A Phase 3, Randomized, Double-Blind, Placebo Controlled Study of Voxelotor (GBT440) in Pediatric Participants with Sickle Cell Disease and an Open-label Study in Infants with Sickle Cell Disease (HOPE Kids 2)

Phase 1

• Conditions: Sickle Cell Disease; MedDRA version: 20.0 Level: LLT Classification code 10040644 Term: Sickle cell disease System Organ Class: 100000004850; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2017-000903-26-GB
• Lead Sponsor: Global Blood Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-06-22
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 140

Inclusion Criteria

PART A:
1.Age 2 to < 12 years at the time of informed caregiver/legal guardian consent. ·
2.Male or female study participants with SCD. Documentation of SCD genotype (HbSS, HbSC, HbSß0thal. or other sickle cell syndrome variants) is required and may be based on prior history of laboratory testing or must be confirmed by laboratory testing during screening.
3.Participants must have had at least 1 episode of VOC in the past 12 months. VOC is defined as a previously documented episode of acute painful crisis (for which there was no explanation other than VOC) or Acute Chest Syndrome (ACS) which required prescription or healthcare professional instructed use of analgesics for moderate to severe pain (documentation must exist in the participant’s medical record prior to Screening).
4.For participants taking HU, the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the informed consent form (ICF) and/or assent form, and with no anticipated need for dose adjustments or initiation during the study, in the opinion of the Investigator.
5.Hb = 5.5 g/dL =10.5 g/dL.
6.Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.
7.Adequate venous access to permit monitoring of laboratory safety variables and collection of PK samples, in the opinion of the Investigator.
8.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 30 days after the last dose of study drug.
9.Females of child-bearing potential are required to have a negative pregnancy test before randomization.

PART B:
Participants who meet all of the following criteria will be eligible for study enrollment in Part B:
1.Age =9 months to <24 months of age at the time of informed caregiver/legal guardian consent. ·
2.Male or female study participants with sickle cell disease. Documentation of SCD genotype (HbSS, HbSC, HbSß thalassemia or other sickle cell syndrome variants) is required and may be based on history of laboratory testing or must be confirmed by laboratory testing duringthe Screening Period.
3. Adequate venous access to permit monitoring of laboratory safety variables and collection of PK samples, in the opinion of the Investigator.
4.. A written informed parental/legal guardian consent has been obtained per institutional review board (IRB)/Ethics Committee (EC) policy and requirements, consistent with ICH guidelines

Are the trial subjects under 18? yes
Number of subjects for this age range: 140
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

PART A and PART B:
1.Body weight < 5kg at the screening visit.
2.VOC:
•Hospitalization for VOC within the 28 days prior to execution of informed consent/assent.
•A VOC in the screening period requiring hospitalization, hospital emergency room visit or a clinic visit resulting in a new prescription of analgesics is an exclusion.
•A VOC that does not require hospitalization during the screening period is not an exclusion provided that the hemoglobin level prior to randomization is within 1 g/dL of the screening value.
•More than 10 VOCs within the past 12 months that required hospitalization, or Emergency Room or clinic visit.
3.Severe renal dysfunction (<60 mL/min/1.73 m2 by Schwartz formula).
4.Hepatic dysfunction characterized by ALT > 4x ULN for age.
5.Clinically relevant cardiac abnormality, in the opinion of the Investigator, such as: ·
•Hemodynamically significant heart disease, eg congenital heart disease with left to right shunt or cyanosis, congestive heart failure, or an unstable cardiac condition. ·
•An arrhythmic heart condition requiring medical therapy. ·
•History of clinically significant abnormal electrocardiogram (ECG), congenital long QT syndrome, second or third-degree heart block at rest (except for asymptomatic Mobitz type I second degree heart block).
6.Participants with clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy:
•Participants with acute bacterial infection requiring antibiotic use should delay screening 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.
•Participants who have tested positive for malaria at screening.
•Participants with acute malaria infection should delay screening until infection has been resolved and their hemoglobin level has, in the opinion of the Investigator, returned to the participant’s pre-infection level.
7.Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).
8.Received an investigational drug within 30 days or 5 half-lives, whichever is longer, of the parent/legal guardian signing the ICF.
9.Parent or legal guardian/participants are unlikely to comply with the study procedures.
10.Other medical, psychological or addictive condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety, efficacy and/or PK of the investigational drug, prevent compliance with the study protocol, or preclude informed consent.

Additionally, for PART A only:
1.Meets the criteria for primary stroke prophylaxis.
2.Has been treated with erythropoietin or other hematopoietic growth factors within 28 days of signing informed consent/assent or if, in the opinion of the Investigator, there is an anticipated need for such agents during the study.
3.RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion) or has received a RBC transfusion or exch

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified