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

• Register: EUCTR
• Last refreshed on: 7 September 2020
• Main ID: EUCTR2016-003370-40-NL
• Date of registration: 28/03/2017
• Prospective Registration: Yes
• Primary sponsor: Global Blood Therapeutics, Inc.
• Public title: A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease
• Scientific title: A Phase 3, Double-blind, Randomized, Placebo-controlled, Multicenter Study of Voxelotor Administered Orally to Patients With Sickle Cell Disease
• Date of first enrolment: 31/08/2017
• Target sample size: 370
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003370-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Egypt, France, Germany, Ghana, Italy, Jamaica, Kenya, Lebanon, Netherlands, Nigeria, Oman, Turkey, United Kingdom, United States

Contacts

• Name: Sr. Clinical Trial Manager
• Affiliation: Global Blood Therapeutics, Inc.

• Name: Sr. Clinical Trial Manager
• Affiliation: Global Blood Therapeutics, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
All participants must meet the following inclusion criteria:
1. Male or female study participants with Sickle Cell Disease:
• Documentation of SCD genotype (HbSS, HbSC, HbSß thalassemia or other sickle cell syndrome variants) may be based on history of laboratory testing or must be confirmed by
laboratory testing during screening
2. Participants have had at least 1 episode of VOC in the past 12 months. For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)
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 90 days prior to signing the ICF and with no anticipated need for dose adjustments or initiation during the study, in the opinion of the Investigator
6. Participants must demonstrate 75% compliance with ePRO measure completion to be randomised (participants will be given an ePRO device for at least 28 days during Screening; participants who have <75% compliance may be rescreened up to two times for PRO compliance.
7. Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 30 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 3 months after the last dose of study drug
8. Participant has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant’s legal representative or legal guardian, and the participant’s assent must be obtained)
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 320
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Any participant who meets one or more of the following criteria will be excluded from participation:
1. More than 10 VOCs within the past 12 months that required a hospital, or emergency room or clinic visit
2. Female who is breast feeding or pregnant
3. 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 or at any time during the screening period.
4. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days prior to signing the ICF
(i.e., a vaso-occlusive event cannot be within 14 days prior to ICF)
5. Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN
6. Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:
• Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
• Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
7. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory) <30mL/min/1.732 or on chronic dialysis
8. History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)
9. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
• Unstable angina pectoris or myocardial infarction or elective coronary intervention
• Congestive heart failure requiring hospitalization
• Uncontrolled clinically significant arrhythmias
10. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)
11. Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device)
12. Inadequate venous access as determined by the Investigator/site staff
13. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent
14. Receipt of erythropoietin or other hematopoietic growth factors within 28 days of signing ICF or anticipated need for such agents during the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Sickle Cell Disease
MedDRA version: 21.0 Level: PT Classification code 10040644 Term: Sickle cell disease System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: GBT440 300 mg capsule
Product Code: GBT440
Pharmaceutical Form: Capsule
Current Sponsor code: GBT440
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: GBT440 300 mg Tablets
Product Code: GBT440
Pharmaceutical Form: Tablet
Current Sponsor code: GBT440
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: The primary objective is to assess the efficacy of GBT440 in adolescents and adults with Sickle Cell Disease (SCD) as measured by improvement in anemia.

Primary end point(s): The primary efficacy measure is Hb response., defined as increase of Hb from baseline by > 1 g/dL at 24 weeks. Hb at 24 weeks is determined by the average value of Hb levels at Week 20 and Week 24.

Secondary Objective: The secondary objectives are to evaluate the effects of GBT440 compared to placebo on SCD symptom exacerbation and TSS from PRO measurement, measures of anemia and hemolysis, and other clinical measures (e.g., VOC, ACS, hospitalization, RBC transfusions, opioid use).

Timepoint(s) of evaluation of this end point: Day 1, Weeks 2,4,6,8,12,16,20,24,36,48,60,72, EOS(+4weeks)

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoints are as follows:
· Change from baseline in hemoglobin at Week 24
· Change and percent change from baseline in hemolysis measures, including unconjugated bilirubin, absolute reticulocyte, reticulocytes %, and LDH at Week 24
· Incidence of severe anemic episodes (Hb < 5.5 g/dL)
· Annualized incidence rate of VOC

Timepoint(s) of evaluation of this end point: Day 1, Weeks 2,4,6,8,12,16,20,24,36,48,60,72, EOS(+4weeks)

Secondary ID(s)

2016-003370-40-GB

GBT440-031

Source(s) of Monetary Support

Global Blood Therapeutics, Inc.

Ethics review

Status: Approved
Approval date: 31/08/2017
Contact: