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

Open to people ages 6 months to 17 years

• 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.

• 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.