Sickle Cell Disease
Conditions
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. (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.
Interventions
DRUGOsivelotor
Tablets which contain drug substance
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Part B only
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| OLE | 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. |
Countries
Brazil, India, Kenya, Nigeria, Saudi Arabia, United Kingdom, United States
Contacts
CONTACTPfizer Pfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed