Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: Phase 3, randomized, placebo-controlled trial

Marc A. Riedl, Jonathan A. Bernstein, Huamin Li, Avner Reshef, William Lumry, Dumitru Moldovan, Henriette Farkas, Robyn Levy, James Baker, Yun Hardiman, Mark C. Totoritis, Anurag Relan, Marco Cicardi

Research output: Contribution to journalArticle

Abstract

Background Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. Objective To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. Methods Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. Results Median (95% confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P =.031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P =.003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P =.078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P =.005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. Conclusion Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.

Original languageEnglish (US)
JournalAnnals of Allergy, Asthma and Immunology
Volume112
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

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Complement C1 Inhibitor Protein
Hereditary Angioedemas
Randomized Controlled Trials
Placebos
Visual Analog Scale
Safety
Therapeutics
Anaphylaxis
human SERPING1 protein
Neutralizing Antibodies
Confidence Intervals
Surveys and Questionnaires

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pulmonary and Respiratory Medicine

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Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks : Phase 3, randomized, placebo-controlled trial. / Riedl, Marc A.; Bernstein, Jonathan A.; Li, Huamin; Reshef, Avner; Lumry, William; Moldovan, Dumitru; Farkas, Henriette; Levy, Robyn; Baker, James; Hardiman, Yun; Totoritis, Mark C.; Relan, Anurag; Cicardi, Marco.

In: Annals of Allergy, Asthma and Immunology, Vol. 112, No. 2, 02.2014.

Research output: Contribution to journalArticle

Riedl, MA, Bernstein, JA, Li, H, Reshef, A, Lumry, W, Moldovan, D, Farkas, H, Levy, R, Baker, J, Hardiman, Y, Totoritis, MC, Relan, A & Cicardi, M 2014, 'Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: Phase 3, randomized, placebo-controlled trial', Annals of Allergy, Asthma and Immunology, vol. 112, no. 2. https://doi.org/10.1016/j.anai.2013.12.004
Riedl, Marc A. ; Bernstein, Jonathan A. ; Li, Huamin ; Reshef, Avner ; Lumry, William ; Moldovan, Dumitru ; Farkas, Henriette ; Levy, Robyn ; Baker, James ; Hardiman, Yun ; Totoritis, Mark C. ; Relan, Anurag ; Cicardi, Marco. / Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks : Phase 3, randomized, placebo-controlled trial. In: Annals of Allergy, Asthma and Immunology. 2014 ; Vol. 112, No. 2.
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abstract = "Background Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. Objective To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. Methods Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. Results Median (95{\%} confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P =.031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P =.003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P =.078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P =.005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. Conclusion Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.",
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T2 - Phase 3, randomized, placebo-controlled trial

AU - Riedl, Marc A.

AU - Bernstein, Jonathan A.

AU - Li, Huamin

AU - Reshef, Avner

AU - Lumry, William

AU - Moldovan, Dumitru

AU - Farkas, Henriette

AU - Levy, Robyn

AU - Baker, James

AU - Hardiman, Yun

AU - Totoritis, Mark C.

AU - Relan, Anurag

AU - Cicardi, Marco

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N2 - Background Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. Objective To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. Methods Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. Results Median (95% confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P =.031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P =.003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P =.078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P =.005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. Conclusion Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.

AB - Background Hereditary angioedema (HAE), caused by C1 inhibitor (C1INH) deficiency or dysfunction, is characterized by recurrent attacks of tissue swelling affecting multiple anatomic locations. Recombinant human C1INH (rhC1INH) has been shown effective for acute treatment of HAE attacks. Objective To evaluate the efficacy and safety of rhC1INH (50 IU/kg to maximum 4,200 IU/treatment) vs placebo in a larger HAE population. Methods Seventy-five patients experiencing peripheral, abdominal, facial, and/or oropharyngeal laryngeal attacks were randomized (3:2) to rhC1INH (n = 44) or placebo (saline; n = 31). Efficacy was assessed by patient responses on a Treatment Effect Questionnaire (TEQ) and visual analog scale (VAS). Safety also was evaluated. Results Median (95% confidence interval) time to beginning of symptom relief at the primary attack location was 90 minutes (61-150) in rhC1INH-treated patients vs 152 minutes (93, not estimable) in placebo-treated patients (P =.031) based on the TEQ and 75 minutes (60-105) vs 303 minutes (81-720, P =.003) based on a VAS decrease of at least 20 mm. Median time to minimal symptoms was 303 minutes (240-720) in rhC1INH-treated patients vs 483 minutes (300-1,440) in placebo-treated patients based on the TEQ (P =.078) and 240 minutes (177-270) vs 362 minutes (240, not estimable; P =.005), based on an overall VAS less than 20 mm. Overall, rhC1INH was safe and well tolerated; no thromboembolic events, anaphylaxis, or neutralizing antibodies were observed. Conclusion Relief of symptoms of HAE attacks was achieved faster with rhC1INH compared with placebo as assessed by the TEQ and VAS, with a positive safety profile. Results are consistent with previous studies showing efficacy and safety of rhC1INH in patients with HAE.

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