NCT00289211

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

Completed Phase 3 Results posted Last updated 11 June 2021

What this trial tests

Phase 3 trial testing C1 esterase inhibitor [human] (C1INH-nf) in Hereditary Angioedema in 83 participants. Completed in 13 April 2007.

Timeline

14 March 2005

Primary endpoint
13 April 2007

13 April 2007

Quick facts

Lead sponsor	Shire
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	83
Start date	14 March 2005
Primary completion	13 April 2007
Estimated completion	13 April 2007
Sites	37 locations across United States

Drugs / interventions tested

• C1 esterase inhibitor [human] (C1INH-nf) — full drug profile →
• Placebo (saline)

Conditions studied

• Hereditary Angioedema — all drugs for Hereditary Angioedema →

Sponsor

Shire — full company profile →

Who can join

6 and older, any sex, with Hereditary Angioedema. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Beginning of Substantial Relief of the Defining Symptom Primary · Within 4 hours after initial treatment

Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.

Group	Value	95% CI
C1INH-nf	2.0	1.0 – 4.0
Placebo	4.0	2.0 – 4.0

Number of Subjects With Beginning of Substantial Relief of the Defining Symptom Secondary · Within 4 hours after initial treatment

Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.

Group	Value	95% CI
C1INH-nf	21
Placebo	14

Time to Complete Resolution of the HAE Attack Secondary · 72 hours

Randomized subjects were contacted 72-96 hours (3-4 days) after discharge from the study site to determine when complete resolution of the HAE attack occurred.

Group	Value	95% CI
C1INH-nf	12.3	10.1 – 18.0
Placebo	31.6	17.8 – 46.0

Antigenic C1 Inhibitor (C1INH) Serum Levels Secondary · Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion

Change in antigenic C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.

Pre-infusion (N=34, N=33)

Group	Value	95% CI
C1INH-nf	14.7	± 22.21
Placebo	13.0	± 16.42

Change at 1 hour post-infusion (N=35, N=32)

Group	Value	95% CI
C1INH-nf	6.7	± 8.86
Placebo	-0.9	± 9.25

Change at 2 hours post-infusion (N=23, N=27)

Group	Value	95% CI
C1INH-nf	11.7	± 12.86
Placebo	0.5	± 6.73

Change at 4 hours post-infusion (N=28, N=23)

Group	Value	95% CI
C1INH-nf	8.6	± 8.92
Placebo	0.4	± 6.72

Change at 12 hours post-infusion (N=19, N=13)

Group	Value	95% CI
C1INH-nf	5.6	± 11.21
Placebo	-0.8	± 4.39

Functional C1INH Serum Levels Secondary · Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion

Percent change in functional C1INH serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH).

Pre-infusion (N=34, N=31)

Group	Value	95% CI
C1INH-nf	35.6	± 22.62
Placebo	33.7	± 29.04

Percent change 1 hour post-infusion (N=35, N=32)

Group	Value	95% CI
C1INH-nf	31.5	± 23.94
Placebo	-6.4	± 23.73

Percent change 2 hours post-infusion (N=23, N=26)

Group	Value	95% CI
C1INH-nf	45.6	± 23.70
Placebo	1.0	± 12.43

Percent change 4 hours post-infusion (N=28, N=25)

Group	Value	95% CI
C1INH-nf	34.5	± 28.22
Placebo	4.3	± 26.02

Percent change 12 hours post-infusion (N=19, N=14)

Group	Value	95% CI
C1INH-nf	34.8	± 17.24
Placebo	5.1	± 32.09

Complement C4 Serum Levels Secondary · Pre-infusion to 1-, 2-, 4-, and 12 hours post-infusion

Change in complement C4 serum levels from pre-infusion to 1-, 2-, 4-, and 12 hours after the initial dose of blinded study drug.

Pre-infusion (N=35, N=32)

Group	Value	95% CI
C1INH-nf	8.1	± 7.79
Placebo	6.7	± 5.32

Change at 1 hour post-infusion (N=33, N=30)

Group	Value	95% CI
C1INH-nf	-0.7	± 5.59
Placebo	-0.9	± 1.96

Change at 2 hours post-infusion (N=21, N=26)

Group	Value	95% CI
C1INH-nf	-1.7	± 8.12
Placebo	-1.1	± 2.13

Change at 4 hours post-infusion (N=26, N=22)

Group	Value	95% CI
C1INH-nf	-1.0	± 5.62
Placebo	-0.5	± 1.90

Change at 12 hours post-infusion (N=19, N=14)

Group	Value	95% CI
C1INH-nf	2.9	± 6.33
Placebo	0.1	± 2.07

Adverse events — posted to ClinicalTrials.gov

Time frame: 3 months. As the study design allowed for all subjects (even those randomized to placebo) to receive C1INH-nf, safety data are presented by actual treatment received (C1INH-nf 71, placebo 12), not randomized treatment group (see Detailed Description).. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

C1INH-nf

Serious: 0/71 (0%)

Deaths: —

Placebo

Serious: 0/12 (0%)

Deaths: —

Other adverse events (3 terms — click to expand)

Reaction	System	C1INH-nf	Placebo
Dermatitis contact	Skin and subcutaneous tissue disorders	—	—
Injection site rash	General disorders	—	—
Tetany	Metabolism and nutrition disorders	—	—

Data from ClinicalTrials.gov NCT00289211 adverse events section.

Sponsor's own description

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

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema.
   Zuraw BL, Busse PJ, White M, Jacobs J, et al · · 2010 · cited 280× · PMID 20818886 · DOI 10.1056/nejmoa0805538