A Phase 2/3 Study in Adult and Adolescent 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.

Open Label Extension (OLE) will evaluate the long-term safety and hematologic responses of open-label osivelotor in adult and adolescent participants having completed Part B.

Enrollment: 389 estimated patients

Sex: All

Ages: 12 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Part A, Part B, and OLE:

• 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.

OLE:

- Participants who have completed the Part B will be eligible.

Exclusion criteria

Part A, Part B, and OLE:

• 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 or anytime during the screening period.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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389 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:

Study drug arm: Adult participants will receive osivelotor at 300 mg QD loading dose for 7 days followed by 150 mg QD through Week 48. Adolescent participant dose will be defined in a future protocol amendment. Placebo arm: Participants will receive placebo tablets for 48 weeks.

Treatment:

Drug: Osivelotor

OLE

Experimental group

Description:

Adult Participants will receive 150 mg open-label osivelotor up to 2 years after the last participant's visit in Part B or when the drug is commercially available in that region. The appropriate doses for adolescents will be defined in a future protocol amendment.

Treatment:

Drug: Osivelotor