Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE: SAHARA Randomized Study

SAHARA study group

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13 Scopus citations

Abstract

Background: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues. Objective: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959). Methods: Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre–long-term prophylaxis. In a partial crossover design, 80% of patients were randomized to placebo or pdC1-INH liquid for 14 weeks and crossed over from active to placebo or vice versa for another 14 weeks. The remainder were randomized to pdC1-INH liquid for 28 weeks. The primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were the proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety. Results: Seventy-five patients were randomized and 58 (77%) completed the study. Mean age 41 years; 88% HAE type I. Least-squares means of NNA were reduced from 3.9 with placebo to 1.6 with pdC1-INH (from day 1; P < .0001). Most patients had ≥50% NNA reduction with pdC1-INH (from day 1, 78%). A total of 8.8% of placebo-treated patients were attack-free and 5.3%, 22.8%, and 63.2% had mild, moderate, and severe attacks, respectively; 37.5% of pdC1-INH–treated patients were attack-free and 8.9%, 26.8%, and 26.8% had mild, moderate, and severe attacks, respectively. Treatment-emergent adverse event rates were similar between groups (52% vs 56% for pdC1-INH crossover vs placebo, respectively). Conclusions: Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.

Original languageEnglish
Pages (from-to)1610-1618.e4
JournalJournal of Allergy and Clinical Immunology: In Practice
Volume7
Issue number5
DOIs
StatePublished - 1 May 2019

Funding

FundersFunder number
Alnylam
Excel Medical Affairs
Shire Human Genetic Therapies, Inc.
US HAE Association
US Hereditary Angioedema Association
Pfizer
AstraZeneca
Genentech
GlaxoSmithKline
Merck
Novartis
Roche
Sanofi
3M
Teva Pharmaceutical Industries
CSL Behring
Regeneron Pharmaceuticals
BioCryst
Shire
Galderma
Swedish Orphan Biovitrum

    Keywords

    • Fixed-dose
    • Hereditary angioedema
    • Liquid
    • Long-term prophylactic treatment
    • SAHARA study
    • Subcutaneous

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