C1 Esterase Inhibitor (C1INH-nf) for the Treatment 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

NCT00289211

LEVP2005-1/Part A

Details and patient eligibility

About

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

Full description

Randomized subjects treated for a qualifying attack were eligible to receive rescue dosing with 1,000 U of C1INH-nf if they did not achieve beginning of substantial relief of the defining symptom within 4 hours after initial treatment with blinded study drug, or if at any time the attack progressed to include airway compromise. A second 1,000 U rescue dose was permitted 60 minutes after the initial rescue dose, if necessary.

The study design also allowed for administration of open-label C1INH-nf for laryngeal angioedema attacks, which were non-randomizable events due to the presence of or potential for airway compromise (immediate 1,000 U dose of C1INH-nf, repeated after 60 minutes, if necessary). In addition, subjects were eligible to receive open-label C1INH-nf (1,000 U single dose) prior to emergency surgical (non-cosmetic) procedures.

A total of 83 subjects were enrolled in the study. Seventy-one (71) subjects experienced qualifying attacks and were randomized to blinded study drug (36 C1INH-nf, 35 placebo); only the 71 randomized subjects were analyzed for efficacy. An additional 12 subjects were never randomized but received open-label C1INH-nf for treatment of laryngeal angioedema and/or prior to emergency surgical procedures. Of the 35 subjects randomized to placebo, 23 also received C1INH-nf (eg, rescue, open-label). In total, 83 subjects received at least 1 dose of study drug and were analyzed for safety; 71 subjects were exposed to C1INH-nf (59 randomized, 12 open-label only) and 12 subjects were exposed only to placebo.

Enrollment: 83 patients

Sex: All

Ages: 6+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented HAE
• Normal C1q level

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: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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83 participants in 2 patient groups, including a placebo group

C1INH-nf

Experimental group

Description:

1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.

Treatment:

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

Placebo

Placebo Comparator group

Description:

Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered.

Treatment:

Drug: Placebo (saline)