Health Condition 1: D573- Sickle-cell trait
Conditions
Interventions
Intervention1: Etavopivat: Cohort A: Single-agent etavopivat in patients with cTCD, or patients with aTCD (11 maximum patients with cTCD). Patients will be enrolled into a 52-week primary treatment pe
Sponsors
Forma Therapeutics Inc
Novo Nordisk India Private Limited
Eligibility
Inclusion criteria
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 a. Documentation of any SCD genotype (e.g. 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 Greater than or equal to 170 cm per s in the ICA and or MCA during the Screening Period and confirmed on 2 occasions (TCD No. 1 and No. 2; see Table 1 and Section 8.3.1) 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 per s) or aTCD (Greater than or equal to 200 cm per s). Note: Patients with aTCD must have refused transfusion therapy. 5. Hb Greater than or equal to 6g per dL and Lesser than or equal to 9 g per dL at Screening. 6. For participants with aTCD and cTCD and already taking HU, the dose of HU (mg per kg) must be stable (no more than a 20-percentage 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: 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. Concern for significant CNS injury, defined as one or more of the following: a. Prior overt stroke (a focal neurological deficit of acute onset) by history or significant concerns for history of overt stroke based on Screening MRI, b. History of transient ischemic attack, c. Focal neurological deficit on standardized neurological examination, d. Concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive “10 questions ? screening (see Section 8.1.2). e. Patients with significant or suggestive severe CNS vasculopathy (ie, moya moya, significant stenosis) of Grade 4 or higher based on MRA read locally. 4. Significant cytopenias (absolute neutrophil count [ANC] Lesser than 1.0 × 103 per µL, platelets Lesser than 100,000 per µL, hemoglobin Lesser than 8g per dL with reticulocytes Lesser than 80,000 per µL) 5. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory Lesser than 30 mL per min per 1.73 m2) or on chronic dialysis 6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) Greater than 4 × upper limit of normal (ULN) and or direct bilirubin Greater than 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: a. Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening or enrollment until active therapy has been completed. b. Patients with acute viral infections (e.g., coronavirus disease 2019 [COVID-19]) should delay screening/enrollment until the acute infection has resolved. c. 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 [HepBcAb] positive) 10. Positive Hepatitis C antibody 11. Untreated iron deficiency or other significant malnutrition detected or diagnosed by the Investigator 12. Significant malnutrition based on height, weight, BMI parameters or as deemed by the Investigator 13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable). 14. Hospitalized for sickle cell crisis or other VOC event within 14 days of time of consent or assent. Prior or Concomitant Therapy 15. Current use within 28 days of starting study treatment or planned treatment with additional disease modifying therapies (i.e, voxelotor, L-glutamine, and crizanlizumab), including plans for initiating HU after enrollment. For cohort A, patients must be off HU for at least 28 days prior to starting treatment. 16. Transfusion history restrictions defined as one or more of the following: <br/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the impact of etavopivat on TCD velocities in patients with aTCD or cTCD velocitiesTimepoint: Baseline and Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the change in TCD velocity over timeTimepoint: Baseline, Weeks 2, 4, 24 and 52;To evaluate changes in category of TCD velocity over timeTimepoint: Weeks 2, 4, 12, 24, and 52 | — |
Countries
India, Nigeria, Oman
Contacts
Public ContactDr Maya Sharma
Novo Nordisk India Private Limited
Outcome results
None listed