NCT00914966

A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE

Completed Phase 4 Results posted Last updated 23 June 2021

What this trial tests

Phase 4 trial testing C1 inhibitor (human) [C1 INH] in Hereditary Angioedema in 20 participants. Completed in 24 May 2012.

Timeline

31 August 2009

Primary endpoint
24 May 2012

24 May 2012

Quick facts

Lead sponsor	Shire
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	20
Start date	31 August 2009
Primary completion	24 May 2012
Estimated completion	24 May 2012
Sites	11 locations across United States

Drugs / interventions tested

• C1 inhibitor (human) [C1 INH] — full drug profile →

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.

Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance Primary · 12 to 24 weeks at each dose level

Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.

Adverse events

Group	Value	95% CI
Step 1: 1500 Units	15
Step 2: 2000 Units	11
Step 3: 2500 Units	11

Hospitalizations

Group	Value	95% CI
Step 1: 1500 Units	0
Step 2: 2000 Units	1
Step 3: 2500 Units	0

Systemic thrombotic events

Group	Value	95% CI
Step 1: 1500 Units	0
Step 2: 2000 Units	0
Step 3: 2500 Units	0

Local/catheter-related thrombotic events

Group	Value	95% CI
Step 1: 1500 Units	1
Step 2: 2000 Units	0
Step 3: 2500 Units	0

Treatment-emergent C1 INH antibodies

Group	Value	95% CI
Step 1: 1500 Units	0
Step 2: 2000 Units	0
Step 3: 2500 Units	1

Toxicity grade increases in laboratory parameters

Group	Value	95% CI
Step 1: 1500 Units	6
Step 2: 2000 Units	2
Step 3: 2500 Units	3

Potential clinically important vital signs changes

Group	Value	95% CI
Step 1: 1500 Units	3
Step 2: 2000 Units	1
Step 3: 2500 Units	1

Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates Secondary · 12 weeks at each dose level

Two definitions of success were applied in this study: 1) Per-protocol success - Average angioedema attack rate of ≤1.0 per month at the end of any dose escalation step (Week 12). The a priori definition of study success was 4 or more subjects with per-protocol success. 2) Investigator-determined success - Based on the investigator's clinical judgment, an average monthly angioedema attack rate demonstrating improvement sufficient for progression to follow-up. In addition, subjects who were not a per-protocol or investigator-determined success, but who experienced a reduction of \>1.0 attack pe

Per-protocol Success

Group	Value	95% CI
Step 1: 1500 Units	4
Step 2: 2000 Units	0
Step 3: 2500 Units	5

Investigator-determined Success

Group	Value	95% CI
Step 1: 1500 Units	1
Step 2: 2000 Units	0
Step 3: 2500 Units	1

Reduction of >1 attack/month from historical rate

Group	Value	95% CI
Step 1: 1500 Units	1
Step 2: 2000 Units	0
Step 3: 2500 Units	2

Non-responder

Group	Value	95% CI
Step 1: 1500 Units	1
Step 2: 2000 Units	1
Step 3: 2500 Units	4

Adverse events — posted to ClinicalTrials.gov

Time frame: 12 to 24 weeks at each dose level. Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Step 1: 1500 Units

Serious: 1/20 (5%)

Deaths: —

Step 2: 2000 Units

Serious: 1/13 (8%)

Deaths: —

Step 3: 2500 Units

Serious: 1/12 (8%)

Deaths: —

All Subjects

Serious: 2/20 (10%)

Deaths: —

Serious adverse events (4 terms)

Reaction	System	Step 1: 1500 Units	Step 2: 2000 Units	Step 3: 2500 Units	All Subjects
Anemia	Blood and lymphatic system disorders	—	—	—	—
Hereditary angioedema	Congenital, familial and genetic disorders	—	—	—	—
Bile duct stone	Hepatobiliary disorders	—	—	—	—
Cerebral hygroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—

Other adverse events (12 terms — click to expand)

Reaction	System	Step 1: 1500 Units	Step 2: 2000 Units	Step 3: 2500 Units	All Subjects
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Ligament sprain	Injury, poisoning and procedural complications	—	—	—	—
Medical device complication	General disorders	—	—	—	—
Peripheral edema	General disorders	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—
Rhinitis	Infections and infestations	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—

Most-reported serious reactions: Anemia, Hereditary angioedema, Bile duct stone, Cerebral hygroma.

Data from ClinicalTrials.gov NCT00914966 adverse events section.

Sponsor's own description

The objectives of the study were:

1. To assess the safety and tolerability of escalating doses of CINRYZE.
2. To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
3. To assess the immunogenicity of CINRYZE.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.