A Phase 2/3 Study in Adult and Pediatric Participants With SCD

Pfizer

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Sickle Cell Disease

Treatments: Drug: Osivelotor

Study type: Interventional

Funder types: Industry

Identifiers

NCT05431088

2023-508766-14-00 (Registry Identifier)

C5351004 (Other Identifier)

GBT021601-021

Details and patient eligibility

About

The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of osivelotor.

Full description

This is a three-part, multicenter, Phase 2/3 study of orally administered osivelotor in participants with sickle cell disease (SCD).

Part A will evaluate the safety, tolerability, and efficacy of osivelotor in adult participants with SCD to determine an optimal dose.

Part B will evaluate the efficacy of osivelotor versus placebo in adult and adolescent participants with SCD for 48 weeks.

Part C will evaluate the pharmacokinetics (PK) and safety of single and multiple doses (MD) of open-label single arm osivelotor administered to pediatric participants.

Enrollment: 517 estimated patients

Sex: All

Ages: 6 months to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Part A, Part B, and Part C:

• Male or female with SCD
• Participants with stable Hb value as judged by the Investigator
• For participants taking hydroxyurea and/or L-glutamine, the dose must be stable for at least 90 days prior to signing the ICF or assent and with no anticipated need for dose adjustments during the study in the opinion of the Investigator.

Part B:

• Participants with SCD ages 12 to 65 years, inclusive
• Participants with more than or equal to 2 and ≤ 10 VOCs within 12 months of Screening.

Exclusion criteria

Part A, Part B, and Part C:

• Participants who had more than 10 VOC within 12 months of screening
• Female participant who is breastfeeding or pregnant
• Participants who receive RBC transfusion therapy regularly or received an RBC transfusion ---for any reason within 90 days of Day 1
• Participants hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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517 participants in 3 patient groups, including a placebo group

Part A

Active Comparator group

Description:

Initially, participants will be randomized 1:1 to 100 mg and 150 mg daily. Upon review of the 150 mg safety data from at least 6 participants, there will be 1:1:1 randomization: 100 mg, 150 mg, and up to 200 mg. Participants will then receive maintenance once daily doses through Week 12.

Treatment:

Drug: Osivelotor

Part B

Placebo Comparator group

Description:

Following the selection of the optimal safe and effective dose from Part A of the study, Part B of the study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo

Treatment:

Drug: Osivelotor

Part C

Experimental group

Description:

100 mg dose in cohort C1, dose level for cohorts C2 to C4 to be determined based on emerging data

Treatment:

Drug: Osivelotor