.9
    -4.8
    Week 4
    -1.4
    8.8
    0.7
    Week 8
    6.7
    11.0
    7.4
    Week 12
    0.8
    11.1
    10.7
    Week 16
    -0.1
    14.9
    1.3
    Week 20
    -1.8
    -0.7
    -1.2
    Week 24
    -3.5
    19.7
    -1.8
    17. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation
    Description Percent change from baseline in transferrin saturation, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    2.4
    13.5
    10.3
    Week 4
    36.4
    9.7
    10.5
    Week 8
    9.5
    -5.0
    -3.1
    Week 12
    11.9
    16.4
    14.1
    Week 16
    -7.2
    -13.5
    -10.4
    Week 20
    -2.5
    -20.8
    -13.3
    Week 24
    -8.3
    -20.8
    -11.9
    18. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity
    Description Percent change from baseline in unsaturated iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    0.0
    -5.1
    0.0
    Week 4
    -4.0
    0.0
    -1.0
    Week 8
    6.4
    0.0
    0.0
    Week 12
    2.9
    -18.4
    -1.6
    Week 16
    4.3
    0.0
    2.6
    Week 20
    16.5
    5.1
    14.2
    Week 24
    12.0
    6.9
    12.0
    19. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Platelets
    Description Percent change from baseline in platelets, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    21.4
    -24.4
    -9.5
    Week 4
    0.0
    -29.7
    -26.3
    Week 8
    19.7
    -33.6
    -12.0
    Week 12
    24.1
    -27.7
    -11.4
    Week 16
    17.8
    -26.1
    -6.2
    Week 20
    31.0
    -36.2
    -14.3
    Week 24
    38.9
    -22.5
    -15.3
    20. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Leukocytes
    Description Percent change from baseline in leukocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 4, 8, 12, 16, 20 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    11.6
    -24.9
    -14.9
    Week 4
    6.8
    -4.7
    0.7
    Week 8
    34.3
    -0.9
    8.9
    Week 12
    8.0
    -15.4
    5.4
    Week 16
    42.0
    -6.7
    15.2
    Week 20
    44.7
    -27.5
    16.3
    Week 24
    53.0
    18.3
    27.1
    21. Secondary Outcome
    Title Change in Markers of Iron Metabolism and Anemia - Blasts
    Description Change from baseline in % blasts at Weeks 2 and 4. The baseline % blasts value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2 and 4

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    0
    3.0
    3.0
    Week 4
    0
    1.0
    1.0
    22. Secondary Outcome
    Title Change in Liver Iron Content
    Description Percent change from baseline in liver iron content assessed by MRI. The baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame Measured at Week 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Median (Inter-Quartile Range) [% Change from baseline]
    4.7
    53.3
    22.3
    23. Secondary Outcome
    Title Change in Pharmacodynamics Biomarker - pSTAT3
    Description Percent change in %pSTAT stimulated CD3+/4+ T cell at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
    Time Frame On Day 1 and at Weeks 4 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Day 1 - 2 hours postdose
    -15.8
    -13.5
    -14.3
    Day 1 - 4 hours postdose
    -17.1
    -10.6
    -12.8
    Day 1 - 6 hours postdose
    -9.0
    -4.3
    -7.1
    Week 4 - predose
    -0.9
    -2.9
    -2.0
    Week 4 - 2 hours postdose
    -18.9
    -20.0
    -20.0
    Week 4 - 4 hours postdose
    -19.8
    -14.1
    -14.1
    Week 4 - 6 hours postdose
    -12.1
    -9.1
    -9.1
    Week 24 - predose
    -4.6
    -0.3
    -2.8
    Week 24 - 2 hours postdose
    -31.2
    -10.7
    -22.7
    Week 24 - 4 hours postdose
    -30.6
    -14.4
    -22.6
    Week 24 - 6 hours postdose
    -17.0
    -10.1
    -13.4
    24. Secondary Outcome
    Title Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio
    Description Percent change in %pSTAT/%tSTAT Stimulated CD3+/4+ T cell ratio at Day 1 (postdose), Week 4 and Week 24. The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
    Time Frame On Day 1 and at Weeks 4 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Day 1 - 2 hours postdose
    -13.2
    -15.5
    -13.4
    Day 1 - 4 hours postdose
    -9.6
    -9.7
    -9.7
    Day 1 - 6 hours postdose
    -9.1
    -3.7
    -4.6
    Week 4 - predose
    0.5
    5.0
    4.8
    Week 4 - 2 hours postdose
    -14.3
    -9.1
    -13.2
    Week 4 - 4 hours postdose
    3.0
    -13.4
    -13.4
    Week 4 - 6 hours postdose
    12.5
    -6.1
    -6.1
    Week 24 - predose
    -5.7
    -3.5
    -4.4
    Week 24 - 2 hours postdose
    -18.7
    -7.6
    -16.2
    Week 24 - 4 hours postdose
    -21.4
    -11.5
    -15.4
    Week 24 - 6 hours postdose
    -18.4
    -6.5
    -11.1
    25. Secondary Outcome
    Title Change in Inflammatory Markers - C-Reactive Protein (CRP)
    Description Percent change in C-reactive protein at Weeks 2, 12 and 24. The baseline C-reactive protein value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
    Time Frame At Weeks 2, 12 and 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Transfusion Independence Responders Transfusion Independence Non-Responders Total
    Arm/Group Description Subjects who became transfusion independent by Week 24 Subjects who did not become transfusion independent by Week 24 All enrolled subjects
    Measure Participants 14 27 41
    Week 2
    -68.7
    -53.7
    -55.6
    Week 12
    -67.8
    -43.4
    -48.9
    Week 24
    -59.8
    -47.1
    -54.8

    Adverse Events

    Time Frame From the first dose of momelotinib until 30 days following the last dose.
    Adverse Event Reporting Description All adverse events summarized were treatment-emergent, defined as any adverse event with an onset date on or after the momelotinib start date and no later than 30 days after permanent discontinuation of momelotinib or any adverse event leading to premature discontinuation of momelotinib.
    Arm/Group Title Momelotinib (MMB)
    Arm/Group Description Subjects received oral MMB at a starting dose of 200 mg once daily for 24 weeks (± 7 days) on study.
    All Cause Mortality
    Momelotinib (MMB)
    Affected / at Risk (%) # Events
    Total 3/41 (7.3%)
    Serious Adverse Events
    Momelotinib (MMB)
    Affected / at Risk (%) # Events
    Total 14/41 (34.1%)
    Blood and lymphatic system disorders
    Anemia 3/41 (7.3%)
    Neutropenia 1/41 (2.4%)
    Cardiac disorders
    Atrial fibrillation 1/41 (2.4%)
    Cardiac arrest 1/41 (2.4%)
    Gastrointestinal disorders
    Colitis 1/41 (2.4%)
    Small intestinal obstruction 1/41 (2.4%)
    General disorders
    Asthenia 1/41 (2.4%)
    Death 1/41 (2.4%)
    Pyrexia 1/41 (2.4%)
    Hepatobiliary disorders
    Cholecystitis 1/41 (2.4%)
    Infections and infestations
    Lung infection 2/41 (4.9%)
    Pneumonia 1/41 (2.4%)
    Sepsis 1/41 (2.4%)
    Injury, poisoning and procedural complications
    Transfusion reaction 1/41 (2.4%)
    Investigations
    Hepatic enzyme increased 1/41 (2.4%)
    Musculoskeletal and connective tissue disorders
    Bone pain 1/41 (2.4%)
    Nervous system disorders
    Presyncope 2/41 (4.9%)
    Dizziness 1/41 (2.4%)
    Metabolic encephalopathy 1/41 (2.4%)
    Renal and urinary disorders
    Acute kidney injury 3/41 (7.3%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/41 (2.4%)
    Respiratory failure 1/41 (2.4%)
    Vascular disorders
    Hypotension 2/41 (4.9%)
    Other (Not Including Serious) Adverse Events
    Momelotinib (MMB)
    Affected / at Risk (%) # Events
    Total 36/41 (87.8%)
    Blood and lymphatic system disorders
    Thrombocytopenia 7/41 (17.1%)
    Neutropenia 5/41 (12.2%)
    Gastrointestinal disorders
    Diarrhoea 10/41 (24.4%)
    Nausea 9/41 (22%)
    Vomiting 7/41 (17.1%)
    Abdominal pain 6/41 (14.6%)
    Constipation 3/41 (7.3%)
    General disorders
    Fatigue 8/41 (19.5%)
    Chills 3/41 (7.3%)
    Infections and infestations
    Urinary tract infection 6/41 (14.6%)
    Injury, poisoning and procedural complications
    Contusion 5/41 (12.2%)
    Fall 4/41 (9.8%)
    Investigations
    Blood creatinine increased 3/41 (7.3%)
    Metabolism and nutrition disorders
    Decreased appetite 4/41 (9.8%)
    Hyperuricaemia 4/41 (9.8%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain 3/41 (7.3%)
    Nervous system disorders
    Dizziness 6/41 (14.6%)
    Headache 6/41 (14.6%)
    Peripheral sensory neuropathy 3/41 (7.3%)
    Renal and urinary disorders
    Pollakiuria 3/41 (7.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 12/41 (29.3%)
    Dyspnoea 5/41 (12.2%)
    Nasal congestion 3/41 (7.3%)
    Skin and subcutaneous tissue disorders
    Pruritus 7/41 (17.1%)
    Night sweats 3/41 (7.3%)
    Vascular disorders
    Hypotension 3/41 (7.3%)

    Limitations/Caveats

    Pharmacokinetics parameters were removed as an analysis endpoint in the SAP due to the sparse PK samples collection. Change in circulating cytokine and inflammatory markers were limited to CRP as an analysis endpoint in the SAP.

    More Information

    Certain Agreements

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

    Most restrictive: Site may not present or publish results of Trial without advance written notice of Sponsor or two years after completion of Trial at all participating sites. Site must submit all proposed publications or presentations to Sponsor for review. Sponsor can review communications prior to public release and embargo trial results communications for a period between 75 and 180 days from submission to Sponsor for review. Sponsor has right to request Site remove Confidential Information.

    Results Point of Contact

    Name/Title Dr. Barbara Klencke
    Organization Sierra Oncology, Inc.
    Phone 1-604-558-6536
    Email bklencke@sierraoncology.com
    Responsible Party:
    Sierra Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02515630
    Other Study ID Numbers:
    • GS-US-352-1672
    First Posted:
    Aug 5, 2015
    Last Update Posted:
    Jan 20, 2021
    Last Verified:
    Jan 1, 2021