SCDAA 46th Annual National Convention

Abstract 

Authors:
Dr. Ofelia Alvarez- University of Miami, Dr. Ahmed Daak- SCI, Dr. Matthew Heeney- Dana-Farber / Boston Children's Cancer and Blood Disorders Center, Harvard Medical School, Dr. Beng Fuh- East Carolina University Department of Pediatrics, Dr. Carlton Dampier-Emory University School of Medicine, Dr. Julie Kanter- Division of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA, 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

Background:
Docosahexaenoic acid (DHA) is a bioactive omega-3 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 patients with SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology® (ALT®)) that enhances DHA bioavailability. The SCOT trial is a phase 2 randomized placebo-controlled double-blinded study followed by an open label extension phase (OLE).
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 six months prior to screening were enrolled. Subjects received either placebo or one of three doses of SC411 (20 [12-26]; 36 [26-48] or 60 [51-72] mg/kg/day DHA) for two months. Subjects who consented to the OLE were rolled into the lowest dose level (20 mg/Kg). The annualized rates of SCC against baseline were analyzed using a Poisson regression model with a log-link and with treatment, baseline disease severity, age group, and hydroxyurea use as covariates, and subject as a repeated measure. The model uses the log of (days in the study / 365) as the offset variable to produce the annualized rates. The percentage of subjects who remained crisis-free for at least 300 days post-randomization at the time of this analysis, was also reported. Safety and tolerability are reported.
Results:
A total of 67 subjects, 34 of whom are female (50.7%), were randomized to one of the three active groups (n=50) or placebo (n=17). Subjects on HU treatment constituted 76% of total study population. Sixty-two subjects (93%) completed the blinded portion of the study. Forty-one subjects (66%) opted into the OLE. Of all subjects in the OLE, seven (17.07%) received placebo during the blinded part of the study. At the time of this analysis, thirty-eight subjects have completed at least 300 days in the study and thirteen patients have completed one year. No unexpected or treatment-related adverse events were reported.
The median annualized rate of SCC at baseline for the subjects who enrolled into the study (n=67) or the OLE (n=41) was 3.00. The rate ratios of SCC of the year post versus the year prior to randomization were 0.560 (95% confidence interval [CI]: 0.39 to 0.80; p=0.0016) for the group who was on active drug during the blinded part (n=34), and 0.53 (CI: 0.66 to 0.79, p=0.0017) for patients who were on active treatment for a period of at least 6 months (n=32).
300 days after randomization, 40% of the patients (15/38) remained crisis-free. Of the 13 patients that have completed over one year of treatment, five (38.46%) are crisis free.
Conclusions:
The SCOT OLE study provides additional evidence that SC411 is safe and well-tolerated. Subjects on a dose of 20 mg/Kg DHA of SC411 experienced a significantly lower rate of sickle cell crises compared to the year prior to enrollment.