Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

A Pilot Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05725902
• Other study ID #: FT-4202-CBF
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 4, 2024
• Est. completion date: August 15, 2025

Study information

• Verified date: February 2024
• Source: Novo Nordisk A/S
• Contact: Amy Tang, MD
• Phone: +1-404-785-3518
• Email: amy.tang[@]choa.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An open-label, single arm study in patients 12 to 21 years of age with SCD to evaluate the effects of etavopivat on cerebral and muscle hemodynamics.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: August 15, 2025
• Est. primary completion date: June 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 21 Years

Eligibility

Inclusion Criteria:

• Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta0 thalassemia (HbS/ß0 thal)

• Hemoglobin (Hb): Hb = 9.0 g/dL at baseline

• 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:

• Any one of the following requiring a medical facility visit within 14 days prior to signing the informed consent form:

• Vaso-occlusive crisis (VOC)

• Acute chest syndrome (ACS)

• Splenic sequestration

• Dactylitis

• Requires chronic transfusion therapy

• Abnormal TCD in the last 12 months

• RBC transfusion within 60 days of screening

• Severe renal dysfunction at the Screening Visit or on chronic dialysis

• Hepatic dysfunction

• 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

• Major surgery involving the stomach or small intestine

• Chemotherapy or radiation within the past 2 years

• History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage

• Clinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapy

• Female who is breast feeding or pregnant

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Etavopivat
The study intervention is etavopivat (400 mg), administered orally and once daily (QD)

Locations

Country	Name	City	State
United States	Emory University Children's Healthcare of Atlanta	Atlanta	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
Forma Therapeutics, Inc.	Emory University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effect of etavopivat on cerebral blood flow (CBF)	Change in cerebral blood flow (CBF) assessments from baseline will be summarized with descriptive statistics by nominal study visit.	24 weeks
Primary	Effect of etavopivat on oxygen ejection fraction (OEF)	Change in OEF assessments from baseline will be summarized with descriptive statistics by nominal study visit.	24 weeks
Primary	Effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)	Change in CMRO2 assessments from baseline will be summarized with descriptive statistics by nominal study visit.	24 weeks
Secondary	Relationship between CBF and change in Hb levels	The change from baseline of CBF will be correlated to the corresponding post-baseline assessment for change in Hb.	24 weeks
Secondary	Relationship between oxygen ejection fraction (OEF) and change in Hb levels	The change from baseline of OEF will be correlated to the corresponding post-baseline assessment for change in Hb.	24 weeks
Secondary	Relationship between cerebral metabolic rate of oxygen (CMRO2) and change in Hb levels	The change from baseline of CMRO2 will be correlated to the corresponding post-baseline assessment for change in Hb.	24 weeks
Secondary	Adverse events in participants with SCD	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	24 weeks