Pharmacokinetics, Pharmacodynamics and Safety of Epeleuton in Patients With Sickle Cell Disease

Study Overview
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Brief Summary
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To assess the pharmacokinetics, pharmacodynamics and safety of Epeleuton capsules in adult SCD patients who are aged ≥18 years.

Detailed Description
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The trial will consist of a 28-day screening period, 16 weeks of active treatment and a 30-day post-treatment follow-up period.

Official Title
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An Open-label Mechanistic Study to Assess the Pharmacokinetics, Pharmacodynamics and Safety of Orally Administered Epeleuton in Patients With Sickle Cell Disease

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: Epeleuton


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with sickle cell disease (SCD) including: 2 sickle hemoglobin genes [HbSS] and HbSβ0-thalassemia Male or female patients aged 18 years and older on the day of signing the informed consent form (ICF) Patients who have had between 2 and 10 episodes of vaso-occlusive crisis (VOC) in the past year (12 months) For patients taking hydroxyurea (HU), the dose of HU must be stable for at least 3 months prior to signing the ICD and with no anticipated need for dose adjustment during the study. Female patients and male patients with female partners of childbearing potential must use highly effective contraceptive methods for the duration of the study. Exclusion Criteria: Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion), have received an RBC transfusion for any reason within three months of the randomization visit (baseline/day 0) or have a hemoglobin A level >20% of the total hemoglobin. Patients who have received a hematopoietic stem cell transplant. Patients with inadequate venous access as determined by the Investigator Patients who are pregnant, planning pregnancy, breastfeeding and/or are unwilling to use adequate contraception during the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epeleuton 4g/day<br> | Drug: Epeleuton<br>* Participants will receive 2000mg Epeleuton (DS102) capsules twice daily.<br>* Other names: DS102 Capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in P-selectin | Change in P-selectin from baseline at Week 16. | 16 Weeks | 
| Changes from baseline in Hemoglobin | Change in hemoglobin from baseline at Week 16 | 16 Weeks | 
| Changes from baseline in absolute reticulocyte count | Change in absolute reticulocyte count from baseline at Week 16. | 16 Weeks | 
| Changes from baseline in E-selectin | Change in E-selectin from baseline at Week 16. | 16 Weeks | 
| Changes from baseline in Phosphatidylserine | Change in Phosphatidlyserine from baseline to week 16. | 16 Weeks | 
| Changes from baseline in annualized rate of VOCs leading to a healthcare visit, and VOCs that are treated at home | Changes in annualized rate of VOCs leading to a healthcare visit, and VOCs that are treated at home from baseline to week 16 | 16 Weeks | 
| Changes from baseline in RBC Laminin Adhesion | Changes in RBC Laminin Adhesion from baseline to week 16 | 16 Weeks | 
| Changes from baseline in Leukocytes | Changes in Leukocytes from baseline to Week 16 | 16 Weeks | 
| Changes from baseline in Vascular Cell Adhesion Molecule 1 (VCAM-1) | Changes in VCAM-1 from baseline to Week 16 | 16 Weeks | 
| Changes from baseline in Dense Red Blood Cells | Changes in Dense Red Blood Cells from baseline to Week 16 | 16 Weeks | 
| Changes from baseline in Osmoscan | Changes in Osmoscan from baseline to Week 16 | 16 Weeks | 
| Changes from baseline in Oxygen Point of Sickling | Changes in Oxygen Point of Sickling from baseline to Week 16 | 16 Weeks | 
| Changes from baseline in D-dimer | Changes in D-dimer from baseline to Week 16 | 16 Weeks | 
| Change from baseline in PROMIS Pain Interference Short Form | Change in PROMIS Pain Interference from baseline to Week 16 | 16 Weeks | 
| Change from baseline in PROMIS Physical Activity Short Form | Change in PROMIS Physical Activity from baseline to Week 16 | 16 Weeks | 
| Trough plasma concentrations of total and unesterified 15 HEPE | Trough plasma concentrations of total and unesterified 15 HEPE at baseline and Week 16 | 16 Weeks | 
| Determination of exploratory biomarkers from baseline | Determination of exploratory biomarkers at baseline and Week 16 | 16 Weeks |