A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose-Finding Study and Open-Label Extension of SC411 in Children With Sickle Cell Disease
Overview
- Phase
- Phase 2
- Intervention
- Docosahexaenoic Acid
- Conditions
- Sickle Cell Disease
- Sponsor
- Micelle BioPharma Inc
- Enrollment
- 68
- Locations
- 11
- Primary Endpoint
- Evaluate safety & tolerability of SC411 & determine change from Baseline in the blood cells omega-3 fatty acids index in subjects, treated with active SC411 doses or placebo in Part A and safety and tolerability in Part B.
- Last Updated
- 7 years ago
Overview
Brief Summary
This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study of SC411 in children with sickle cell disease (SCD). The primary objective of the study is to evaluate the safety and tolerability of three different doses of SC411 compared to a placebo. All patients will undergo eight weeks of oral study treatment and a four-week safety follow-up period. Patients will be randomized to one of three dose levels of SC411 or placebo.
Detailed Description
This Phase 2 study is to be conducted in two parts. Part A is a randomized, double-blind, placebo-controlled, parallel-group, dose-finding study of SC411 in children with SCD. This part of the study will consist of a screening period of up to 2 weeks, followed by an eight-week treatment period. Part B is an optional 49-month open-label extension for patients who have completed Part A.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged greater than or equal to 5 years and less than or equal to 17 years at screening;
- •Has been diagnosed with SCD that includes the phenotypes HbSS, hemoglobin SC, and HbS/beta-thalassemia. Hemoglobin phenotyping must be previously documented by either hemoglobin high-performance liquid chromatography \[HPLC\] or electrophoresis at time of Screening. If a patient does not have documented hemoglobin phenotyping at the time of Screening, or has received a blood transfusion within the two months prior to the Screening Visit, hemoglobin phenotyping should be documented by hemoglobin HPLC;
- •Has had at least two and no more than ten documented episodes of clinical sickle cell crises within 12 months prior to the Screening Visit. A sickle cell crisis is defined as an episode of vaso-occlusive event:
- •Painful crisis defined as new onset of pain that lasts two or more hours for which there is no explanation other than vaso-occlusion, and which requires therapy with oral or parenteral opioids, non-steroidal anti-inflammatory drugs, or other analgesics prescribed by a healthcare provider in a medical setting such as a hospital, clinic, or emergency room visit, or documented telephone management (Ballas, 2010; Heeney, 2016; Jacob, 2005); and
- •Acute chest syndrome defined as acute illness characterized by a new segmental pulmonary infiltrate on a chest x-ray, and fever (greater than or equal to 38.5°C) or respiratory symptoms such as hypoxia, chest pain, tachypnea, wheezing, or cough (Ballas, 2010);
- •Is either not on hydroxyurea at the Screening Visit and does not plan on receiving it during the course of the first 12 weeks of the study (Part A), or has received hydroxyurea for a minimum of 6 months and, except for safety reasons, will remain on the same weight-based dose of hydroxyurea from screening throughout the duration of Part A of the study;
- •Parent or guardian is able to give written informed consent, and the potential pediatric patient is able to provide assent in a manner approved by the Institutional Review Board (IRB) and comply with the requirements of the study other than for safety reasons; and
- •If sexually active, agrees to use a reliable method of birth control (eg, barrier, birth control pills, abstinence) during the study and for one month following the last dose of study drug.
Exclusion Criteria
- •Has a significant medical condition that required hospitalization (other than sickle cell crisis) within two months of the Screening Visit;
- •Has a known allergy or hypersensitivity to fish or shellfish;
- •Has a known allergy or hypersensitivity to soy;
- •Is planning to initiate, terminate, or alter the dosing of hydroxyurea during the first 12 weeks of the study, other than for safety reasons;
- •Has chronic daily use (more than 30 consecutive days during the last six months prior to enrollment) of opioid analgesia for any reason;
- •Has a diagnosis of chronic pain or chronic pain syndrome (eg, chronic pain from the repeated vaso-occlusive events, chronic pain from avascular necrosis);
- •Has a history of Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection;
- •Has a history of documented episode(s) of priapism within 12 months of the Screening Visit;
- •Has a history of atrial or ventricular arrhythmia;
- •Has an international normalized ratio (INR) \>2.0, or is on regular anticoagulation therapy, or has a history of a known bleeding diathesis;
Arms & Interventions
Dose Level 1
Target dose 20 mg/kg Docosahexaenoic acid
Intervention: Docosahexaenoic Acid
Dose Level 2
Target dose 36 mg/kg Docosahexaenoic acid
Intervention: Docosahexaenoic Acid
Dose Level 3
Target dose 60 mg/kg Docosahexaenoic acid
Intervention: Docosahexaenoic Acid
Placebo
Soybean oil
Intervention: Placebo
Outcomes
Primary Outcomes
Evaluate safety & tolerability of SC411 & determine change from Baseline in the blood cells omega-3 fatty acids index in subjects, treated with active SC411 doses or placebo in Part A and safety and tolerability in Part B.
Time Frame: Week 0 (baseline) through Month 52 (end of treatment)
Evaluate the safety and tolerability of three different doses of SC411 and determine the change from Baseline in the blood cells omega-3 fatty acids index in subjects, treated with either one of the three active doses of SC411 or matching placebo in Part A. Safety and tolerability will continue to be evaluated and reported during Part B.
Secondary Outcomes
- Measurement of the pharmacokinetic (PK) parameter of AUC will be performed for three dose levels of SC411 will be measured.(2 weeks before baseline (screening) through Week 52)
- Measurement of the pharmacokinetic (PK) parameter of Tmax will be performed for three dose levels of SC411 will be measured.(2 weeks before baseline (screening) through Week 52)
- Measurement of the pharmacokinetic (PK) parameter of Cmax will be performed for three dose levels of SC411 will be measured.(2 weeks before baseline (screening) through Week 52)
- The safety & long term tolerability of SC411 will be evaluated in Part A, & a selected dose in Part B. The change from Baseline in blood cells omega-3 fatty acids index in subjects, treated with SC411 or placebo in Part A will be determined.(Week 0 (baseline) through Month 52 (end of treatment))