Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease
Study Details
Study Description
Brief Summary
Etavopivat (FT-4202) is a potent, selective, orally bioavailable, small-molecule activator of erythrocyte pyruvate kinase (PKR) being developed by Forma Therapeutics, Inc. and is intended for use as a treatment for participants with sickle cell disease (SCD) and other inherited hemoglobinopathies. The clinical hypothesis is that PKR activation will reduce sickle hemoglobin (HbS) polymerization and improve red blood cell (RBC) membrane function, thereby reducing RBC sickling and RBC hemolysis that leads to vascular obstruction and anemia, two hallmarks of SCD pathology. The aim of this study is to determine the effects of etavopivat on cerebral and muscle hemodynamics
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This study is a pilot, open-label, single-arm study to evaluate the effect of etavopivat on cerebral hemodynamics, as measured by frequency domain near-infrared spectroscopy/diffuse correlation spectroscopy (FDNIRS/DCS) in participants 12 to 21 years of age with sickle cell disease (SCD). Cerebral blood flow (CBF), oxygen ejection fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) will be assessed FDNIRS/DCS in participants prior to, periodically throughout, and after 24 weeks of treatment with etavopivat. Approximately 12 participants will be enrolled.
The duration of study treatment will be 24 weeks. The study duration for individual participants may last up to 36 to 38 weeks and includes the Screening Period (up to 4 weeks before study treatment), the 24-week treatment period, a Safety Follow-up Visit at 4 weeks (+ 7 days) after the last dose of study drug, and an End of Study (EOS) visit approximately 8 weeks (± 7 days) after the last dose of study drug. A participant is considered to have completed the study if he or she has completed all phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Events. Periodic safety reviews via the sponsor's internal Safety Review Committee (SRC), will occur throughout the treatment period. The outcome of these meetings, when relevant, will be quickly communicated to study Investigators so they may share current risk information with their participants and collect updated informed consent forms, if appropriate.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Etavopivat Single-arm, open-label |
Drug: Etavopivat
The study intervention is etavopivat (400 mg), administered orally and once daily (QD)
Other Names:
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Outcome Measures
Primary Outcome Measures
- Effect of etavopivat on cerebral blood flow (CBF) [24 weeks]
Change in cerebral blood flow (CBF) assessments from baseline will be summarized with descriptive statistics by nominal study visit.
- Effect of etavopivat on oxygen ejection fraction (OEF) [24 weeks]
Change in OEF assessments from baseline will be summarized with descriptive statistics by nominal study visit.
- Effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2) [24 weeks]
Change in CMRO2 assessments from baseline will be summarized with descriptive statistics by nominal study visit.
Secondary Outcome Measures
- Relationship between CBF and change in Hb levels [24 weeks]
The change from baseline of CBF will be correlated to the corresponding post-baseline assessment for change in Hb.
- Relationship between oxygen ejection fraction (OEF) and change in Hb levels [24 weeks]
The change from baseline of OEF will be correlated to the corresponding post-baseline assessment for change in Hb.
- Relationship between cerebral metabolic rate of oxygen (CMRO2) and change in Hb levels [24 weeks]
The change from baseline of CMRO2 will be correlated to the corresponding post-baseline assessment for change in Hb.
- Adverse events in participants with SCD [24 weeks]
Maximum intensity of treatment emergent adverse events (TEAEs) will be summarized by system organ class and preferred term. The tabulation of deaths, serious TEAEs, serious drug-related TEAEs and TEAEs leading to study drug discontinuation will also be provided
Eligibility Criteria
Criteria
Inclusion Criteria:
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Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta0 thalassemia (HbS/β0 thal)
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Hemoglobin (Hb): Hb ≤ 9.0 g/dL at baseline
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Concomitant hydroxyurea (HU) therapy is allowed if the dose has been stable for at least 3 months with no anticipated need for dose adjustments during the study and no sign of hematological toxicity
Exclusion Criteria:
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Any one of the following requiring a medical facility visit within 14 days prior to signing the informed consent form:
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Vaso-occlusive crisis (VOC)
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Acute chest syndrome (ACS)
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Splenic sequestration
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Dactylitis
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Requires chronic transfusion therapy
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Abnormal TCD in the last 12 months
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RBC transfusion within 60 days of screening
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Severe renal dysfunction at the Screening Visit or on chronic dialysis
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Hepatic dysfunction
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Clinically relevant cardiac or pulmonary disease- e.g., congenital heart defect, uncompensated heart failure, or any unstable cardiac condition, arrhythmic heart condition, pulmonary fibrosis, pulmonary hypertension
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Major surgery involving the stomach or small intestine
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Chemotherapy or radiation within the past 2 years
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History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
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Clinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapy
-
Female who is breast feeding or pregnant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Emory University Children's Healthcare of Atlanta | Atlanta | Georgia | United States | 30342 |
Sponsors and Collaborators
- Forma Therapeutics, Inc.
- Emory University
Investigators
- Study Director: Vandy Black, MD, MSc, Forma Therapeutics, Inc.
- Principal Investigator: Amy Tang, MD, Children's Healthcare of Atlanta
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FT-4202-CBF