Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease (HOPE-KIDS)

Pfizer

Status and phase: Terminated; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: Voxelotor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02850406

C5341020 (Other Identifier)

GBT440-007

Details and patient eligibility

About

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.

Enrollment: 147 patients

Sex: All

Ages: 6 months to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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147 participants in 1 patient group

Voxelotor

Experimental group

Description:

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 equivalent dose)

Treatment:

Drug: Voxelotor