A Phase 2/3 Study in Adult and Pediatric Participants With SCD
- Registration Number
- NCT05431088
- Lead Sponsor
- Pfizer
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of osivelotor.
- 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.
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 429
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.
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part C Osivelotor 100 mg dose in cohort C1, dose level for cohorts C2 to C4 to be determined based on emerging data Part A Osivelotor 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. Part B Osivelotor 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
- Primary Outcome Measures
Name Time Method Part A 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).
Part B 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.Part C Through Week 2 Assess the PK AUC0-last, AUC0-inf, and Cmax after single dose of osivelotor in whole blood and plasma.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (47)
LSU Health Baton Rouge-North Clinic
🇺🇸Baton Rouge, Louisiana, United States
Our Lady of the Lake Hopistal, Inc
🇺🇸Baton Rouge, Louisiana, United States
Our lady of the Lake Hospital
🇺🇸Baton Rouge, Louisiana, United States
KEMRI/CRDR, Siaya, KEMRI Clinical Research Annex
🇰🇪Kisumu, Siaya, Kenya
Gertrude's Children's Hospital
🇰🇪Nairobi, Kenya
Center for Research In Therapeutic Sciences (CREATES), Strathmore University Medical Centre
🇰🇪Nairobi, Kenya
Kenya Medical Research Institute - Centre for Respiratory Disease Research
🇰🇪Nairobi, Kenya
University College Hospital Ibadan
🇳🇬Ibadan, Oyo/ibadan North, Nigeria
Lagos University Teaching Hospital
🇳🇬Lagos, Nigeria
Aminu Kano Teaching Hospital
🇳🇬Kano, Nigeria
Memorial Hermann Hospital, Texas Medical Center - Clinical Research Unit (CRU)
🇺🇸Houston, Texas, United States
Truman Medical Center
🇺🇸Kansas City, Missouri, United States
Lundquist Institute for Biomedical Innovation at Harbor- UCLA Medical Center
🇺🇸Torrance, California, United States
Lynn Institute of the Ozarks
🇺🇸Little Rock, Arkansas, United States
Smilow Cancer Center at Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
Children's National Health System
🇺🇸Washington, District of Columbia, United States
Children's National Hospital
🇺🇸Washington, District of Columbia, United States
Edward Jenner Research Group LLC.
🇺🇸Miami, Florida, United States
Kidz Hematology / Oncology a division of Kidz Medical
🇺🇸West Palm Beach, Florida, United States
Palm Beach Children's Hospital at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
Sonar Clinical Research
🇺🇸Atlanta, Georgia, United States
Alpha Clinical Research Georgia
🇺🇸Dunwoody, Georgia, United States
University of Illinois Hospital and Health Sciences System - Hospital Pharmacy Services
🇺🇸Chicago, Illinois, United States
University of Illinois Hospital and Health Sciences System
🇺🇸Chicago, Illinois, United States
University of Illinois at Chicago Clinical Research Center
🇺🇸Chicago, Illinois, United States
University of Illinois Hospital and Health Sciences System - Investigational Drug Services (IDS)
🇺🇸Chicago, Illinois, United States
Our Lady of the Lake Physicians Group, Medical Oncology
🇺🇸Baton Rouge, Louisiana, United States
Our Lady of the Lake Hospital, Inc In-Patient Pharmacy
🇺🇸Baton Rouge, Louisiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Mississippi Center for Advanced Medicine
🇺🇸Madison, Mississippi, United States
UNC Hospitals, The University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
UT Physicians Comprehensive Sickle Cell Clinic
🇺🇸Houston, Texas, United States
McGovern Medical School/Health Science Center Houston
🇺🇸Houston, Texas, United States
Memorial Hermann - TMC Investigational Drugs, IDS Pharmacy
🇺🇸Houston, Texas, United States
Inova Schar Cancer Institute Infusion Pharmacy
🇺🇸Fairfax, Virginia, United States
Inova Schar Cancer Institute
🇺🇸Fairfax, Virginia, United States
Clinical Research Services Unit - Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
🇧🇷São Paulo, Brazil
Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP
🇧🇷Ribeirão Preto, SÃO Paulo, Brazil
Instituto Estadual de Hematologia Arthur Siqueira Cavalcanti - HEMORIO
🇧🇷Rio de Janeiro, Brazil
HEMORIO - Unidade de Pesquisa Clínica
🇧🇷Rio De Janeiro, Brazil
Real e Benemerita Associacao Portuguesa de Sao Paulo
🇧🇷Sao Paulo, Brazil
Nirmal Hospital Pvt Ltd
🇮🇳Surat, Gujarat, India
Chopda Medicare & Research Centre Pvt. Ltd: Magnum Heart Institute
🇮🇳Nashik, Maharashtra, India
University Hospitals Bristol and Weston NHS Foundation Trust
🇬🇧Bristol, United Kingdom
Bristol Royal Infirmary
🇬🇧Bristol, United Kingdom