Clinical trial NCT03036813: Study to Evaluate the Effect of Voxelotor Administered Orally to Patients With Sickle Cell Disease (GBT_HOPE)
Official title: A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Sickle Cell Disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2017-01-30
Enrollment: 449
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Increase in Hb >1 g/dL From Baseline to Week 24
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate
timeFrame: Baseline to Week 72
measure: Percentage Change From Baseline in Hemolysis Measures
timeFrame: Baseline to Week 24
measure: Percentage Change From Baseline in Hemolysis Measures
timeFrame: Baseline to Week 24
measure: Percentage Change From Baseline in Hemolysis Measures
timeFrame: Baseline to Week 24
measure: Percentage Change From Baseline in Hemolysis Measures
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Little Rock
country: United States
state: Arkansas
city: Oakland
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Baton Rouge
country: United States
state: Louisiana
city: New Orleans
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Bethesda
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Newark
country: United States
state: New Jersey
city: Bronx
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Oklahoma City
country: United States
state: Oklahoma
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Toronto
country: Canada
city: Alexandria
country: Egypt
city: Cairo
country: Egypt
city: Cairo
country: Egypt
city: Zagazig
country: Egypt
city: Créteil
country: France
city: Paris
country: France
city: Paris
country: France
city: Monza
country: Italy
state: Milano
city: Padova
country: Italy
city: Verona
country: Italy
city: Kingston
country: Jamaica
city: Nairobi
country: Kenya
city: Nairobi
country: Kenya
city: Nairobi
country: Kenya
city: Siaya
country: Kenya
city: Beirut
country: Lebanon
city: Beirut
country: Lebanon
city: Tripoli
country: Lebanon
city: Amsterdam
country: Netherlands
city: Den Haag
country: Netherlands
city: Rotterdam
country: Netherlands
city: Muscat
country: Oman
city: Adana
country: Turkey
city: Kayseri
country: Turkey
city: Mersin
country: Turkey
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 May;8(5):e323-e333. doi: 10.1016/S2352-3026(21)00059-4. Epub 2021 Apr 7.
citation: Minniti CP, Knight-Madden J, Tonda M, Gray S, Lehrer-Graiwer J, Biemond BJ. The impact of voxelotor treatment on leg ulcers in patients with sickle cell disease. Am J Hematol. 2021 Apr 1;96(4):E126-E128. doi: 10.1002/ajh.26101. Epub 2021 Feb 19. No abstract available.
citation: Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. doi: 10.1056/NEJMoa1903212. Epub 2019 Jun 14.
citation: Metcalf B, Chuang C, Dufu K, Patel MP, Silva-Garcia A, Johnson C, Lu Q, Partridge JR, Patskovska L, Patskovsky Y, Almo SC, Jacobson MP, Hua L, Xu Q, Gwaltney SL 2nd, Yee C, Harris J, Morgan BP, James J, Xu D, Hutchaleelaha A, Paulvannan K, Oksenberg D, Li Z. Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin. ACS Med Chem Lett. 2017 Jan 23;8(3):321-326. doi: 10.1021/acsmedchemlett.6b00491. eCollection 2017 Mar 9.