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

Publication date: Available online 23 January 2019

Source: The Journal of Allergy and Clinical Immunology: In Practice

Author(s): William R. Lumry, Inmaculada Martinez-Saguer, William H. Yang, Jonathan A. Bernstein, Joshua Jacobs, Dumitru Moldovan, Marc A. Riedl, Douglas T. Johnston, H.Henry Li, Yongqiang Tang, Jennifer Schranz, Peng Lu, Moshe Vardi, Henriette Farkas, SAHARA study group

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. Primary efficacy endpoint was normalized number of attacks (NNA) versus placebo. Key additional endpoints were proportion of patients achieving NNA reduction ≥50%, attack severity, number of attack-free days, and safety.

Results

75 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).

Conclusion

Fixed-dose subcutaneous pdC1-INH liquid was superior to placebo in preventing HAE attacks and demonstrated a favorable safety profile.

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