Clinical trial NCT05725902: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
Collaborators: name: Emory University
First posted: 2023-02-13
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Effect of etavopivat on cerebral blood flow (CBF)
timeFrame: 24 weeks
measure: Effect of etavopivat on oxygen ejection fraction (OEF)
timeFrame: 24 weeks
measure: Effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)
timeFrame: 24 weeks
Secondary outcomes:
measure: Relationship between CBF and change in Hb levels
timeFrame: 24 weeks
measure: Relationship between oxygen ejection fraction (OEF) and change in Hb levels
timeFrame: 24 weeks
measure: Relationship between cerebral metabolic rate of oxygen (CMRO2) and change in Hb levels
timeFrame: 24 weeks
measure: Adverse events in participants with SCD
timeFrame: 24 weeks
measure: Muscle hemodynamic effect of etavopivat on muscle blood flow
timeFrame: 24 weeks
measure: Muscle hemodynamic effect of etavopivat on oxygen ejection fraction (OEF)
timeFrame: 24 weeks
measure: Muscle hemodynamic effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Children's Healthcare of Atlanta
state: Georgia
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency dept. 2834
role: STUDY_DIRECTOR
affiliation: Children's Healthcare of Atlanta
name: Amy Tang, MD
role: PRINCIPAL_INVESTIGATOR
References: