Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial)

Ahmed A. Daak, Carlton D. Dampier, Beng Fuh, Julie Kanter, Ofelia A. Alvarez, L. Vandy Black, Melissa A. McNaull, Michael U. Callaghan, Alex George, Lynne Neumayr, Lee M. Hilliard, Fredrick Sancilio, Adrian L. Rabinowicz, Matthew M. Heeney

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated the effect of 3 different doses of SC411 on clinical and biochemical endpoints in 67 children with SCD (5-17 years old). Seventy-six percent of subjects were also receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg DHA/kg per day or placebo a statistically significant (P, .001) mean percentage increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs baseline: 109.0% (confidence interval [CI], 46.7-171.3), 163.8% (CI, 108.3-219.2), 170.8% (CI, 90.2-251.4), and 28.6% (CI, 250.1 to 107.3), respectively. After 8 weeks of treatment, statistically significant changes vs placebo were also observed in D-dimer (P 5 .025) and soluble E-selectin (P 5 .0219) in subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411 significantly reduced electronic diary recorded SCC, analgesic use at home, and days absent from school because of sickle cell pain. The lower rate of clinical SCC observed in the pooled active groups vs placebo did not reach statistical significance (rate ratio, 0.47; 95% CI, 0.20-1.11; P = .07). All tested doses were safe and well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02973360.

Original languageEnglish (US)
Pages (from-to)1969-1979
Number of pages11
JournalBlood Advances
Volume2
Issue number15
DOIs
StatePublished - Aug 14 2018
Externally publishedYes

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Docosahexaenoic Acids
Sickle Cell Anemia
Confidence Intervals
Placebos
Blood Cells
Cell Membrane
E-Selectin
Eicosapentaenoic Acid
Hydroxyurea
Biological Availability
Analgesics
Hemoglobins
Oxidative Stress
Therapeutics
Inflammation
Technology
Lipids
Pain

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial). / Daak, Ahmed A.; Dampier, Carlton D.; Fuh, Beng; Kanter, Julie; Alvarez, Ofelia A.; Black, L. Vandy; McNaull, Melissa A.; Callaghan, Michael U.; George, Alex; Neumayr, Lynne; Hilliard, Lee M.; Sancilio, Fredrick; Rabinowicz, Adrian L.; Heeney, Matthew M.

In: Blood Advances, Vol. 2, No. 15, 14.08.2018, p. 1969-1979.

Research output: Contribution to journalArticle

Daak, AA, Dampier, CD, Fuh, B, Kanter, J, Alvarez, OA, Black, LV, McNaull, MA, Callaghan, MU, George, A, Neumayr, L, Hilliard, LM, Sancilio, F, Rabinowicz, AL & Heeney, MM 2018, 'Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial)', Blood Advances, vol. 2, no. 15, pp. 1969-1979. https://doi.org/10.1182/bloodadvances.2018021444
Daak, Ahmed A. ; Dampier, Carlton D. ; Fuh, Beng ; Kanter, Julie ; Alvarez, Ofelia A. ; Black, L. Vandy ; McNaull, Melissa A. ; Callaghan, Michael U. ; George, Alex ; Neumayr, Lynne ; Hilliard, Lee M. ; Sancilio, Fredrick ; Rabinowicz, Adrian L. ; Heeney, Matthew M. / Double-blind, randomized, multicenter phase 2 study of SC411 in children with sickle cell disease (SCOT trial). In: Blood Advances. 2018 ; Vol. 2, No. 15. pp. 1969-1979.
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abstract = "Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated the effect of 3 different doses of SC411 on clinical and biochemical endpoints in 67 children with SCD (5-17 years old). Seventy-six percent of subjects were also receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg DHA/kg per day or placebo a statistically significant (P, .001) mean percentage increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs baseline: 109.0{\%} (confidence interval [CI], 46.7-171.3), 163.8{\%} (CI, 108.3-219.2), 170.8{\%} (CI, 90.2-251.4), and 28.6{\%} (CI, 250.1 to 107.3), respectively. After 8 weeks of treatment, statistically significant changes vs placebo were also observed in D-dimer (P 5 .025) and soluble E-selectin (P 5 .0219) in subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411 significantly reduced electronic diary recorded SCC, analgesic use at home, and days absent from school because of sickle cell pain. The lower rate of clinical SCC observed in the pooled active groups vs placebo did not reach statistical significance (rate ratio, 0.47; 95{\%} CI, 0.20-1.11; P = .07). All tested doses were safe and well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT02973360.",
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