A Phase 2/3 Study of Osivelotor in Adult and Adolescent Participants With SCD

August 14, 2026 updated by: Pfizer

A PHASE 2/3 RANDOMIZED, MULTICENTER STUDY OF OSIVELOTOR ADMINISTERED ORALLY TO ADULT AND ADOLESCENT PARTICIPANTS WITH SICKLE CELL DISEASE

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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. (Complete) 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.

Study Type

Interventional

Enrollment (Estimated)

389

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
      • Rio de Janeiro, Brazil, 20211-030
        • Not yet recruiting
        • Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO
      • São Paulo, Brazil, 05403-000
        • Active, not recruiting
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      • São Paulo, Brazil, 05403-010
        • Active, not recruiting
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
      • São Paulo, Brazil, 01232-010
        • Not yet recruiting
        • Esho Empresa de Servicos Hospitalares S A
    • Pernambuco
      • Recife, Pernambuco, Brazil, 50070-460
        • Not yet recruiting
        • Multihemo Servicos Medicos S/A
    • SÃO Paulo- Brasil
      • São Paulo, SÃO Paulo- Brasil, Brazil, 01232-011
        • Not yet recruiting
        • Esho Empresa de Servicos Hospitalares S A
    • São Paulo
      • Ribeirão Preto, São Paulo, Brazil, 14051-140
        • Not yet recruiting
        • Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP
      • São, São Paulo, Brazil, 01228-000
        • Not yet recruiting
        • CPHosp Medicina, Ensino e Pesquisa Ltda
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Recruiting
        • Fundação Faculdade Regional de Medicina de São José do Rio Preto
      • São Paulo, São Paulo, Brazil, 08270-070
        • Not yet recruiting
        • Casa de Saude Santa Marcelina
      • São Paulo, São Paulo, Brazil, 08270-120
        • Not yet recruiting
        • Casa de Saude Santa Marcelina
      • São Paulo, São Paulo, Brazil, 01321 001
        • Not yet recruiting
        • BP A Beneficencia Portuguesa de Sao Paulo
      • São Paulo, São Paulo, Brazil, 01323-900
        • Not yet recruiting
        • BP - A Beneficência Portuguesa de São Paulo
  • India
    • Chhattisgarh
      • Raipur, Chhattisgarh, India, 492099
        • Not yet recruiting
        • AIIMS Raipur
    • Gujarat
      • Surat, Gujarat, India, 395002
        • Recruiting
        • Nirmal Hospital Pvt Ltd
      • Vadodara, Gujarat, India, 390020
        • Recruiting
        • Haemato Oncology Care Centre
    • Maharashtra
      • Nashik, Maharashtra, India, 422005
        • Recruiting
        • Chopda Medicare & Research Centre Pvt. Ltd: Magnum Heart Institute
    • National Capital Territory of Delhi
      • New Delhi, National Capital Territory of Delhi, India, 110029
        • Not yet recruiting
        • AIIMS Delhi
    • Odisha
      • Bhubaneswar, Odisha, India, 751019
        • Not yet recruiting
        • AIIMS, Bhubaneswar
  • Kenya
      • Nairobi, Kenya, 00100
        • Completed
        • Gertrude's Children's Hospital
      • Nairobi, Kenya, 00100
        • Completed
        • Kenya Medical Research Institute - Centre for Respiratory Disease Research
      • Nairobi, Kenya, 00200
        • Completed
        • Center for Research In Therapeutic Sciences (CREATES), Strathmore University Medical Centre
    • Siaya County
      • Kisumu, Siaya County, Kenya, 40600
        • Completed
        • KEMRI/CRDR, Siaya, KEMRI Clinical Research Annex
  • Nigeria
      • Kano, Nigeria, 700233
        • Completed
        • Aminu Kano Teaching Hospital
      • Lagos, Nigeria, 100254
        • Completed
        • Lagos University Teaching Hospital
    • Oyo/ibadan North
      • Ibadan, Oyo/ibadan North, Nigeria, 200212
        • Completed
        • University College Hospital Ibadan
  • Saudi Arabia
    • Riyadh Region
      • Riyadh, Riyadh Region, Saudi Arabia, 11472
        • Not yet recruiting
        • King Khalid University Hospital
  • United Kingdom
      • Bristol, United Kingdom, BS2 8ED
        • Recruiting
        • University Hospitals Bristol and Weston NHS Foundation Trust
      • Bristol, United Kingdom, BS2 8EX
        • Recruiting
        • Bristol Royal Infirmary
      • London, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital NHS Foundation Trust
      • London, United Kingdom, W12 0HS
        • Recruiting
        • Hammersmith Hospital
      • London, United Kingdom, W12 0HS
        • Recruiting
        • Hammersmith Hospital, Imperial College Healthcare NHS Trust
      • London, United Kingdom, NW1 2PG
        • Recruiting
        • University College London Hospital
      • London, United Kingdom, SE1 9RT
        • Recruiting
        • Guy's & St Thomas' NHS Foundation Trust
  • United States
    • Alabama
      • Mobile, Alabama, United States, 36608
        • Recruiting
        • AMR Clinical
    • Connecticut
      • Hartford, Connecticut, United States, 06106
        • Not yet recruiting
        • Connecticut Children's Medical Center
      • New Haven, Connecticut, United States, 06511
        • Not yet recruiting
        • Smilow Cancer Hospital
    • Florida
      • Plantation, Florida, United States, 33317
        • Recruiting
        • Edward Jenner Research Group LLC.
      • West Palm Beach, Florida, United States, 33407
        • Recruiting
        • St. Mary's Medical Center
      • West Palm Beach, Florida, United States, 33407
        • Recruiting
        • Pediatric Hematology / Oncology a division of Kidz Medical services
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Recruiting
        • Children's Center for Advanced Pediatrics
      • Dunwoody, Georgia, United States, 30350
        • Active, not recruiting
        • Alpha Clinical Research Georgia
      • Riverdale, Georgia, United States, 30274
        • Active, not recruiting
        • Sonar Clinical Research
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois Hospital and Health Sciences System
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois at Chicago Clinical Research Center
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • University of Illinois Hospital and Health Sciences System - Investigational Drug Services (IDS)
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70805
        • Active, not recruiting
        • LSU Health Baton Rouge-North Clinic
      • Baton Rouge, Louisiana, United States, 70808
        • Active, not recruiting
        • Our Lady of the Lake Hospital, Inc.
      • Baton Rouge, Louisiana, United States, 70808
        • Active, not recruiting
        • Our Lady of the Lake Hospital
      • New Orleans, Louisiana, United States, 70112
        • Active, not recruiting
        • University Medical Center New Orleans
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Not yet recruiting
        • Children's Hospital of Michigan
      • Southfield, Michigan, United States, 48075
        • Not yet recruiting
        • Great Lakes Research Institute, Flourish Detroit
    • Mississippi
      • Flowood, Mississippi, United States, 39232
        • Recruiting
        • Southern Specialty Research
      • Madison, Mississippi, United States, 39110
        • Active, not recruiting
        • Mississippi Center for Advanced Medicine
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • University Health
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Robert Wood Johnson University Hospital
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Jack & Sheryl Morris Cancer Center
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai
      • The Bronx, New York, United States, 10461
        • Recruiting
        • Jacobi Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • Not yet recruiting
        • UNC Health
      • Chapel Hill, North Carolina, United States, 27514
        • Not yet recruiting
        • Clinical & Translational Research Center (CTRC)
      • Chapel Hill, North Carolina, United States, 27517
        • Not yet recruiting
        • UNC Eastowne Medical Office Building - Consent Only
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University IDS Pharmacy
      • Greenville, North Carolina, United States, 27834
        • Recruiting
        • ECU Physicians, Brody Outpatient Clinic
      • Morrisville, North Carolina, United States, 27560
        • Not yet recruiting
        • UNC IDS
    • South Carolina
      • Clinton, South Carolina, United States, 29325
        • Recruiting
        • Prisma Health Laurens County Hospital
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Greenville Memorial Hospital
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health - Upstate
      • Greenville, South Carolina, United States, 29615
        • Recruiting
        • Prisma Health Patewood Hospital
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Outpatient Radiology - Greenville
      • Greer, South Carolina, United States, 29650
        • Recruiting
        • Prisma Health Greer Memorial Hospital
      • Simpsonville, South Carolina, United States, 29681
        • Recruiting
        • Prisma Health Hillcrest Hospital
      • Travelers Rest, South Carolina, United States, 29690
        • Recruiting
        • Prisma Health North Greenville Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • The University of Texas Health Science Center at Houston
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • McGovern Medical School at UTHealth
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • Memorial Hermann Hospital, Texas Medical Center - Clinical Research Unit (CRU)
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • UT Physicians Comprehensive Sickle Cell Clinic
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Part A and Part B:

  • Male or female with SCD, HbSS and HbSB-zero
  • Participants with Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL during Screening and considered stable 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 years and older, inclusive at screening.
  • Participants with more than or equal to 2 and ≤ 10 VOCs within 12 months of Screening.

OLE:

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

Exclusion Criteria:

Part A and Part B:

  • 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.
  • Participants in Sub-Saharan Africa or who have relocated from Sub-Saharan Africa within 6 months.

OLE:

  • Have any unresolved clinically significant adverse event, laboratory abnormality, or safety finding from Part B that, in the opinion of the Investigator, increases the risk of study drug administration.
  • Met permanent treatment discontinuation criteria during Part B.
  • Have withdrawn consent or are unable to comply with study procedure

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Part A

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.
Drug: Osivelotor
Tablets which contain drug substance
Other Names:
  • PF-07940367 or GBT021601
Placebo Comparator: Part B

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.
Drug: Osivelotor
Tablets which contain drug substance
Other Names:
  • PF-07940367 or GBT021601
Experimental: OLE

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.
Drug: Osivelotor
Tablets which contain drug substance
Other Names:
  • PF-07940367 or GBT021601

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Part A
Time Frame: Through week 12
Number of adult participants with change from baseline in hemoglobin (Hb) through week 12 as measured by change in osivelotor concentrations from baseline or percentage change from baseline of clinical measures of anemia Hb and hemolysis (including indirect bilirubin, reticulocytes and lactate dehydrogenase).
Through week 12
Part B
Time Frame: Through week 48

Co-primary endpoints: Hb response (increase from baseline of >1 g/dL) at Week 48 (based on average of Hb levels at Week 40 and Week 48) and the Annualized rate of VOC through end of Week 48.

A VOC is defined as an acute episode of pain that:

  • Has no medically determined cause other than a vaso-occlusive event, and
  • Results in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), and
  • Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics.

Complicated VOCs of acute chest syndrome (ACS), hepatic sequestration, splenic sequestration, priapism, and dactylitis that meet the requirements listed above will be included in this co-primary endpoint.
Through week 48
OLE
Time Frame: Approximately 24 months after last patient enrolled

Incidence of Treatment Emergent Adverse Events:

  • Incidence of SAEs
  • Incidence of AEs leading to discontinuation
  • Change from baseline in laboratory parameters.
Approximately 24 months after last patient enrolled

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pfizer

Collaborators

Pfizer

Investigators

  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 22, 2022

Primary Completion (Estimated)

December 30, 2030

Study Completion (Estimated)

December 31, 2032

Study Registration Dates

First Submitted

June 21, 2022

First Submitted That Met QC Criteria

June 21, 2022

First Posted (Actual)

June 24, 2022

Study Record Updates

Last Update Posted (Actual)

August 18, 2026

Last Update Submitted That Met QC Criteria

August 14, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GBT021601-021
  • C5351004 (Other Identifier: Alias Study Number)
  • 2023-508766-14-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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