A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients with Sickle Cell Disease who are at Increased Risk for Primary Stroke
- Conditions
- Haematological Disorders
- Registration Number
- PACTR202301655446404
- Lead Sponsor
- Forma Therapeutics Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 46
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
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] < 1.5 × 103/µL, platelets < 150,000/µL, reticulocytes < 80,000/µL)
5. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m2) or on chronic dialysis
6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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<br><br>