C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks

Shire

Status and phase: Completed; Phase 3

Conditions: Hereditary Angioedema

Treatments: Drug: Placebo (saline); Biological: C1 esterase inhibitor [human] (C1INH-nf)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01005888

LEVP2005-1/Part B

Details and patient eligibility

About

The study objective was to determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.

Full description

Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity).

The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures).

A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed to placebo.

Enrollment: 26 patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented HAE
• Normal C1q level
• Relatively frequent angioedema attacks (at least 2 per month on average)

Exclusion criteria

• Low C1q level
• B-cell malignancy
• Presence of anti-C1INH autoantibody
• History of allergic reaction to C1INH or other blood products
• Narcotic addiction
• Current participation in any other investigational drug study or within the past 30 days
• Participation in a C1 esterase inhibitor trial, or received blood or a blood product in the past 90 days
• Pregnancy or lactation
• Any clinically significant medical condition, such as renal failure, that in the opinion of the investigator would interfere with the subject's ability to participate in the study

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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26 participants in 2 patient groups

C1INH-nf First, then Placebo

Experimental group

Description:

1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks.

Treatment:

Drug: Placebo (saline)

Biological: C1 esterase inhibitor [human] (C1INH-nf)

Placebo First, then C1INH-nf

Experimental group

Description:

Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks.

Treatment:

Drug: Placebo (saline)

Biological: C1 esterase inhibitor [human] (C1INH-nf)