Back to resultsStudy of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease
Primary Purpose
Sickle Cell Disease
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Etavopivat
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease
Eligibility Criteria
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
Sites / Locations
- Emory University Children's Healthcare of Atlanta
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Etavopivat
Arm Description
Single-arm, open-label
Outcomes
Primary Outcome Measures
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.
Effect of etavopivat on oxygen ejection fraction (OEF)
Change in OEF assessments from baseline will be summarized with descriptive statistics by nominal study visit.
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.
Secondary Outcome Measures
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.
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.
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.
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
Full Information
NCT ID
NCT05725902
First Posted
January 23, 2023
Last Updated
March 20, 2023
Sponsor
Novo Nordisk A/S
Collaborators
Emory University
1. Study Identification
Unique Protocol Identification Number
NCT05725902
Brief Title
Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease
Official Title
A Pilot Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
March 15, 2023 (Anticipated)
Primary Completion Date
October 15, 2024 (Anticipated)
Study Completion Date
December 15, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
Collaborators
Emory University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Etavopivat
Arm Type
Experimental
Arm Description
Single-arm, open-label
Intervention Type
Drug
Intervention Name(s)
Etavopivat
Other Intervention Name(s)
FT-4202
Intervention Description
The study intervention is etavopivat (400 mg), administered orally and once daily (QD)
Primary Outcome Measure Information:
Title
Effect of etavopivat on cerebral blood flow (CBF)
Description
Change in cerebral blood flow (CBF) assessments from baseline will be summarized with descriptive statistics by nominal study visit.
Time Frame
24 weeks
Title
Effect of etavopivat on oxygen ejection fraction (OEF)
Description
Change in OEF assessments from baseline will be summarized with descriptive statistics by nominal study visit.
Time Frame
24 weeks
Title
Effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)
Description
Change in CMRO2 assessments from baseline will be summarized with descriptive statistics by nominal study visit.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Relationship between CBF and change in Hb levels
Description
The change from baseline of CBF will be correlated to the corresponding post-baseline assessment for change in Hb.
Time Frame
24 weeks
Title
Relationship between oxygen ejection fraction (OEF) and change in Hb levels
Description
The change from baseline of OEF will be correlated to the corresponding post-baseline assessment for change in Hb.
Time Frame
24 weeks
Title
Relationship between cerebral metabolic rate of oxygen (CMRO2) and change in Hb levels
Description
The change from baseline of CMRO2 will be correlated to the corresponding post-baseline assessment for change in Hb.
Time Frame
24 weeks
Title
Adverse events in participants with SCD
Description
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
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amy Tang, MD
Phone
+1-404-785-3518
Email
amy.tang@choa.org
First Name & Middle Initial & Last Name or Official Title & Degree
Erin Buckley, PhD
Phone
+1 404-727-4323
Email
erin.buckley@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vandy Black, MD, MSc
Organizational Affiliation
Forma Therapeutics
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Amy Tang, MD
Organizational Affiliation
Children's Healthcare of Atlanta
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory University Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erin M Buckley, PhD
Phone
404-727-4323
Email
erin.buckley@emory.edu
First Name & Middle Initial & Last Name & Degree
Amy Tang, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease
We'll reach out to this number within 24 hrs