Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE

SAHARA Randomized Study

SAHARA study group

Research output: Contribution to journalArticle

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

Fingerprint

Hereditary Angioedemas
Placebos
Safety
Therapeutics
Hereditary Angioedema Types I and II
Least-Squares Analysis
Cross-Over Studies

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy

Cite this

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

In: Journal of Allergy and Clinical Immunology: In Practice, Vol. 7, No. 5, 01.05.2019, p. 1610-1618.e4.

Research output: Contribution to journalArticle

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title = "Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE: SAHARA Randomized Study",
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.",
keywords = "Fixed-dose, Hereditary angioedema, Liquid, Long-term prophylactic treatment, SAHARA study, Subcutaneous",
author = "{SAHARA study group} and Lumry, {William R.} and Inmaculada Martinez-Saguer and Yang, {William H.} and Bernstein, {Jonathan A.} and Joshua Jacobs and Dumitru Moldovan and Riedl, {Marc A.} and Johnston, {Douglas T.} and Huamin Li and Yongqiang Tang and Jennifer Schranz and Peng Lu and Moshe Vardi and Henriette Farkas and P. Keith and W. Yang and M. Maurer and I. Martinez-Saguer and H. Farkas and A. Reshef and S. Kivity and D. Moldovan and T. Caballero and M. Guilarte and Hernandez, {M. D.} and Gonz{\'a}lez-Quevedo, {M. T.} and A. Banerji and J. Bernstein and A. Bewtra and T. Craig and S. Fineman and R. Gower and J. Jacobs and D. Johnston and J. Kashkin and Li, {H. H.} and Lumry, {W. R.} and M. Manning and D. McNeil and I. Melamed and N. Mumneh and T. Nickel and J. Panuto and D. Soteres and R. Tachdjian and J. Offenberger and J. Wedner",
year = "2019",
month = "5",
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language = "English (US)",
volume = "7",
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TY - JOUR

T1 - Fixed-Dose Subcutaneous C1-Inhibitor Liquid for Prophylactic Treatment of C1-INH-HAE

T2 - SAHARA Randomized Study

AU - SAHARA study group

AU - Lumry, William R.

AU - Martinez-Saguer, Inmaculada

AU - Yang, William H.

AU - Bernstein, Jonathan A.

AU - Jacobs, Joshua

AU - Moldovan, Dumitru

AU - Riedl, Marc A.

AU - Johnston, Douglas T.

AU - Li, Huamin

AU - Tang, Yongqiang

AU - Schranz, Jennifer

AU - Lu, Peng

AU - Vardi, Moshe

AU - Farkas, Henriette

AU - Keith, P.

AU - Yang, W.

AU - Maurer, M.

AU - Martinez-Saguer, I.

AU - Farkas, H.

AU - Reshef, A.

AU - Kivity, S.

AU - Moldovan, D.

AU - Caballero, T.

AU - Guilarte, M.

AU - Hernandez, M. D.

AU - González-Quevedo, M. T.

AU - Banerji, A.

AU - Bernstein, J.

AU - Bewtra, A.

AU - Craig, T.

AU - Fineman, S.

AU - Gower, R.

AU - Jacobs, J.

AU - Johnston, D.

AU - Kashkin, J.

AU - Li, H. H.

AU - Lumry, W. R.

AU - Manning, M.

AU - McNeil, D.

AU - Melamed, I.

AU - Mumneh, N.

AU - Nickel, T.

AU - Panuto, J.

AU - Soteres, D.

AU - Tachdjian, R.

AU - Offenberger, J.

AU - Wedner, J.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Fixed-dose

KW - Hereditary angioedema

KW - Liquid

KW - Long-term prophylactic treatment

KW - SAHARA study

KW - Subcutaneous

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U2 - 10.1016/j.jaip.2019.01.021

DO - 10.1016/j.jaip.2019.01.021

M3 - Article

VL - 7

SP - 1610-1618.e4

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

SN - 2213-2198

IS - 5

ER -