A Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema

Phase 3

Completed

• Conditions: Hereditary Angioedema Types I and II
• Interventions: Biological: C1-esterase inhibitor

• Registration Number: NCT02316353
• Lead Sponsor: CSL Behring

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-12-10
• Study First Submitted QC: 2014-12-10
• Study First Posted: 2014-12-12
• Study Start: 2014-12-31
• Primary Completion: 2017-09-21
• Study Completion: 2017-09-21
• Status Verified: 2017-10
• Results First Submitted: 2018-09-18
• Results First Submitted QC: 2018-10-17
• Last Update Submitted: 2018-10-17
• Results First Posted: 2018-11-14
• Last Update Posted: 2018-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 126

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
C1-INH - medium-volume dose	C1-esterase inhibitor	A medium-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period).
C1-INH - low-volume dose	C1-esterase inhibitor	A low-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period).

Primary Outcome Measures

Name	Time	Method
Person-time Incidence Rates (Subject Based)	Up to 146 weeks.	Subject-based Analysis for Person-Time Incidence Rate = (the total number of subjects who experienced the event during the respective treatment) / (the sum of the date each subject experienced the event - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: the Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
The Person-time Incidence Rates (Event Based)	Up to 146 weeks.	Event-based Analysis for Person-Time Incidence Rate = (the total number of events documented during the respective treatment) / (the sum of each subject's end date - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.

Secondary Outcome Measures

Name	Time	Method
Percentage of Injections Followed by At Least One Solicited Adverse Event	Up to 146 weeks	The percent of injections followed by at least one solicited adverse event. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. This was assessed across all participants, calculated as total number of events following injections / total number of injections across all participants, in each Arm.
Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period	Up to 146 weeks	The percentage of subjects with a time-normalized merged HAE attack frequency of \<1 HAE attack per 4-week period. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL 830.
Percentage of Subjects Who Are Responders	Up to 146 weeks	A responder was defined as a subject with a ≥ 50% reduction in the time-normalized number of HAE attacks on CSL830 relative to the time-normalized number of HAE attacks used to qualify for participation in the current study. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830. Not all subjects in the ITT were available for this outcome measure.
Percentage of Subjects Who Have Solicited Adverse Events (AEs)	Up to 146 weeks	The number of subjects having at least 1 solicited local AE during a treatment were divided by the number of subjects in the corresponding treatment. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.
Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus.	Up to 146 weeks	Blood samples to be tested for HIV-1/-2, HBV, and HCV. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.

Trial Locations

Locations (1)

Study Site; 🇬🇧 London, United Kingdom