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

CSL Behring

Status and phase: Completed; Phase 3

Conditions: Hereditary Angioedema Types I and II

Treatments: Biological: Low-volume C1-esterase inhibitor; Biological: Low-volume placebo; Biological: Higher-volume placebo; Biological: Higher-volume C1-esterase inhibitor

Study type: Interventional

Funder types: Industry

Identifiers

NCT01912456

2013-000916-10 (EudraCT Number)

CSL830_3001

Details and patient eligibility

About

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.

Enrollment: 90 patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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90 participants in 4 patient groups

Higher-volume placebo, then low-volume C1-esterase inhibitor

Experimental group

Description:

A higher-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks, then a low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks.

Treatment:

Biological: Low-volume C1-esterase inhibitor

Biological: Higher-volume placebo

Low-volume C1-esterase inhibitor, then higher-volume placebo

Experimental group

Description:

A low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks, then a higher-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks.

Treatment:

Biological: Low-volume C1-esterase inhibitor

Biological: Higher-volume placebo

Low-volume placebo, then higher-volume C1-esterase inhibitor

Experimental group

Description:

A low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks then a higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks.

Treatment:

Biological: Higher-volume C1-esterase inhibitor

Biological: Low-volume placebo

Higher-volume C1-esterase inhibitor, then low-volume placebo

Experimental group

Description:

A higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks, then a low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks.

Treatment:

Biological: Higher-volume C1-esterase inhibitor

Biological: Low-volume placebo