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

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

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03036813
Acronym
GBT_HOPE
Enrollment
449
Registered
2017-01-30
Start date
2016-12-31
Completion date
2019-10-08
Last updated
2023-07-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sickle Cell Disease

Brief summary

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

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.

Interventions

DRUGvoxelotor
OTHERPlacebo

Sponsors

Pfizer
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Masking description

This study is a double-blind study.

Eligibility

Sex/Gender
ALL
Age
12 Years to 65 Years
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

Design outcomes

Primary

MeasureTime frameDescription
Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24Baseline to Week 24Number of participants with increase in Hb \>1 g/dL from Baseline to Week 24

Secondary

MeasureTime frameDescription
Annualized Vaso-Occlusive Crisis (VOC) Incidence RateBaseline to Week 72Number of Vaso-Occlusive Crisis (VOC) events averaged per year.
Percentage Change From Baseline in Hemolysis MeasuresBaseline to Week 24Percentage change from Baseline to week 24 in unconjugated bilirubin

Countries

Canada, Egypt, France, Italy, Jamaica, Kenya, Lebanon, Netherlands, Oman, Turkey (Türkiye), United Kingdom, United States

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 details

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

Participants by arm

ArmCount
Voxelotor 900mg
Participants received voxelotor 900 mg; administered orally, once daily for 72 weeks.
92
Voxelotor 1500mg
Participants received voxelotor 1500 mg; administered orally, once daily for 72 weeks
90
Placebo
Matching Placebo; administered orally, once daily for 72 weeks
92
Total274

Withdrawals & dropouts

PeriodReasonFG000FG001FG002
Overall StudyAdverse Event6116
Overall StudyLost to Follow-up110
Overall StudyNon-Compliance153
Overall StudyOther035
Overall StudyPhysician Decision211
Overall StudyPregnancy001
Overall StudyWithdrawal by Subject12610

Baseline characteristics

CharacteristicTotalVoxelotor 900mgVoxelotor 1500mgPlacebo
Age, Customized
12 to < 18
46 Participants15 Participants14 Participants17 Participants
Age, Customized
>=18 to < 65
228 Participants77 Participants76 Participants75 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
10 Participants4 Participants3 Participants3 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
253 Participants86 Participants82 Participants85 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
11 Participants2 Participants5 Participants4 Participants
Race/Ethnicity, Customized
Race
Arab/Middle Eastern
52 Participants19 Participants15 Participants18 Participants
Race/Ethnicity, Customized
Race
Asian
1 Participants0 Participants1 Participants0 Participants
Race/Ethnicity, Customized
Race
Black or African American
182 Participants60 Participants59 Participants63 Participants
Race/Ethnicity, Customized
Race
Missing/ Not Specified
2 Participants1 Participants1 Participants0 Participants
Race/Ethnicity, Customized
Race
Multiple
10 Participants2 Participants5 Participants3 Participants
Race/Ethnicity, Customized
Race
Other
11 Participants4 Participants2 Participants5 Participants
Race/Ethnicity, Customized
Race
White
16 Participants6 Participants7 Participants3 Participants
Region of Enrollment
Egypt
44 participants15 participants16 participants13 participants
Region of Enrollment
Europe
56 participants19 participants19 participants18 participants
Region of Enrollment
Jamaica
4 participants0 participants2 participants2 participants
Region of Enrollment
Kenya
49 participants17 participants14 participants18 participants
Region of Enrollment
Lebanon
7 participants3 participants3 participants1 participants
Region of Enrollment
North America
105 participants36 participants34 participants35 participants
Region of Enrollment
Oman
9 participants2 participants2 participants5 participants
Sex: Female, Male
Female
159 Participants51 Participants58 Participants50 Participants
Sex: Female, Male
Male
115 Participants41 Participants32 Participants42 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
2 / 922 / 882 / 91
other
Total, other adverse events
85 / 9285 / 8881 / 91
serious
Total, serious adverse events
20 / 9225 / 8823 / 91

Outcome results

Primary

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

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

Time frame: Baseline to Week 24

Population: All randomized subject (ITT population).

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Voxelotor 900 mgNumber of Participants With Increase in Hb >1 g/dL From Baseline to Week 2430 Participants
Voxelotor 1500 mgNumber of Participants With Increase in Hb >1 g/dL From Baseline to Week 2446 Participants
PlaceboNumber of Participants With Increase in Hb >1 g/dL From Baseline to Week 246 Participants
Secondary

Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate

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

Time frame: Baseline to Week 72

Population: Population excludes 3 subjects (1 in the placebo group and 2 in the voxelotor 1500-mg group) who were not treated.

ArmMeasureValue (MEAN)
Voxelotor 900 mgAnnualized Vaso-Occlusive Crisis (VOC) Incidence Rate2.4 Events per year
Voxelotor 1500 mgAnnualized Vaso-Occlusive Crisis (VOC) Incidence Rate2.4 Events per year
PlaceboAnnualized Vaso-Occlusive Crisis (VOC) Incidence Rate2.8 Events per year
Secondary

Percentage Change From Baseline in Hemolysis Measures

Percentage change from Baseline to week 24 in unconjugated bilirubin

Time frame: Baseline to Week 24

Population: Analysis population includes all randomized patients with a baseline value and at least one post-baseline value

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Voxelotor 900 mgPercentage Change From Baseline in Hemolysis Measures-20.1 percentage changeStandard Error 3.41
Voxelotor 1500 mgPercentage Change From Baseline in Hemolysis Measures-29.1 percentage changeStandard Error 3.46
PlaceboPercentage Change From Baseline in Hemolysis Measures-2.8 percentage changeStandard Error 3.51
Secondary

Percentage Change From Baseline in Hemolysis Measures

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

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Voxelotor 900 mgPercentage Change From Baseline in Hemolysis Measures4.7 percentage changeStandard Error 5.13
Voxelotor 1500 mgPercentage Change From Baseline in Hemolysis Measures-6.4 percentage changeStandard Error 5.17
PlaceboPercentage Change From Baseline in Hemolysis Measures4.7 percentage changeStandard Error 5.19
Secondary

Percentage Change From Baseline in Hemolysis Measures

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

Time frame: Baseline to Week 24

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Voxelotor 900 mgPercentage Change From Baseline in Hemolysis Measures-1.4 Percentage ChangeStandard Error 4.65
Voxelotor 1500 mgPercentage Change From Baseline in Hemolysis Measures-18.0 Percentage ChangeStandard Error 4.7
PlaceboPercentage Change From Baseline in Hemolysis Measures6.8 Percentage ChangeStandard Error 4.73
Secondary

Percentage Change From Baseline in Hemolysis Measures

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

Time frame: Baseline to Week 24

Population: Analysis population includes all randomized patients with a baseline value and at least one post-baseline value

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Voxelotor 900 mgPercentage Change From Baseline in Hemolysis Measures1.6 Percentage ChangeStandard Error 3.68
Voxelotor 1500 mgPercentage Change From Baseline in Hemolysis Measures-4.6 Percentage ChangeStandard Error 3.69
PlaceboPercentage Change From Baseline in Hemolysis Measures3.0 Percentage ChangeStandard Error 3.75

Source: ClinicalTrials.gov · Data processed: Feb 27, 2026