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

• ClinicalTrials.gov Identifier: NCT03036813
• Recruitment Status: Completed
• First Posted: January 30, 2017
• Results First Posted: January 7, 2021
• Last Update Posted: January 7, 2021
• Sponsor: Global Blood Therapeutics
• Information provided by (Responsible Party): Global Blood Therapeutics

Tracking Information

• First Submitted Date: January 27, 2017
• First Posted Date: January 30, 2017
• Results First Submitted Date: October 28, 2020
• Results First Posted Date: January 7, 2021
• Last Update Posted Date: January 7, 2021
• Actual Study Start Date: December 2016
• Actual Primary Completion Date: October 8, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 5, 2021)

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

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

Original Primary Outcome Measures (submitted: January 27, 2017)

Change in hemoglobin (Hb) [ Time Frame: Baseline to Week 24 ]

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

Current Secondary Outcome Measures (submitted: January 5, 2021)

• Annualized Vaso-Occlusive Crisis (VOC) Incidence Rate [ Time Frame: Baseline to Week 72 ]
  Number of Vaso-Occlusive Crisis (VOC) events averaged per year.
• Percentage Change From Baseline in Hemolysis Measures [ Time Frame: Baseline to Week 24 ]
  Percentage change from Baseline to week 24 in unconjugated bilirubin
• Percentage Change From Baseline in Hemolysis Measures [ Time Frame: 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.
• Percentage Change From Baseline in Hemolysis Measures [ Time Frame: Baseline to Week 24 ]
  Percentage change from Baseline to week 24 in reticulocytes % which is a % of total Red Blood Cells (RBCs).
• Percentage Change From Baseline in Hemolysis Measures [ Time Frame: Baseline to Week 24 ]
  Percentage change from Baseline to week 24 in Lactate Dehydrogenase (LDH)

Original Secondary Outcome Measures (submitted: January 27, 2017)

• Proportion of days with SCD symptom exacerbation [ Time Frame: Baseline to Week 24 ]
  Calculated from Sickle Cell Disease Severity Measure (SCDSM)
• Change in the SCDSM Total Symptom Score [ Time Frame: Baseline to Week 24 ]
  Calculated from SCDSM

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:

This study is a double-blind study.

Primary Purpose: Treatment

• Condition: Sickle Cell Disease

Intervention

• Drug: voxelotor
  Other Name: GBT440
• Other: Placebo

Study Arms

• Active Comparator: Dose 1
  voxelotor
  Intervention: Drug: voxelotor
• Active Comparator: Dose 2
  voxelotor
  Intervention: Drug: voxelotor
• Placebo Comparator: Placebo
  Placebo
  Intervention: Other: Placebo

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 17, 2019): 449
• Original Estimated Enrollment (submitted: January 27, 2017): 400
• Actual Study Completion Date: October 8, 2019
• Actual Primary Completion Date: October 8, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Egypt, France, Italy, Jamaica, Kenya, Lebanon, Netherlands, Oman, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT03036813
• Other Study ID Numbers: GBT440-031
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Global Blood Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Global Blood Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Global Blood Therapeutics
• Verification Date: January 2021