Haematological Disorders
Conditions
Interventions
Etavopivat in combination with HU
Sponsors
Forma Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all the following criteria apply: Informed Consent 1. Patient’s parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent Age 2. 12 to 16 years of age (inclusive) at time of Screening Type of Participant and Disease Characteristics 3. Confirmed diagnosis of SCD • Documentation of SCD genotype (HbSS, HbSß0 -thalassemia) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography, or similar testing. Note that Hb electrophoresis, and other forms of Hb subtype quantification, is performed by the local laboratory at Screening. 4. TAMMV = 170 cm/s in the ICA and/or MCA during the Screening Period and confirmed on 2 occasions and without history of primary ischemic or hemorrhagic stroke, transient ischemic attack, or severe CNS vasculopathy on magnetic resonance angiography (MRA). This includes patients with cTCD (170-199 cm/s) or aTCD (= 200 cm/s). Patients in the aTCD cohort must refuse transfusion therapy. 5. Hb = 6 g/dL and = 9 g/dL at Screening 6. For participants with aTCD and cTCD and already taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing except for weight-based changes) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments except for weight-based changes during the study, in the opinion of the Investigator. Sex and Contraceptive Requirements 7. Patients, who if female and of childbearing potential, are using acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male, are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug
Exclusion criteria
Exclusion criteria: Patients are excluded from the study if they meet any of the following criteria: Medical Conditions 1. Female who is breast feeding or pregnant 2. History of seizure disorder 3. Prior overt stroke (a focal neurological deficit of acute onset) by history or evidence on Screening MRI, history of transient ischemic attack, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive “10 questions” screening. Patients with significant or suggestive severe CNS vasculopathy (ie, moya moya) of Grade 4 or higher based on MRA read locally. 4. Significant cytopenias (absolute neutrophil count [ANC] 4 × upper limit of normal (ULN) and/or direct bilirubin > 3 × ULN 7. Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy or history of such infections leading to significant neurological impairment: • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed. • Patients with acute viral infections (eg, coronavirus disease 2019 [COVID-19]) should delay screening/enrollment until the acute infection has resolved. • Patients enrolled in areas where malaria is prevalent must be on malaria prophylaxis based on regional guidance and resistance results. Note: Infection prophylaxis is allowed (see concomitant medication restrictions). 8. Known human immunodeficiency virus (HIV) positivity 9. Known infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepB
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in the TAMMV arterial cerebral blood flow of index artery (L/R internal carotid artery [ICA], L/R middle cerebral artery [MCA]) at Week 12 versus baseline, as measured by TCD | — |
Secondary
| Measure | Time frame |
|---|---|
| Change in TAMMV at Weeks 2, 4, 24, and 52 versus baseline, as measured by TCD; Incidence of conversion to normal (< 170 cm/s), conditionally abnormal (170-199 cm/s), and abnormal (= 200 cm/s) TCD velocities | — |
Countries
Nigeria
Contacts
Public ContactMichelle Botha
Regulatory
Outcome results
None listed