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

A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease

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 ages 6 to 17 years.
• Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent participants with Sickle Cell Disease ages 12 to 17 years.
• 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 ages 4 to 17 years.
• Part D is a multiple dose, safety, tolerability, and PK study, which examines the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease ages 6 months to < 4 years.

Inclusion Criteria:

• Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)

• Age:

  • Part A - 6 to 17 years of age
  • Part B - 12 to 17 years of age
  • Part C - 4 to 17 years of age
  • Part D - 6 months to <4 years of age

• Hydroxyurea (HU) therapy:

  • 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.
  • 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.

• Hemoglobin (HB):

  • Part A - No restriction
  • Parts B, C, & D - Hb ≤ 10.5 g/dL

• 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:

• Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF):

  • Vaso-occlusive crisis (VOC)
  • Acute chest syndrome (ACS)
  • Splenic sequestration crisis
  • Dactylitis

• Requires chronic transfusion therapy

• 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).

• Transfusion within 30 days prior to signing the ICF

Exclusion Criteria for Part D Only:

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