Clinical trial NCT02316353: A Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Official title: An Open-label, Randomized Study to Evaluate the Long-term Clinical Safety and Efficacy 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
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2014-12-12
Enrollment: 126
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to assess the long-term safety of C1-esterase inhibitor (C1-INH) in preventing hereditary angioedema (HAE) attacks when it is administered under the skin of subjects with HAE. The safety of participating subjects will be assessed for up to 54 weeks. The long-term efficacy of C1-INH will also be assessed. Each eligible subject will enter the treatment phase, wherein subjects will be randomized to treatment with either low- or medium-volume C1-INH. Subjects who have an insufficient treatment response during the study will be given an opportunity to undergo a dose increase. The study aims to enroll eligible subjects who completed study CSL830_3001 (NCT01912456). Subjects who did not participate in study CSL830_3001 may also participate, if eligible and if space permits. Subjects from the United States (US) who complete Treatment Period 2 will be allowed to participate in an Extension Period. During the Extension Period participating US subjects will continue to receive treatment with open-label CSL830 for up to an additional 88 weeks.


Eligibility criteria: Inclusion Criteria:

* Males or females aged 6 years or older.
* A confirmed diagnosis of HAE type I or II.
* HAE 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 first study visit: use of a stable regimen within 3 months of the first study visit.

Exclusion Criteria:

* Incurable malignancies.
* Any clinical condition that will interfere with the evaluation of C1-INH therapy.
* Clinically significant history of poor response to C1-esterase therapy for the management of HAE.
* Suspected or confirmed diagnosis of acquired HAE or HAE with normal C1-INH.
* Inability to have HAE managed pharmacologically with on-demand treatment.

Primary outcomes:
measure: Person-time Incidence Rates (Subject Based)
timeFrame: Up to 146 weeks.
measure: The Person-time Incidence Rates (Event Based)
timeFrame: Up to 146 weeks.
Secondary outcomes:
measure: Percentage of Subjects Who Have Solicited Adverse Events (AEs)
timeFrame: Up to 146 weeks
measure: Percentage of Injections Followed by At Least One Solicited Adverse Event
timeFrame: Up to 146 weeks
measure: Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus.
timeFrame: Up to 146 weeks
measure: Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period
timeFrame: Up to 146 weeks
measure: Percentage of Subjects Who Are Responders
timeFrame: Up to 146 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: 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: Chevy Chase
country: United States
facility: Study Site
state: Maryland
city: Cincinnati
country: United States
facility: Study Site
state: Ohio
city: Tulsa
country: United States
facility: Study Site
state: Oklahoma
city: Portland
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: 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: Plzen
country: Czechia
facility: Study Site
city: Mörfelden-Walldorf
country: Germany
facility: Study Site
state: Hesse
city: Berlin
country: Germany
facility: Study Site
city: Frankfurt
country: Germany
facility: Study Site
city: Mainz
country: Germany
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: Milano
country: Italy
facility: Study Site
city: Cluj Napoca
country: Romania
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: London
country: United Kingdom
facility: Study Site
Study officials:
affiliation: CSL Behring
name: Global Clinical Program Director
role: STUDY_DIRECTOR
References:
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: Lumry WR, Zuraw B, Cicardi M, Craig T, Anderson J, Banerji A, Bernstein JA, Caballero T, Farkas H, Gower RG, Keith PK, Levy DS, Li HH, Magerl M, Manning M, Riedl MA, Lawo JP, Prusty S, Machnig T, Longhurst H; on behalf of the COMPACT Investigators. Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study. Orphanet J Rare Dis. 2021 Feb 15;16(1):86. doi: 10.1186/s13023-020-01658-4.
citation: Levy DS, Farkas H, Riedl MA, Hsu FI, Brooks JP, Cicardi M, Feuersenger H, Pragst I, Reshef A. Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial. Allergy Asthma Clin Immunol. 2020 Feb 4;16:8. doi: 10.1186/s13223-020-0409-3. eCollection 2020.
citation: Craig T, Zuraw B, Longhurst H, Cicardi M, Bork K, Grattan C, Katelaris C, Sussman G, Keith PK, Yang W, Hebert J, Hanzlikova J, Staubach-Renz P, Martinez-Saguer I, Magerl M, Aygoren-Pursun E, Farkas H, Reshef A, Kivity S, Neri S, Crisan I, Caballero T, Baeza ML, Hernandez MD, Li H, Lumry W, Bernstein JA, Hussain I, Anderson J, Schwartz LB, Jacobs J, Manning M, Levy D, Riedl M, Christiansen S, Feuersenger H, Pragst I, Mycroft S, Pawaskar D, Jacobs I; COMPACT Investigators. Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1793-1802.e2. doi: 10.1016/j.jaip.2019.01.054. Epub 2019 Feb 15.