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Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)

Sponsor
Global Blood Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03036813
Collaborator
(none)
449
Enrollment
62
Locations
3
Arms
34.2
Actual Duration (Months)
7.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This is a randomized, placebo-controlled, double blind, parallel group, multicenter study of participants, age 12 to 65 years, with SCD. The key purpose for the study is to establish efficacy and safety of voxelotor as compared with placebo.

Study Design

Study Type:
Interventional
Actual Enrollment :
449 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Masking Description:
This study is a double-blind study.
Primary Purpose:
Treatment
Official Title:
A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease
Actual Study Start Date :
Dec 1, 2016
Actual Primary Completion Date :
Oct 8, 2019
Actual Study Completion Date :
Oct 8, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Dose 1

voxelotor

Drug: voxelotor
Other Names:
  • GBT440

    		•
    Active Comparator: Dose 2

    voxelotor

    Drug: voxelotor
    Other Names:
  • GBT440

    		•
    Placebo Comparator: Placebo

    Placebo

    Other: Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24 [Baseline to Week 24]

      Number of participants with increase in Hb >1 g/dL from Baseline to Week 24

    Secondary Outcome Measures

    1. Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate [Baseline to Week 72]

      Number of Vaso-Occlusive Crisis (VOC) events averaged per year.

    2. Percentage Change From Baseline in Hemolysis Measures [Baseline to Week 24]

      Percentage change from Baseline to week 24 in unconjugated bilirubin

    3. Percentage Change From Baseline in Hemolysis Measures [Baseline to Week 24]

      Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory.

    4. Percentage Change From Baseline in Hemolysis Measures [Baseline to Week 24]

      Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).

    5. Percentage Change From Baseline in Hemolysis Measures [Baseline to Week 24]

      Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Male or female study participants with sickle cell disease

    2. Participants have had at least 1 episode of vaso-occlusive crisis (VOC) in the past 12 months.

    3. Age 12 to 65 years

    4. Hemoglobin (Hb) ≥5.5 and ≤10.5 g/dL during screening

    5. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at least 3 months prior to signing the ICF.

    Exclusion Criteria:

    1. More than 10 VOCs within the past 12 months that required a hospital, emergency room or clinic visit

    2. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 60 days of signing the ICF

    3. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF (i.e., a vaso-occlusive event cannot be within 14 days prior to signing the ICF)

    4. Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × upper limit of normal

    5. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30 mL/min/1.73 m^2 or on chronic dialysis

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35205
    2 Mobile Alabama United States 36693
    3 Little Rock Arkansas United States 72204
    4 Oakland California United States 94609
    5 Miami Florida United States 33136
    6 Atlanta Georgia United States 30342
    7 Chicago Illinois United States 60612
    8 Indianapolis Indiana United States 46260
    9 Baton Rouge Louisiana United States 70808
    10 New Orleans Louisiana United States 70112
    11 Baltimore Maryland United States 21287
    12 Bethesda Maryland United States 20817
    13 Boston Massachusetts United States 02115
    14 Boston Massachusetts United States 02118
    15 Detroit Michigan United States 48201
    16 Newark New Jersey United States 07112
    17 Bronx New York United States 11501
    18 New York New York United States 10032
    19 Chapel Hill North Carolina United States 27514
    20 Durham North Carolina United States 27710
    21 Greenville North Carolina United States 27834
    22 Oklahoma City Oklahoma United States 73112
    23 Philadelphia Pennsylvania United States 19107
    24 Pittsburgh Pennsylvania United States 15219
    25 Charleston South Carolina United States 29425
    26 Memphis Tennessee United States 38105
    27 Nashville Tennessee United States 37232
    28 Houston Texas United States 77030
    29 Richmond Virginia United States 23298
    30 Toronto Canada M5G 2C4
    31 Alexandria Egypt 21131
    32 Cairo Egypt 11566
    33 Cairo Egypt
    34 Zagazig Egypt 44519
    35 Créteil France 94010
    36 Paris France 75743
    37 Paris France 75908
    38 Monza Milano Italy 20900
    39 Padova Italy 35128
    40 Verona Italy 37134
    41 Kingston Jamaica JMAAW15
    42 Nairobi Kenya 42325-00100
    43 Nairobi Kenya 47855
    44 Nairobi Kenya 59857-00200
    45 Siaya Kenya 144-40600
    46 Beirut Lebanon 11072020
    47 Beirut Lebanon 1136044
    48 Nini Hospital s.a.l Tripoli Lebanon 1434
    49 Amsterdam Netherlands 1105 AZ
    50 Den Haag Netherlands 2545 CH
    51 Rotterdam Netherlands 3015 AA
    52 Muscat Oman 123
    53 Adana Turkey 01130
    54 Kayseri Turkey 38039
    55 Mersin Turkey 33342
    56 London United Kingdom E11BB
    57 London United Kingdom E96SR
    58 London United Kingdom SE17EH
    59 London United Kingdom SE59NU
    60 London United Kingdom W12 0HS
    61 London United Kingdom WC1N3BG
    62 Manchester United Kingdom M13 9WL

    Sponsors and Collaborators

    • Global Blood Therapeutics

    Investigators

    • Study Director: Margaret Tonda, PharmD, Global Blood Therapeutics, Inc

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Global Blood Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03036813
    Other Study ID Numbers:
    • GBT440-031
    First Posted:
    Jan 30, 2017
    Last Update Posted:
    Jan 7, 2021
    Last Verified:
    Jan 1, 2021
    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
    Additional relevant MeSH terms:
    Anemia, Sickle Cell

    Study Results

    Participant Flow

    Recruitment Details Overall, 449 subjects were screened for this study at 60 study sites. Between January 2017 and May 2018, a total of 274 subjects were randomized at 58 study sites across 12 countries. All 274 randomized subjects were included in the ITT Population. A total of 271 subjects received study drug and were included in the Safety Population.
    Pre-assignment Detail Screening procedures were done within 35 days of randomization to assess eligibility.
    Arm/Group Title Voxelotor 900mg Voxelotor 1500mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily for 72 weeks. Participants received voxelotor 1500 mg administered orally, once daily for 72 weeks. Matching placebo; administered orally, once daily for 72 weeks.
    Period Title: Overall Study
    STARTED 92 90 92
    COMPLETED 70 63 66
    NOT COMPLETED 22 27 26

    Baseline Characteristics

    Arm/Group Title Voxelotor 900mg Voxelotor 1500mg Placebo Total
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily for 72 weeks. Participants received voxelotor 1500 mg; administered orally, once daily for 72 weeks Matching Placebo; administered orally, once daily for 72 weeks Total of all reporting groups
    Overall Participants 92 90 92 274
    Age, Customized (Count of Participants)
    12 to < 18
    15
    16.3%
    14
    15.6%
    17
    18.5%
    46
    16.8%
    >=18 to < 65
    77
    83.7%
    76
    84.4%
    75
    81.5%
    228
    83.2%
    Sex: Female, Male (Count of Participants)
    Female
    51
    55.4%
    58
    64.4%
    50
    54.3%
    159
    58%
    Male
    41
    44.6%
    32
    35.6%
    42
    45.7%
    115
    42%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    4.3%
    3
    3.3%
    3
    3.3%
    10
    3.6%
    Not Hispanic or Latino
    86
    93.5%
    82
    91.1%
    85
    92.4%
    253
    92.3%
    Unknown or Not Reported
    2
    2.2%
    5
    5.6%
    4
    4.3%
    11
    4%
    Race/Ethnicity, Customized (Count of Participants)
    Arab/Middle Eastern
    19
    20.7%
    15
    16.7%
    18
    19.6%
    52
    19%
    Black or African American
    60
    65.2%
    59
    65.6%
    63
    68.5%
    182
    66.4%
    White
    6
    6.5%
    7
    7.8%
    3
    3.3%
    16
    5.8%
    Asian
    0
    0%
    1
    1.1%
    0
    0%
    1
    0.4%
    Other
    4
    4.3%
    2
    2.2%
    5
    5.4%
    11
    4%
    Multiple
    2
    2.2%
    5
    5.6%
    3
    3.3%
    10
    3.6%
    Missing/ Not Specified
    1
    1.1%
    1
    1.1%
    0
    0%
    2
    0.7%
    Region of Enrollment (participants) [Number]
    Europe
    19
    20.7%
    19
    21.1%
    18
    19.6%
    56
    20.4%
    North America
    36
    39.1%
    34
    37.8%
    35
    38%
    105
    38.3%
    Egypt
    15
    16.3%
    16
    17.8%
    13
    14.1%
    44
    16.1%
    Kenya
    17
    18.5%
    14
    15.6%
    18
    19.6%
    49
    17.9%
    Jamaica
    0
    0%
    2
    2.2%
    2
    2.2%
    4
    1.5%
    Oman
    2
    2.2%
    2
    2.2%
    5
    5.4%
    9
    3.3%
    Lebanon
    3
    3.3%
    3
    3.3%
    1
    1.1%
    7
    2.6%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24
    Description Number of participants with increase in Hb >1 g/dL from Baseline to Week 24
    Time Frame Baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    All randomized subject (ITT population).
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg administered orally, once daily Participants received voxelotor 1500mg; administered orally, once daily Participants received matching placebo; administered orally, once daily
    Measure Participants 92 90 92
    Count of Participants [Participants]
    30
    32.6%
    46
    51.1%
    6
    6.5%
    2. Secondary Outcome
    Title Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate
    Description Number of Vaso-Occlusive Crisis (VOC) events averaged per year.
    Time Frame Baseline to Week 72

    Outcome Measure Data

    Analysis Population Description
    Population excludes 3 subjects (1 in the placebo group and 2 in the voxelotor 1500-mg group) who were not treated.
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily Participants received voxelotor 1500 mg; administered orally, once daily Participants received matching placebo; administered orally, once daily
    Measure Participants 92 88 91
    Mean (95% Confidence Interval) [Events per year]
    2.4
    2.4
    2.8
    3. Secondary Outcome
    Title Percentage Change From Baseline in Hemolysis Measures
    Description Percentage change from Baseline to week 24 in unconjugated bilirubin
    Time Frame Baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis population includes all randomized patients with a baseline value and at least one post-baseline value
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily Participants received voxelotor 1500 mg; administered orally, once daily Participants received matching placebo; administered orally, once daily
    Measure Participants 88 85 85
    Least Squares Mean (Standard Error) [percentage change]
    -20.1
    (3.41)
    -29.1
    (3.46)
    -2.8
    (3.51)
    4. Secondary Outcome
    Title Percentage Change From Baseline in Hemolysis Measures
    Description Percentage change from Baseline to week 24 in the absolute reticulocyte which is used to estimate the degree of effective erythropoiesis. This values is important in Sickle Cell Disease and was reported by the central laboratory.
    Time Frame Baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily Participants received voxelotor 1500 mg; administered orally, once daily Participants will receive matching placebo; administered orally, once daily
    Measure Participants 92 88 91
    Least Squares Mean (Standard Error) [percentage change]
    4.7
    (5.13)
    -6.4
    (5.17)
    4.7
    (5.19)
    5. Secondary Outcome
    Title Percentage Change From Baseline in Hemolysis Measures
    Description Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).
    Time Frame Baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily Participants received voxelotor 1500 mg; administered orally, once daily Participants received matching placebo; administered orally, once daily
    Measure Participants 92 88 91
    Least Squares Mean (Standard Error) [Percentage Change]
    -1.4
    (4.65)
    -18.0
    (4.70)
    6.8
    (4.73)
    6. Secondary Outcome
    Title Percentage Change From Baseline in Hemolysis Measures
    Description Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)
    Time Frame Baseline to Week 24

    Outcome Measure Data

    Analysis Population Description
    Analysis population includes all randomized patients with a baseline value and at least one post-baseline value
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg; administered orally, once daily Participants received voxelotor 1500 mg; administered orally, once daily Participants received matching placebo; administered orally, once daily
    Measure Participants 90 88 87
    Least Squares Mean (Standard Error) [Percentage Change]
    1.6
    (3.68)
    -4.6
    (3.69)
    3.0
    (3.75)

    Adverse Events

    Time Frame 72 Weeks
    Adverse Event Reporting Description Non-sickle cell disease (Non-SCD) related Adverse Events.
    Arm/Group Title Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Arm/Group Description Participants received voxelotor 900 mg, administered orally, once daily Participants received voxelotor 1500 mg administered orally, once daily Participants received matching placebo; administered orally, once daily
    All Cause Mortality
    Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/92 (2.2%) 2/88 (2.3%) 2/91 (2.2%)
    Serious Adverse Events
    Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/92 (21.7%) 25/88 (28.4%) 23/91 (25.3%)
    Blood and lymphatic system disorders
    Anaemia 3/92 (3.3%) 3 0/88 (0%) 0 2/91 (2.2%) 2
    Hypersplenism 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Reticulocytopenia 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Thrombocytopenia 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Haemolytic anaemia 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Splenic infarction 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Thrombocytosis 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Cardiac disorders
    Cardiac failure high output 0/92 (0%) 0 1/88 (1.1%) 2 0/91 (0%) 0
    Supraventricular tachycardia 1/92 (1.1%) 2 0/88 (0%) 0 0/91 (0%) 0
    Cardiac arrest 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Eye disorders
    Blindness 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Retinal haemorrhage 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Vitreous haemorrhage 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Gastrointestinal disorders
    Gastritis 2/92 (2.2%) 2 0/88 (0%) 0 0/91 (0%) 0
    Nausea 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Diarrhoea 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Gastritis haemorrhagic 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Odynophagia 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    General disorders
    Pyrexia 3/92 (3.3%) 4 2/88 (2.3%) 2 3/91 (3.3%) 3
    Non-cardiac chest pain 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Peripherial swelling 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Hepatobiliary disorders
    Cholecystitis 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Hepatic sequestration 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Cholelithiasis 1/92 (1.1%) 1 0/88 (0%) 0 1/91 (1.1%) 1
    Hepatitis acute 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Immune system disorders
    Drug hypersensitivity 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Infections and infestations
    Malaria 3/92 (3.3%) 5 1/88 (1.1%) 1 0/91 (0%) 0
    Upper respiratory tract infection 0/92 (0%) 0 1/88 (1.1%) 1 1/91 (1.1%) 1
    Appendicitis 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Brain abscess 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Gastrointestinal viral infection 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Pulmonary sepsis 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Tonsillitis 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Cellulitis 1/92 (1.1%) 1 0/88 (0%) 0 1/91 (1.1%) 1
    Lower respiratory tract infection 1/92 (1.1%) 1 0/88 (0%) 0 1/91 (1.1%) 1
    Urinary tract infection 1/92 (1.1%) 1 0/88 (0%) 0 1/91 (1.1%) 1
    Pharyngitis 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Sepsis 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Sepsis syndrome 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Gastroenteritis 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Gastroenteritis viral 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Influenza 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Lung infection 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Injury, poisoning and procedural complications
    Patella fracture 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Lower limb fracture 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Spinal compression fracture 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Medication error 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Investigations
    Oxygen saturation decreased 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Haemoglobin decreased 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Metabolism and nutrition disorders
    Gout 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Hypokalaemia 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Type 2 diabetes mellitus 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 2/92 (2.2%) 2 0/88 (0%) 0 1/91 (1.1%) 1
    Arthralgia 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Arthritis 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Back pain 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Pain in extemity 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Costochondritis 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Musculoskeletal pain 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Nervous system disorders
    Encephalopathy 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Headache 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Seizure 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Cerebrovascular accident 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Cerebral microhaemorrhage 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Depressed level of consciousness 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Hyperaesthesia 0/92 (0%) 0 0/88 (0%) 0 1/91 (1.1%) 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 0/92 (0%) 0 2/88 (2.3%) 2 0/91 (0%) 0
    Pulmonary embolism 0/92 (0%) 0 2/88 (2.3%) 2 1/91 (1.1%) 1
    Respiratory failure 0/92 (0%) 0 1/88 (1.1%) 1 1/91 (1.1%) 1
    Acute respiratory failure 0/92 (0%) 0 1/88 (1.1%) 1 0/91 (0%) 0
    Skin and subcutaneous tissue disorders
    Rash generalised 1/92 (1.1%) 1 0/88 (0%) 0 0/91 (0%) 0
    Surgical and medical procedures
    Cholecystectomy 0/92 (0%) 0 1/88 (1.1%) 1 1/91 (1.1%) 1
    Other (Not Including Serious) Adverse Events
    Voxelotor 900 mg Voxelotor 1500 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 85/92 (92.4%) 85/88 (96.6%) 81/91 (89%)
    Blood and lymphatic system disorders
    Anaemia 6/92 (6.5%) 9 4/88 (4.5%) 4 2/91 (2.2%) 2
    Gastrointestinal disorders
    Diarrhoea 17/92 (18.5%) 24 20/88 (22.7%) 22 10/91 (11%) 12
    Nausea 17/92 (18.5%) 21 16/88 (18.2%) 21 9/91 (9.9%) 17
    Abdominal pain 13/92 (14.1%) 15 13/88 (14.8%) 17 10/91 (11%) 12
    Vomiting 13/92 (14.1%) 20 11/88 (12.5%) 17 15/91 (16.5%) 24
    Abdominal pain upper 14/92 (15.2%) 19 8/88 (9.1%) 9 6/91 (6.6%) 10
    Constipation 9/92 (9.8%) 9 6/88 (6.8%) 7 9/91 (9.9%) 9
    Gastritis 5/92 (5.4%) 7 3/88 (3.4%) 8 4/91 (4.4%) 4
    General disorders
    Pain 15/92 (16.3%) 27 15/88 (17%) 27 18/91 (19.8%) 22
    Fatigue 13/92 (14.1%) 16 12/88 (13.6%) 14 12/91 (13.2%) 15
    Pyrexia 10/92 (10.9%) 13 11/88 (12.5%) 13 4/91 (4.4%) 5
    Non-cardiac chest pain 13/92 (14.1%) 15 9/88 (10.2%) 10 10/91 (11%) 10
    Hepatobiliary disorders
    Ocular icterus 9/92 (9.8%) 15 6/88 (6.8%) 7 8/91 (8.8%) 14
    Infections and infestations
    Upper respiratory tract infection 22/92 (23.9%) 26 12/88 (13.6%) 13 13/91 (14.3%) 18
    Urinary tract infection 5/92 (5.4%) 8 9/88 (10.2%) 10 13/91 (14.3%) 15
    Tonsillitis 3/92 (3.3%) 5 5/88 (5.7%) 7 8/91 (8.8%) 10
    Malaria 2/92 (2.2%) 5 5/88 (5.7%) 8 3/91 (3.3%) 6
    Influenza 4/92 (4.3%) 5 3/88 (3.4%) 3 5/91 (5.5%) 6
    Gastroenteritis 6/92 (6.5%) 6 2/88 (2.3%) 2 3/91 (3.3%) 5
    Metabolism and nutrition disorders
    Decreased appetite 6/92 (6.5%) 6 2/88 (2.3%) 2 0/91 (0%) 0
    Hypokalaemia 3/92 (3.3%) 3 2/88 (2.3%) 4 5/91 (5.5%) 5
    Musculoskeletal and connective tissue disorders
    Arthralgia 14/92 (15.2%) 24 18/88 (20.5%) 33 13/91 (14.3%) 17
    Back pain 12/92 (13%) 25 15/88 (17%) 17 12/91 (13.2%) 16
    Pain in extremity 20/92 (21.7%) 33 12/88 (13.6%) 19 19/91 (20.9%) 22
    Musculoskeletal pain 4/92 (4.3%) 4 6/88 (6.8%) 6 4/91 (4.4%) 4
    Bone pain 1/92 (1.1%) 5 5/88 (5.7%) 9 8/91 (8.8%) 22
    Musculoskeletal chest pain 0/92 (0%) 0 2/88 (2.3%) 3 5/91 (5.5%) 5
    Nervous system disorders
    Headache 20/92 (21.7%) 22 27/88 (30.7%) 33 23/91 (25.3%) 34
    Dizziness 8/92 (8.7%) 10 4/88 (4.5%) 4 9/91 (9.9%) 9
    Respiratory, thoracic and mediastinal disorders
    Cough 6/92 (6.5%) 7 8/88 (9.1%) 10 10/91 (11%) 11
    Oropharyngeal pain 1/92 (1.1%) 1 7/88 (8%) 9 1/91 (1.1%) 1
    Dyspnoea 5/92 (5.4%) 5 2/88 (2.3%) 2 4/91 (4.4%) 6
    Skin and subcutaneous tissue disorders
    Rash 5/92 (5.4%) 5 6/88 (6.8%) 9 8/91 (8.8%) 8
    Pruritus 5/92 (5.4%) 8 4/88 (4.5%) 4 3/91 (3.3%) 6

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Margaret Tonda, PharmD, Sr. Director, Clinical Science
    Organization Global Blood Therapeutics
    Phone (650) 741-7761
    Email mtonda@gbt.com
    Responsible Party:
    Global Blood Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03036813
    Other Study ID Numbers:
    • GBT440-031
    First Posted:
    Jan 30, 2017
    Last Update Posted:
    Jan 7, 2021
    Last Verified:
    Jan 1, 2021