Sickle Cell Disease
Conditions
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.
Interventions
DRUGEtavopivat
The study intervention is etavopivat (400 mg), administered orally and once daily (QD)
Sponsors
Novo Nordisk A/S
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of etavopivat on cerebral blood flow (CBF) | 24 weeks | 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) | 24 weeks | 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) | 24 weeks | Change in CMRO2 assessments from baseline will be summarized with descriptive statistics by nominal study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relationship between CBF and change in Hb levels | 24 weeks | 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 | 24 weeks | 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 | 24 weeks | 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 | 24 weeks | 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 |
| Muscle hemodynamic effect of etavopivat on muscle blood flow | 24 weeks | Change in muscle blood flow assessments from baseline will be summarized with descriptive statistics by nominal study visit. |
| Muscle hemodynamic effect of etavopivat on oxygen ejection fraction (OEF) | 24 weeks | Change in OEF from baseline will be summarized with descriptive statistics by nominal study visit. |
| Muscle hemodynamic effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2) | 24 weeks | Change in CMRO2 from baseline will be summarized with descriptive statistics by nominal study visit. |
Countries
United States
Contacts
STUDY_DIRECTORClinical Transparency dept. 2834
Novo Nordisk A/S
PRINCIPAL_INVESTIGATORAmy Tang, MD
Children's Healthcare of Atlanta
Outcome results
None listed