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

    Summary
    EudraCT number
    		 2016-003370-40
    Trial protocol
    		 GB   NL   FR   IT  
    Global end of trial date
    08 Oct 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    21 Mar 2021
    First version publication date
    21 Mar 2021
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GBT440-031
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03036813
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Global Blood Therapeutics, Inc.
    Sponsor organisation address
    181 Oyster Point Blvd, South San Francisco, United States, 94080
    Public contact
    Margaret Tonda, Global Blood Therapeutics, Inc., 1 650.741.7761, mtonda@gbt.com
    Scientific contact
    Sr. Director, Clinical Science, Global Blood Therapeutics, Inc., 1 650.741.7761, mtonda@gbt.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002356-PIP02-20
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    22 Nov 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    08 Oct 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Oct 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to assess the efficacy of voxelotor (GBT440) in adolescents and adults with Sickle Cell Disease (SCD) as measured by improvement in hemoglobin.
    Protection of trial subjects
    1. All approved therapies for SCD were allowed under this protocol including pain control, hydroxycarbamide (HU) therapy, L-glutamine, and blood transfusions. Other concomitant medications specifically permitted by the protocol included penicillin, folic acid, and codeine, as these are medications commonly used by subjects with SCD. In addition, the use of combined (estrogen- and progestogen-containing) or progestogen-only hormonal contraception associated with inhibition of ovulation was also permitted. All subjects used at least 1 concomitant medication. 2. Patients may be removed from the study at any time at the discretion of the investigator per his/her clinical judgement for reasons including severe AE. 3. An independent DSMB monitored the safety and conduct of the study.
    Background therapy
    		 All approved therapies for SCD were allowed under this protocol including pain control, HU therapy, L-glutamine, and blood transfusions. Other concomitant medications specifically permitted by the protocol included penicillin, folic acid, and codeine, as these are medications commonly used by subjects with SCD.
    Evidence for comparator
    		 This study used placebo as a comparator on the background of best clinical standard-of-care treatment. All approved therapies for SCD were allowed under the protocol; none were withheld. This included pain control, HU, L-glutamine, and blood transfusions. Agreeing to placebo treatment did not place subjects at any increased risk, because no standard of care (SOC) therapies were withheld as a result.
    Actual start date of recruitment
    13 Dec 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 101
    Country: Number of subjects enrolled
    Kenya: 49
    Country: Number of subjects enrolled
    Egypt: 44
    Country: Number of subjects enrolled
    Turkey: 12
    Country: Number of subjects enrolled
    Oman: 9
    Country: Number of subjects enrolled
    Lebanon: 7
    Country: Number of subjects enrolled
    Canada: 4
    Country: Number of subjects enrolled
    Jamaica: 4
    Country: Number of subjects enrolled
    Netherlands: 8
    Country: Number of subjects enrolled
    United Kingdom: 32
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Italy: 1
    Worldwide total number of subjects
    274
    EEA total number of subjects
    44
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    46
    Adults (18-64 years)
    228
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    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
    Screening details
    		 Screening procedures were done within 35 days of randomization to assess eligibility.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Carer, Assessor
    Blinding implementation details
    This study was a double-blind study. The voxelotor and placebo capsules or tablets were matched for shape, size, and color. All individuals involved in the conduct of the study (ie, site staff and participants, Investigator, CRO personnel, Sponsor personnel) were blinded to randomized treatment assignment. Drug Supply personnel remained unblinded throughout the study. Other sponsor and CRO personnel may be unblinded as required per Regulatory reporting requirements of SUSARS.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Voxelotor 900mg
    Arm description
    		 Participants received voxelotor 900mg; administered orally, once daily for 72 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Voxelotor 900mg
    Investigational medicinal product code
    Other name
    GBT440
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    900mg administered orally once a day

    Arm title
    		 Voxelotor 1500mg
    Arm description
    		 Participants received voxelotor 1500mg administered orally, once daily for 72 weeks
    Arm type
    		 Experimental

    Investigational medicinal product name
    Voxelotor 1500mg
    Investigational medicinal product code
    Other name
    GBT440
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1500mg administered orally once a day

    Arm title
    		 Placebo
    Arm description
    		 Matching placebo; administered orally, once daily for 72 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		Voxelotor 900mg Voxelotor 1500mg Placebo
    Started
    92
    90
    92
    Completed
    70
    63
    66
    Not completed
    22
    27
    26
         Consent withdrawn by subject
    12
    6
    10
         Physician decision
    2
    1
    1
         Non-Compliance
    1
    5
    3
         Reason Not Categorized
    -
    3
    5
         Pregnancy
    -
    -
    1
         Adverse event
    6
    11
    6
         Lost to follow-up
    1
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Voxelotor 900mg
    Reporting group description
    		 Participants received voxelotor 900mg; administered orally, once daily for 72 weeks.

    Reporting group title
    Voxelotor 1500mg
    Reporting group description
    		 Participants received voxelotor 1500mg administered orally, once daily for 72 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo; administered orally, once daily for 72 weeks.

    Reporting group values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo Total
    Number of subjects
    		 92 90 92 274
    Age categorical
    Overall Number of Baseline Participants
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 15 14 17 46
        Adults (18-64 years)
    		 77 76 75 228
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Gender categorical
    Sex: Female, Male
    Units: Subjects
        Female
    		 51 58 50 159
        Male
    		 41 32 42 115

    End points

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    End points reporting groups
    Reporting group title
    Voxelotor 900mg
    Reporting group description
    		 Participants received voxelotor 900mg; administered orally, once daily for 72 weeks.

    Reporting group title
    Voxelotor 1500mg
    Reporting group description
    		 Participants received voxelotor 1500mg administered orally, once daily for 72 weeks

    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo; administered orally, once daily for 72 weeks.

    Primary: Number of Participants with Increased in Hb>1 g/dL

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    End point title
    		 Number of Participants with Increased in Hb>1 g/dL
    End point description
    Number of participants with increased in Hb>1 g/dL from baseline to week 24.
    End point type
    Primary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Number of subjects analysed
    92
    90
    92
    Units: Count of Participants
    30
    46
    6
    Statistical analysis title
    		 Primary Endpoint (voxelotor 1500mg vs Placebo)
    Statistical analysis description
    Hemoglobin response of > 1 g/dl change from baseline was derived based on change from baseline to the average of the values for Weeks 20 and 24. Subjects with any of the following scenarios were counted as non-responders: 1) hemoglobin missing at both Weeks 20 and 24; 2) post-randomization HU use prior to Week 24 for subjects with no HU use at baseline; 3) received transfusion due to anemia within 8 weeks prior to Week 24 Hb assessment.
    Comparison groups
    Voxelotor 1500mg v Placebo
    Number of subjects included in analysis
    182
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in adjusted response rate
    Point estimate
    45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 33.4
         upper limit
    		 56.7
    Notes
    [1] - Comparison adjusted for baseline HU use, age group, and geographic region.

    Secondary: Percent Change From Baseline in Hemolysis Measures

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    End point title
    		 Percent Change From Baseline in Hemolysis Measures
    End point description
    Percentage change from baseline to week 24 in indirect bilirubin
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Number of subjects analysed
    88 [2]
    85 [3]
    85 [4]
    Units: Percent Change
        least squares mean (standard error)
    -20.1 ± 3.41
    -29.1 ± 3.46
    -2.8 ± 3.51
    Notes
    [2] - analysis pop includes all randomized with baseline and at least one baseline value
    [3] - analysis pop includes all randomized with baseline and at least one baseline value
    [4] - analysis pop includes all randomized with baseline and at least one baseline value
    No statistical analyses for this end point

    Secondary: Change from Baseline in Hemolysis Measures

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    End point title
    		 Change from Baseline in Hemolysis Measures
    End point description
    Percentage change from Baseline to Week 24 in reticulocytes percentage
    End point type
    Secondary
    End point timeframe
    Baseline to week 24
    End point values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Number of subjects analysed
    92
    88
    91
    Units: Percent Change
        least squares mean (standard error)
    -1.4 ± 4.65
    -18.0 ± 4.70
    6.8 ± 4.73
    No statistical analyses for this end point

    Secondary: Percentage Change From Baseline in Hemolysis Measures

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    End point title
    		 Percentage Change From Baseline in Hemolysis Measures
    End point description
    Percent Change from Baseline to week 24 in absolute reticulocytes.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Number of subjects analysed
    92
    88 [5]
    91 [6]
    Units: percent
        least squares mean (standard error)
    4.7 ± 5.13
    -6.4 ± 5.17
    4.17 ± 5.19
    Notes
    [5] - Population excludes 2 subjects that were not treated
    [6] - Population excludes 1 subject that was not treated.
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Hemolysis Measures

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    End point title
    		 Percent Change From Baseline in Hemolysis Measures
    End point description
    Percentage change from Baseline to Week 24 in Lactate Dehydrogenase (LDH)
    End point type
    Secondary
    End point timeframe
    Baseline to week 24
    End point values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Number of subjects analysed
    90 [7]
    88 [8]
    87 [9]
    Units: Percent Change
        least squares mean (standard error)
    1.6 ± 3.68
    -4.6 ± 3.69
    3.0 ± 3.75
    Notes
    [7] - analysis pop includes all randomized with baseline and at least one baseline value
    [8] - analysis pop includes all randomized with baseline and at least one baseline value
    [9] - analysis pop includes all randomized with baseline and at least one baseline value
    No statistical analyses for this end point

    Secondary: Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate

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    End point title
    		 Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate
    End point description
    Number of Vaso-Occlusive Crisis (VOC) events per year.
    End point type
    Secondary
    End point timeframe
    Baseline to week 72
    End point values
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Number of subjects analysed
    92
    88 [10]
    91 [11]
    Units: Adjusted Annualized Incidence Rate
        number (confidence interval 95%)
    2.4 (1.9 to 3.1)
    2.4 (1.8 to 3.1)
    2.8 (2.2 to 3.6)
    Notes
    [10] - Population excludes 2 subjects that were not treated
    [11] - Population excludes 1 subject that was not treated
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline to 72 Weeks
    Adverse event reporting additional description
    Non-sickle cell disease (Non-SCD) related Adverse Events. For number of deaths (all causes) the total of all deaths is reported (non-SCD and SCD related). For the number of deaths resulting from adverse events, only non-SCD adverse events are reported below.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Voxelotor 900mg
    Reporting group description
    		 Participants received voxelotor 900 mg; administered orally, once daily for 72 weeks.

    Reporting group title
    Voxelotor 1500mg
    Reporting group description
    		 Participants received voxelotor 1500 mg administered orally, once daily for 72 weeks.

    Reporting group title
    Placebo
    Reporting group description
    		 Matching placebo; administered orally, once daily for 72 weeks.

    Serious adverse events
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 92 (21.74%)
    25 / 88 (28.41%)
    23 / 91 (25.27%)
         number of deaths (all causes)
    2
    2
    2
         number of deaths resulting from adverse events
    1
    2
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cholecystectomy
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peripheral swelling
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 92 (3.26%)
    2 / 88 (2.27%)
    3 / 91 (3.30%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Death unknown etiology
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 92 (0.00%)
    2 / 88 (2.27%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 92 (0.00%)
    2 / 88 (2.27%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Lower limb fracture
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Medication error
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cardiac failure high output
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral microhaemorrhage
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalopathy
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Headache
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperaesthesia
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 92 (3.26%)
    0 / 88 (0.00%)
    2 / 91 (2.20%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemolytic anaemia
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypersplenism
         subjects affected / exposed
    0 / 92 (0.00%)
    2 / 88 (2.27%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reticulocytopenia
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thrombocytosis
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Blindness
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Retinal haemorrhage
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 92 (2.17%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis haemorrhagic
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Odynophagia
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic sequestration
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash generalized
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Costochondritis
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    2 / 92 (2.17%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal viral infection
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    0 / 92 (0.00%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malaria
         subjects affected / exposed
    3 / 92 (3.26%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis syndrome
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 92 (0.00%)
    1 / 88 (1.14%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    1 / 91 (1.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 92 (1.09%)
    0 / 88 (0.00%)
    0 / 91 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Voxelotor 900mg Voxelotor 1500mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    85 / 92 (92.39%)
    85 / 88 (96.59%)
    81 / 91 (89.01%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    8 / 92 (8.70%)
    4 / 88 (4.55%)
    9 / 91 (9.89%)
         occurrences all number
    10
    4
    9
    Headache
         subjects affected / exposed
    20 / 92 (21.74%)
    27 / 88 (30.68%)
    23 / 91 (25.27%)
         occurrences all number
    22
    33
    34
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    13 / 92 (14.13%)
    12 / 88 (13.64%)
    12 / 91 (13.19%)
         occurrences all number
    16
    14
    15
    Non-cardiac chest pain
         subjects affected / exposed
    13 / 92 (14.13%)
    9 / 88 (10.23%)
    10 / 91 (10.99%)
         occurrences all number
    15
    10
    10
    Pain
         subjects affected / exposed
    15 / 92 (16.30%)
    15 / 88 (17.05%)
    18 / 91 (19.78%)
         occurrences all number
    27
    27
    22
    Pyrexia
         subjects affected / exposed
    10 / 92 (10.87%)
    11 / 88 (12.50%)
    4 / 91 (4.40%)
         occurrences all number
    13
    13
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 92 (6.52%)
    4 / 88 (4.55%)
    2 / 91 (2.20%)
         occurrences all number
    9
    4
    2
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    13 / 92 (14.13%)
    13 / 88 (14.77%)
    10 / 91 (10.99%)
         occurrences all number
    15
    17
    12
    Abdominal pain upper
         subjects affected / exposed
    14 / 92 (15.22%)
    8 / 88 (9.09%)
    6 / 91 (6.59%)
         occurrences all number
    19
    9
    10
    Constipation
         subjects affected / exposed
    9 / 92 (9.78%)
    6 / 88 (6.82%)
    9 / 91 (9.89%)
         occurrences all number
    9
    7
    9
    Diarrhoea
         subjects affected / exposed
    17 / 92 (18.48%)
    20 / 88 (22.73%)
    10 / 91 (10.99%)
         occurrences all number
    24
    22
    12
    Gastritis
         subjects affected / exposed
    5 / 92 (5.43%)
    3 / 88 (3.41%)
    4 / 91 (4.40%)
         occurrences all number
    7
    8
    4
    Nausea
         subjects affected / exposed
    17 / 92 (18.48%)
    16 / 88 (18.18%)
    9 / 91 (9.89%)
         occurrences all number
    21
    21
    17
    Vomiting
         subjects affected / exposed
    13 / 92 (14.13%)
    11 / 88 (12.50%)
    15 / 91 (16.48%)
         occurrences all number
    20
    17
    24
    Hepatobiliary disorders
    Ocular icterus
         subjects affected / exposed
    9 / 92 (9.78%)
    6 / 88 (6.82%)
    8 / 91 (8.79%)
         occurrences all number
    15
    7
    14
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    6 / 92 (6.52%)
    8 / 88 (9.09%)
    10 / 91 (10.99%)
         occurrences all number
    7
    10
    11
    Dyspnoea
         subjects affected / exposed
    5 / 92 (5.43%)
    2 / 88 (2.27%)
    4 / 91 (4.40%)
         occurrences all number
    5
    2
    6
    Oropharyngeal pain
         subjects affected / exposed
    1 / 92 (1.09%)
    7 / 88 (7.95%)
    1 / 91 (1.10%)
         occurrences all number
    1
    9
    1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    5 / 92 (5.43%)
    4 / 88 (4.55%)
    3 / 91 (3.30%)
         occurrences all number
    8
    4
    6
    Rash
         subjects affected / exposed
    5 / 92 (5.43%)
    6 / 88 (6.82%)
    8 / 91 (8.79%)
         occurrences all number
    5
    9
    8
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    14 / 92 (15.22%)
    18 / 88 (20.45%)
    13 / 91 (14.29%)
         occurrences all number
    24
    33
    17
    Back pain
         subjects affected / exposed
    12 / 92 (13.04%)
    15 / 88 (17.05%)
    12 / 91 (13.19%)
         occurrences all number
    25
    17
    16
    Bone pain
         subjects affected / exposed
    1 / 92 (1.09%)
    5 / 88 (5.68%)
    8 / 91 (8.79%)
         occurrences all number
    5
    9
    22
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 92 (0.00%)
    2 / 88 (2.27%)
    5 / 91 (5.49%)
         occurrences all number
    0
    3
    5
    Musculoskeletal pain
         subjects affected / exposed
    4 / 92 (4.35%)
    6 / 88 (6.82%)
    4 / 91 (4.40%)
         occurrences all number
    4
    6
    4
    Pain in extremity
         subjects affected / exposed
    20 / 92 (21.74%)
    12 / 88 (13.64%)
    19 / 91 (20.88%)
         occurrences all number
    33
    19
    22
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    6 / 92 (6.52%)
    2 / 88 (2.27%)
    3 / 91 (3.30%)
         occurrences all number
    6
    2
    5
    Influenza
         subjects affected / exposed
    4 / 92 (4.35%)
    3 / 88 (3.41%)
    5 / 91 (5.49%)
         occurrences all number
    5
    3
    6
    Malaria
         subjects affected / exposed
    2 / 92 (2.17%)
    5 / 88 (5.68%)
    3 / 91 (3.30%)
         occurrences all number
    5
    8
    6
    Tonsillitis
         subjects affected / exposed
    3 / 92 (3.26%)
    5 / 88 (5.68%)
    8 / 91 (8.79%)
         occurrences all number
    5
    7
    10
    Upper respiratory tract infection
         subjects affected / exposed
    22 / 92 (23.91%)
    12 / 88 (13.64%)
    13 / 91 (14.29%)
         occurrences all number
    26
    13
    18
    Urinary tract infection
         subjects affected / exposed
    5 / 92 (5.43%)
    9 / 88 (10.23%)
    13 / 91 (14.29%)
         occurrences all number
    8
    10
    15
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    6 / 92 (6.52%)
    2 / 88 (2.27%)
    0 / 91 (0.00%)
         occurrences all number
    6
    2
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 92 (3.26%)
    2 / 88 (2.27%)
    5 / 91 (5.49%)
         occurrences all number
    3
    4
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Nov 2016
    Herein is a summary of the major changes made to the original protocol, dated 19 October 2016, and reflected in this Amendment 1, dated 09 November 2016: 1. Inclusion and Exclusion Criteria relevant to vaso-occlusive crisis (VOC) have been revised/clarified. 2. Certain laboratory tests results may suggest the treatment assignment; clarification has been made that these results may be redacted to the Investigator and monitored by the DSMB. 3. Study endpoints relevant to vaso-occlusive crisis (VOC) have been revised/clarified. 4. Additional instructions/clarifications have been included in the Schedule of Assessments.
    19 Jan 2017
    Herein is a summary of the major changes made to the Amendment 1 of this protocol, dated 09 November 2016 and reflected in this Amendment 2, dated 19 January 2017: 1. The duration of the study was clarified 2. The rationale for the placebo comparator arm was clarified 3. The unblinding language for medical need was revised to clarify that the investigator has authority to unblind for medical necessity
    18 Aug 2017
    Herein is a summary of the major changes made to the Amendment 2 of this protocol, dated 19 January 2017, and reflected in this Amendment 2.1, dated 18 August 2017: 1. Inclusion of Section Heading 1.1.1: Available Treatment for Patients with SCD: 2. Inclusion of Section 5.13: Imaging 3. Revision of Exclusion Criteria Number 8
    21 Sep 2017
    This protocol has been amended to address typos, provide updates regarding the development of GBT440, and to provide clarification and additional information/guidance. This amendment also includes changes to the design/operational aspects of the trial.
    03 Jan 2019
    This protocol has been amended to address changes to planned analyses, to provide updates regarding the development of voxelotor, and to provide clarification and additional information/guidance.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Group 3 was not enrolled, GBT submitted an NDA to US FDA under subpart H for voxelotor based on data collect from subjects in Groups 1 and 2 of this study.
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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