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Clinical Trial
. 2020 Sep 1;33(3):136-141.
doi: 10.1089/ped.2020.1143. Epub 2020 Sep 16.

Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema

Donald Levy  1 , Teresa Caballero  2 , Iftikhar Hussain  3 , Avner Reshef  4 , John Anderson  5 , James Baker  6 , Lawrence B Schwartz  7 , Marco Cicardi  8 , Subhransu Prusty  9 , Henrike Feuersenger  9 , Ingo Pragst  9 , Michael E Manning  10
Affiliations
Clinical Trial

Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema

Donald Levy et al. Pediatr Allergy Immunol Pulmonol. .

Abstract

Background: Hereditary angioedema (HAE) due to C1 inhibitor (C1INH) deficiency is characterized by recurrent attacks of edema of the skin and mucosal tissues. Symptoms usually present during childhood (mean age at first attack, 10 years). Earlier symptom onset may predict a more severe disease course. Subcutaneous (SC) C1INH is indicated for routine prophylaxis to prevent HAE attacks in adolescents and adults. We analyzed the long-term efficacy of C1INH (SC) in subjects ≤17 years old treated in an open-label extension (OLE) of the pivotal phase III Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1 Inhibitor Replacement Therapy (COMPACT) trial. Methods: Eligible subjects (age ≥6 years, with ≥4 attacks over 2 consecutive months before entry into the OLE or placebo-controlled COMPACT trial) were treated with C1INH (SC) 40 or 60 IU/kg twice weekly for 52-140 weeks. Subgroup analyses by age (≤17 vs. >17 years) were performed for key efficacy endpoints. Results: Ten subjects were ≤17 years old [mean (range) age, 13.3 (8-16) years, 3 subjects <12 years old; exposure range, 51-133 weeks]. All 10 pediatric subjects experienced ≥50% reduction (mean, 93%) in number of attacks versus the prestudy period, with a 97% reduction in the median number of attacks/month (0.11). All subjects had <1 attack/4-week period and 4 had <1 attack/year (1 subject was attack free). No subject discontinued treatment due to a treatment-related adverse event. Conclusions: Data from pediatric subjects treated with C1INH (SC) for up to 2.55 years and adult subjects revealed similar efficacy. C1INH (SC) is effective and well tolerated as long-term prophylaxis in children, adolescents, and adults with HAE.

Keywords: C1 inhibitor; COMPACT; Haegarda; children; hereditary angioedema; long term; pediatric; prophylaxis; quality of life; safety.

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Conflict of interest statement

Donald S. Levy, is a consultant with Takeda, Biocryst, CSL Behring, Pharming; is a speaker for Takeda and CSL Behring; has received clinical research grants from CSL Behring. Teresa Caballero has received grant research, grant support and/or speaker/consultancy fees from BioCryst, CSL Behring, Merck, Novartis, Octapharma, Pharming, and Shire (a Takeda company); has received funding to attend conferences/educational events from CSL Behring, Novartis and Shire; is/has been a clinical trial/registry investigator for Biocryst, CSL Behring, Novartis, Pharming and Shire; and is a researcher from the IdiPAZ program for promoting research activities. Iftikhar Hussain is a speaker for CSL Behring, Grifols, and Optionse; is/has been on the advisory board for Blueprint Medicine and Pfizer; is Principal Investigator for Adare, Sanofi, Cara Therapeutics, Dermira, Lilly, Pfizer, Abbvie, CSL Behring, Astra-Zeneca, and Genentech, ALK. Avner Reshef has received research funding, travel grants, and/or speaker honorarium-consultation fee from CSL-Behring, Pharming, BioCryst, Takeda-Shire, Teva, Stallergens. John Anderson has potential conflicts of interest with CSL Behring, Takeda, BioCryst. James Baker has no conflicts of interest. Lawrence B. Schwartz is/has been HAE clinical trial principal investigator for CSL Behring and Takeda; is/has been on the advisory board for CSL Behring LLC, Takeda Pharmaceuticals, Pharming Healthcare, and BioCryst Pharmaceuticals. Marco Cicardi has potential conflicts of interest with CSL Behring, Shire, and Pharming. Subhransu Prusty, Henrike Feuersenger, and Ingo Pragst are/have been CSL Behring employees. Michael Manning has received grant support from CSL Behring, Takeda/Shire, BioCryst, and KalVista; is a speaker for CSL Behring, Takeda/Shire, and Pharming; is a consultant with and on the advisory boards for CSL Behring, Takeda/Shire, BioCryst, and Pharming.

Figures

FIG. 1.
FIG. 1.
COMPACT OLE study design. COMPACT, Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1 Inhibitor Replacement Therapy; OLE, open-label extension; TP, treatment period.
FIG. 2.
FIG. 2.
Efficacy in pediatric and adult subjects treated long term with C1INH (SC). C1INH (SC), subcutaneous C1 inhibitor.
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