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

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Etavopivat

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Emory University Children's Healthcare of Atlanta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta0 thalassemia (HbS/β0 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: FT-4202

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Muscle hemodynamic effect of etavopivat on muscle blood flow	Change in muscle blood flow assessments from baseline will be summarized with descriptive statistics by nominal study visit.	24 weeks
Muscle hemodynamic effect of etavopivat on oxygen ejection fraction (OEF)	Change in OEF from baseline will be summarized with descriptive statistics by nominal study visit.	24 weeks
Muscle hemodynamic effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)	Change in CMRO2 from baseline will be summarized with descriptive statistics by nominal study visit.	24 weeks

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Collaborators: Emory University
• Investigators: Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S; Principal Investigator: Amy Tang, MD, Children's Healthcare of Atlanta

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2024
• Primary Completion (Actual): March 9, 2026
• Study Completion (Actual): March 9, 2026

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: February 10, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell
• Other Study ID Numbers: FT-4202-CBF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No