Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease

Purpose

This study consists of four parts, Parts A, B, C, and D. Part A is a single dose pharmacokinetic (PK) study in pediatric participants with Sickle Cell Disease. Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent Sickle Cell Disease participants who were 12-17 years of age. Part C is a multiple dose, safety, tolerability, and PK study, which includes the assessment of hematological effects and the effect on TCD flow velocity of voxelotor in pediatric participants with Sickle Cell Disease who are 4 to 17 years of age. Part D is a multiple dose, safety, tolerability, and PK study, which will examine the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease who are between 9 months to < 4 years of age.

Condition

  • Sickle Cell Disease

Eligibility

Eligible Ages
Between 9 Months and 17 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)
  2. Age:
  3. Part A - 6 to 17 years of age
  4. Part B - 12 to 17 years of age
  5. Part C - 4 to 17 years of age
  6. Part D - 9 months to <4 years of age
  7. Hydroxyurea (HU) therapy:
  8. Parts A, B, and C: A participant taking hydroxyurea (HU) may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustment during the study and no sign of hematological toxicity.
  9. Part D: A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose (MTD) is allowed during the study.
  10. Hemoglobin (HB):
  11. Part A - No restriction
  12. Parts B, C, & D - Hb ≤ 10.5 g/dL
  13. For Part C only: Participants 12 to 17 years of age must have a TCD velocity of ≥ 140 cm/sec measured anytime during screening.

Exclusion Criteria

  1. Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF):
  2. Vaso-occlusive crisis (VOC)
  3. Acute chest syndrome (ACS)
  4. Splenic sequestration crisis
  5. Dactylitis
  6. Requires chronic transfusion therapy
  7. History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements ≥ 200 cm/sec by non-imaging TCD or ≥185 cm/sec by TCDi).
  8. Transfusion within 30 days prior to signing the ICF

Exclusion Criteria for Part D Only:

16. Body weight <5 kg for 1 month prior to the screening visit and at the screening visit.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Voxelotor
Subjects to receive daily oral dosing of voxelotor according to which Part (A, B, C, or D), the subject is participating in: Part A: Subjects to receive daily oral dosing of voxelotor for 1 day (single dose) Part B: Subjects to receive daily oral dosing of voxelotor for up to 24 weeks (multiple dose) Part C: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose) Part D: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose)
  • Drug: Voxelotor
    Part A: Voxelotor will be administered as oral capsules or tablets Part B: Voxelotor will be administered as oral capsules or tablets Part C: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension Part D: Voxelotor will be administered as powder for oral suspension

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Imani Mojerie
202-476-3578
imojerie@childrensnational.org

More Details

NCT ID
NCT02850406
Status
Recruiting
Sponsor
Global Blood Therapeutics

Study Contact

Margaret Tonda, PharmD
(650) 741-7761
mtonda@gbt.com