Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks

Study Overview
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Brief Summary
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HAE is a rare disorder characterized by functional C1 esterase inhibitor deficiency. If not treated adequately, the acute attacks of HAE can be life-threatening and may even result in fatalities, especially in case of swelling of the larynx. This clinical Phase 2/Phase 3 study was designed to provide clinically relevant data on dosing, efficacy and safety in subjects with HAE.

Detailed Description
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For each subject, only a single abdominal or facial attack was treated and evaluated. After receiving treatment, subjects were observed for a minimum of 4 hours, after which they could be discharged from the study center if they reported onset of symptom relief. Starting from 4 hours after treatment, subjects who reported insufficient or no symptom relief could receive a second dose of double-blind treatment (called rescue medication) as follows: C1-INH 20 U/kg bw for subjects initially receiving placebo, C1-INH 10 U/kg bw for subjects initially receiving C1-INH 10 U/kg bw, and placebo for subjects initially receiving C1-INH 20 U/kg bw. The study was defined to be successful if the primary outcome measure and at least one of the secondary outcome measures were met in the comparison between the C1-INH 20 U/kg bw group and the Placebo group.

Official Title
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Human Pasteurized C1 Esterase Inhibitor Concentrate (CE1145) in Subjects With Congenital C1-INH Deficiency and Acute Abdominal or Facial HAE Attacks

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Biological: C1 Esterase Inhibitor
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented congenital C1-INH deficiency Acute facial or abdominal HAE attack Key Exclusion Criteria: Acquired angioedema Treatment with any other investigational drug within the last 30 days before study entry Treatment with any C1-INH concentrate within the previous 7 days

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C1-INH 10 U/kg bw<br>10 Units (U)/kg body weight (bw) dose | Biological: C1 Esterase Inhibitor<br>* Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min.<br>* Other names: CE1145;|
| Experimental: C1-INH 20 U/kg bw<br>20 U/kg bw dose | Biological: C1 Esterase Inhibitor<br>* Single application of C1-INH administered intravenously by slow injection or infusion at a recommended rate of 4mL/min.<br>* Other names: CE1145;|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Single application of physiological saline solution equivalent to the volume calculated for subjects in the C1-INH 20 U/kg bw arm.<br>* Other names: Physiological saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Start of Relief of Symptoms From HAE Attack | The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief. | Up to 24 h after start of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Worsened Intensity of Clinical HAE Symptoms | Includes any worsening of intensity of at least 1 of the HAE symptoms present at baseline. Routinely checked symptoms included pain, nausea, vomiting, cramps, and diarrhea. | Baseline and between 2 and 4 h after start of study treatment | 
| Number of Vomiting Episodes |  | Within 4 h after start of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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C1 Inhibitor, Hereditary angioedema, Acute HAE attack