Clinical trial NCT01912456: A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Official title: A Double-blind, Randomized, Placebo-controlled, Cross-over Study to Evaluate the Clinical Efficacy and Safety of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema Types I and II
Keywords: Hereditary Angioedema
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2013-07-31
Enrollment: 90
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The aim of this study is to assess the efficacy of C1-esterase inhibitor in preventing hereditary angioedema attacks when it is administered under the skin of subjects with hereditary angioedema. The safety of C1-esterase inhibitor will also be assessed. Each subject will enter a run-in period of up to 8-weeks. Subjects who complete the run-in period and who are eligible will then enter the treatment phase which comprises two sequential treatment periods. In the treatment phase, subjects will be randomized to one of four arms consisting of treatment with low- or higher-volume C1-esterase inhibitor in one treatment period and treatment with low- or higher-volume placebo in the other treatment period. The study will measure the number of hereditary angioedema attacks that subjects experience while receiving each treatment.


Eligibility criteria: Inclusion Criteria:

Run-In Period Inclusion Criteria:

* Males or females aged 12 years or older.
* A clinical diagnosis of hereditary angioedema type I or II.
* Hereditary angioedema attacks over a consecutive 2-month period that required acute treatment, medical attention, or caused significant functional impairment.
* For subjects who have used oral therapy for prophylaxis against HAE attacks within 3 months of Screening: use of a stable regimen within 3 months of Screening, with no plans to change.

Eligibility Criteria for Entering Treatment Period 1:

* Laboratory confirmation of type I or type II hereditary angioedema, including C1-esterase inhibitor functional activity less than 50% AND C4 antigen level below the laboratory reference range.
* No clinically significant abnormalities as assessed using laboratory parameters.
* During participation in the run-in period, subjects must have experienced hereditary angioedema attacks that required acute treatment, required medical attention, or caused significant functional impairment.

Exclusion Criteria:

Run-In Period Exclusion Criteria:

* History of clinical significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.
* Incurable malignancies at screening.
* Any clinical condition that will interfere with the evaluation of C1-esterase inhibitor therapy.
* Clinically significant history of poor response to C1-esterase therapy for the management of hereditary angioedema.
* Receiving therapy prohibited by the protocol, including medications for hereditary angioedema prophylaxis.
* Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progesterone-containing products) within 3 months prior to the screening visit.

Primary outcomes:
measure: The Time-normalized Number of Hereditary Angioedema Attacks
timeFrame: During the treatment phase, up to 28 weeks.
Secondary outcomes:
measure: Percentage of Subjects With a ≥ 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment
timeFrame: During the treatment phase, up to 28 weeks.
measure: Time-Normalized Number of Uses of Rescue Medication
timeFrame: During the treatment phase, up to 28 weeks.
measure: Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration
timeFrame: Within 24 hours of C1-esterase inhibitor or placebo administration.
measure: Percentage of Subjects With AEs or Other Specified Safety Events.
timeFrame: During the treatment phase, up to 32 weeks.
measure: Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions)
timeFrame: During the treatment phase, up to 32 weeks.
measure: Injections Resulting in Solicited AEs (Injection Site Reactions)
timeFrame: During the treatment phase, up to 32 weeks.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Study Site
state: Alabama
city: Scottsdale
country: United States
facility: Study Site
state: Arizona
city: Bell Gardens
country: United States
facility: Study Site
state: California
city: La Jolla
country: United States
facility: Study Site
state: California
city: Orange
country: United States
facility: Study Site
state: California
city: Walnut Creek
country: United States
facility: Study Site
state: California
city: Colorado Springs
country: United States
facility: Study Site
state: Colorado
city: Chevy Chase
country: United States
facility: Study Site
state: Maryland
city: Boston
country: United States
facility: Study Site
state: Massachusetts
city: Cincinnati
country: United States
facility: Study Site
state: Ohio
city: Columbus
country: United States
facility: Study Site
state: Ohio
city: Toledo
country: United States
facility: Study Site
state: Ohio
city: Tulsa
country: United States
facility: Study Site
state: Oklahoma
city: Lake Oswego
country: United States
facility: Study Site
state: Oregon
city: Hershey
country: United States
facility: Study Site
state: Pennsylvania
city: Dallas
country: United States
facility: Study Site
state: Texas
city: Richmond
country: United States
facility: Study Site
state: Virginia
city: Virginia Beach
country: United States
facility: Study Site
state: Virginia
city: Spokane
country: United States
facility: Study Site
state: Washington
city: Campbelltown
country: Australia
facility: Study Site
state: New South Wales
city: Hamilton
country: Canada
facility: Study Site
state: Ontario
city: Ottawa
country: Canada
facility: Study Site
state: Ontario
city: Toronto
country: Canada
facility: Study Site
state: Ontario
city: Quebec
country: Canada
facility: Study Site
city: Hradec Kralove
country: Czechia
facility: Study Site
city: Plzen
country: Czechia
facility: Study Site
city: Budapest
country: Hungary
facility: Study Site
city: Tel Aviv
country: Israel
facility: Study Site
city: Tel Hashomer
country: Israel
facility: Study Site
city: Catania
country: Italy
facility: Study Site
city: Palermo
country: Italy
facility: Study Site
city: Cluj Napoca
country: Romania
facility: Study Site
city: Mures
country: Romania
facility: Study Site
city: Barcelona
country: Spain
facility: Study Site
city: Madrid
country: Spain
facility: Study Site
city: Madrid
country: Spain
facility: Study Site
city: Valencia
country: Spain
facility: Study Site
city: Brighton
country: United Kingdom
facility: Study Site
city: London
country: United Kingdom
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Global Clinical Program Director
role: STUDY_DIRECTOR
References:
citation: Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, Li HH, Reshef A, Bonner J, Bernstein JA, Anderson J, Lumry WR, Farkas H, Katelaris CH, Sussman GL, Jacobs J, Riedl M, Manning ME, Hebert J, Keith PK, Kivity S, Neri S, Levy DS, Baeza ML, Nathan R, Schwartz LB, Caballero T, Yang W, Crisan I, Hernandez MD, Hussain I, Tarzi M, Ritchie B, Kralickova P, Guilarte M, Rehman SM, Banerji A, Gower RG, Bensen-Kennedy D, Edelman J, Feuersenger H, Lawo JP, Machnig T, Pawaskar D, Pragst I, Zuraw BL; COMPACT Investigators. Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. N Engl J Med. 2017 Mar 23;376(12):1131-1140. doi: 10.1056/NEJMoa1613627.
citation: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
citation: Li HH, Zuraw B, Longhurst HJ, Cicardi M, Bork K, Baker J, Lumry W, Bernstein J, Manning M, Levy D, Riedl MA, Feuersenger H, Prusty S, Pragst I, Machnig T, Craig T; COMPACT Investigators. Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study. Allergy Asthma Clin Immunol. 2019 Aug 28;15:49. doi: 10.1186/s13223-019-0362-1. eCollection 2019.