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Celebrating Diversity Within the Sickle Cell Community: Commitment, Innovation, Practice
Saturday, October 13 • 9:00am - 9:15am
SC411 For Treatment Of Children With Sickle Cell Disease: A Phase 2, Randomized, Double-Blind, Dose-Finding, Placebo-Controlled, Parallel-Group, Multi-Center Study (Scot Trial)

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Abstract 

Authors:
Dr. Ahmed Daak- SCI, Dr. Matthew Heeney- Dana-Farber / Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Dr. Carlton Dampier- Emory University School of Medicine, Dr. Beng Fuh- East Carolina University Department of Pediatrics, Dr. Julie Kanter- Division of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA, Dr. Ofelia Alvarez- University of Miami, Dr. Vandy Black- University of Florida College of Medicine, Dr. Melissa Mcnaull- University of Mississippi Medical Center, Dr. Michael Callaghan- Children's Hospital of Michigan, Dr. Alex George- Texas Children’s Hospital

Introduction:
Blood cell membranes of patients with sickle cell disease (SCD) have low docosahexaenoic acid (DHA) levels. DHA is a bioactive fatty acid known to have potent anti-inflammatory, anti- blood cell adhesion and anti-oxidant properties. There is evidence that treatment with DHA reduces the rate of sickle cell crises (SCC) and ameliorates the chronic inflammation, oxidative stress and hypercoagulable state observed in SCD patients. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology® (ALT®)) that enhances DHA bioavailability. The SCOT trial investigated three different doses of SC411 in children with sickle cell disease.
Methods:
Children with SCD (HbSS, HbSC or S/β°‑thalassemia) aged 5-17 years (n=67), who had ≥2≤10 documented Sickle Cell Crises (SCC) during the 12 months prior to screening, and either had not received or who were on hydroxyurea (HU) for at least 6 months prior to screening, were enrolled. Subjects received either placebo or one of three increasing doses of SC411 (20; 36 or 60 mg/kg/day DHA, respectively) for two months. The effect of treatment with three dose levels of SC411 on selected clinical and biochemical parameters was investigated. Analysis was conducted under the Intention-To-Treat (ITT) population.
Results:
Sixty-seven (n=67) subjects were randomized, 50 to active treatment. Fifty-one (76%) were on HU treatment. Sixty-two patients (93%) completed the double-blinded phase of the study.
The analysis of the primary endpoint showed a mean percent increase from baseline in DHA and EPA concentration of 108.0 [CI: (49.5, 166.6)], 194.1 [CI: 145.8, 242.5)], 179.2 [CI (126.7, 231.6) and 15.4 [-42.8, 73.6)] in 20, 36 and 60 DHA mg/kg day and placebo, respectively, after 4 weeks of treatment.
After 8 weeks post-treatment, significant changes against placebo were observed in D-dimer (p=0.025) and sE-sel (p=0.0219) on patients exposed to 36 mg/kg. Significant increase in hemoglobin (Hb) against placebo was observed in those who received 20 mg/kg (p=0.039). Positive non-significant directional changes against placebo were observed in plasma hs-CRP, LDH, sVCAM and WBC count.
The adjusted eDiary-recorded incidence rate ratios (IRRs) of pooled active versus placebo were 0.65 (95% CI: 0.46, 0.93; p=0.02) for sickle cell crises, 0.75 (95% CI: 0.62, 0.92; p=0.0054) for analgesic use at home and 0.41 (95% CI: 0.31, 0.56; p=0.0001) for opioid use at home. The odds ratio of days absent from school because of sickle cell pain of active groups pooled versus placebo was 0.28 (95% CI: 0.19, 0.39; p=0.0002).
The rate of clinical SCC was 53% lower in the active groups pooled against placebo (rate ratio, 0.47; 95% confidence interval [CI]: 0.20 to 1.11; p=0.07).
Conclusions:
SC411 significantly reduced eDiary recorded sickle cell crises, analgesic and opioid use at home for sickle cell pain, and days absent from school due to sickle cell pain after two months of treatment. In addition, a non-statistically significant reduction of pain episodes and improvements in markers of inflammation, adhesion and coagulation were observed. These findings support further evaluation of the safety and efficacy of SC411 for SCD treatment in a phase 3 clinical trial


Saturday October 13, 2018 9:00am - 9:15am
Constellation B

Attendees (10)