- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05953584
A Phase 2 Open-label Study to Evaluate the Activity of Etavopivat on Transcranial Doppler Velocities in Pediatric Patients With Sickle Cell Disease Who Are at Increased Risk for Primary Stroke
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Novo Nordisk
- Phone Number: (+1) 866-867-7178
- Email: clinicaltrials@novonordisk.com
Study Locations
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Delhi
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New Delhi, Delhi, India, 110029
- Not yet recruiting
- All India Institute of Medical Sciences
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Raipur, Delhi, India, 110029
- Not yet recruiting
- All India Institute of Medical Sciences
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Contact:
- All IIOM Sciences
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Gujarat
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Sūrat, Gujarat, India
- Not yet recruiting
- Nirmal Hospital
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Maharashtra
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Nagpur, Maharashtra, India, 440012
- Not yet recruiting
- Indira Gandhi Government Medical College & Hospital
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Contact:
- Suretech HARC Ltd.
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Nagpur, Maharashtra, India, 440012
- Not yet recruiting
- Suretech Hospital and Research Centre Ltd.
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Ibadan, Nigeria
- Not yet recruiting
- The University of Ibadan University College Hospital
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Kano, Nigeria
- Not yet recruiting
- Aminu Kanu Teaching Hospital
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Lagos, Nigeria
- Not yet recruiting
- Lagos University Teaching Hospital
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Muscat
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Al-khoudh PC 123, Muscat, Muscat, Oman
- Recruiting
- Sultan Qaboos University Hospital
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Contact:
- Sultan QU Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Patient's parent, legal guardian, or legal representative has provided documented informed consent and patients have provided age-appropriate assent
Age:
12 to 16 years of age (inclusive) at time of screening
Type of Participant and Disease Characteristics:
Confirmed diagnosis of SCD
• Documentation of SCD genotype (HbSS, HbSβ0 -thalassemia) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography, or similar testing.
- TAMMV greater than or equal to (≥) 170 cm/s in the ICA and/or MCA during the Screening Period and confirmed on 2 occasions and without history of primary ischemic or hemorrhagic stroke, transient ischemic attack, or severe central nervous system (CNS) vasculopathy on magnetic resonance angiography (MRA). This includes patients with cTCD (170-199 centimeter per second [cm/s]) or aTCD (≥ 200 cm/s). Patients in the aTCD cohort must refuse transfusion therapy.
- Hb ≥ 6 grams per deciliter (g/dL) and lesser than or equal to (≤) 9 g/dL at screening
For participants with aTCD and cTCD and already taking HU, the dose of HU milligram per kilogram (mg/kg) must be stable (no more than a 20% change in dosing except for weight-based changes) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments except for weight-based changes during the study, in the opinion of the Investigator.
Sex and Contraceptive Requirements
- Patients, who if female and of childbearing potential, are using acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male, are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug.
Exclusion Criteria:
Medical Conditions
- Female who is breast feeding or pregnant
- History of seizure disorder
- Prior overt stroke (a focal neurological deficit of acute onset) by history or evidence on Screening MRI, history of transient ischemic attack, focal neurological deficit on standardized neurological examination, or concern for moderate or severe neurological deficit (which could be due to stroke) based on a positive "10 questions" screening. Patients with significant or suggestive severe CNS vasculopathy (ie, moya moya) of Grade 4 or higher based on MRA read locally.
- Significant cytopenias (absolute neutrophil count [ANC] < 1.5 × 10^3/microliter (µL), platelets < 150,000/µL, reticulocytes < 80,000/µL)
- Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m^2) or on chronic dialysis
- Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 4 × upper limit of normal (ULN) and/or direct bilirubin > 3 × ULN
Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy or history of such infections leading to significant neurological impairment:
- Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed.
- Patients with acute viral infections (eg, coronavirus disease 2019 [COVID-19]) should delay screening/enrollment until the acute infection has resolved.
- Patients enrolled in areas where malaria is prevalent must be on malaria prophylaxis based on regional guidance and resistance results. Note: Infection prophylaxis is allowed (see concomitant medication restrictions).
- Known human immunodeficiency virus (HIV) positivity
- Known infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Etavopivat
Participants will receive Etavopivat 400 mg once daily (QD) orally.
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Participants will receive a dose of 400 mg (two 200 mg oral tablets) etavopivat once daily.
Participants will receive a stable dose of HU.
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Experimental: Etavopivat with HU
Participants will receive Etavopivat 400 mg QD orally in combination with HU.
The dose of HU (mg/kg) will be stable (no more than a 20% change in dosing except for weight-based changes) during the study, in the opinion of the Investigator.
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Participants will receive a stable dose of HU.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in the timed-average-mean-maximum-velocity (TAMMV) arterial cerebral blood flow of index artery (L/R internal carotid artery [ICA], L/R middle cerebral artery [MCA]) at Week 12 versus baseline, as measured by TCD
Time Frame: Baseline and Week 12
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Baseline and Week 12
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change in TAMMV at Weeks 2, 4, 24, and 52 versus baseline, as measured by TCD
Time Frame: Baseline, Weeks 2,4, 24 and 52
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Baseline, Weeks 2,4, 24 and 52
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Incidence of conversion to normal (< 170 cm/s), conditionally abnormal (170-199 cm/s), and abnormal (≥ 200 cm/s) TCD velocities
Time Frame: Weeks 2, 4, 12, 24, and 52
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Weeks 2, 4, 12, 24, and 52
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Clinical Transparency (dept. 2834), Novo Nordisk A/S
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 4202-HEM-204
- PACTR202301655446404 (Registry Identifier: Pan African Clinical Trial Registry)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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