Safety of Ruconest in 2-13 Year Old Hereditary Angioedema (HAE) Patients

Study Overview
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Brief Summary
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This open-label study is being conducted to confirm the safety, pharmacokinetic profile and efficacy of Ruconest at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in patients, from 2 up to and including 13 years of age.

Detailed Description
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This study was an open-label, Phase 2, non-comparative, multinational, multicenter clinical study in pediatric patients from 2 up to and including 13 years of age, with a confirmed diagnosis of HAE. Patients were eligible for treatment with rhC1INH if they presented to the clinic within 5 hours of onset with an acute attack of at least moderate severity without signs of spontaneous regression. Patients received rhC1INH at a dose of 50 U/kg body weight up to a maximum of 4200 U. The reconstituted solution was administered as a slow intravenous (iv) injection over approximately 5 minutes. The patients remained in hospital and were closely monitored in the study center for at least 4 hours after study medication administration.

Official Title
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Open-label, Phase II, Single Arm Study to Evaluate the Safety, Immunogenicity, Pharmacokinetics and Efficacy of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Pediatric Patients With Hereditary Angioedema, From 2 up to and Including 13 Years of Age

Conditions
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Hereditary Angioedema

Intervention / Treatment
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* Drug: rhC1INH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: From 2 up to and including 13 years of age Clinical and laboratory confirmed diagnosis of HAE (baseline C1INH activity <50% of normal) Signed written informed consent (parental permission) signed by the legal guardian(s) Clinical symptoms of an acute HAE attack Onset of eligible symptoms within 5 hours from the moment at which medical evaluation to determine eligibility has occurred Attack severity moderate or greater, as rated by the investigator Exclusion Criteria: A diagnosis of acquired C1INH deficiency (AAE) A medical history of allergy to rabbits or rabbit-derived products or positive anti-rabbit epithelium (dander) IgE test

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 13 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Recombinant Human C1 Inhibitor<br>Patients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U. | Drug: rhC1INH<br>* Patients up to 84 kg will receive one i.v. injection of Ruconest at a dose of 50 U/kg. The reconstituted solution should be administered as a slow i.v. injection over approximately 5 minutes. Patients of 84 kg body weight or greater will receive one i.v. injection of Ruconest at the dose of 4200 U (2 vials).<br>* Other names: Ruconest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with Adverse Events | The safety and tolerability is assessed by the number of patients with at least one adverse event. | 90 Days | 
| Number of patients with positive neutralizing C1INH and rhC1INH specific antibody tests | Immunogenicity by assessing antibodies against rhC1INH (IgG and IgM) anti-rhC1INH | 90 Days | 
| Number of patients with confirmed host related impurities antibodies (Anti-HRI) after exposure to rhC1INH | Immunogenicity by assessing antibodies against host related impurities (anti-HRI) | 90 Days | 
| Number of patients with positive IgE against rabbit epithelium after exposure to rhC1INH with negative IgE test prior to exposure | Immunogenicity by assessing IgE antibodies against rabbit epithelium | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to beginning of relief | Time to beginning of relief assessed by using the overall severity visual analog scale(VAS), defined as the first time point with a decrease of at least 20 mm with respect to baseline at any eligible location, with persistence at the next time point | 24 Hours | 
| Time to minimal symptoms | Time to minimal symptoms assessed by using the overall severity VAS, defined as the first time point at which the overall severity VAS falls below 20 mm for each assessed location | 24 Hours | 
| Time to complete resolution | Patient-recorded time at which all angioedema symptoms at all locations have resolved | 28 Days (diary recording) | 
| Functional C1 Esterase Inhibitor activity 2-4 hours post dose | For pharmacokinetic profile the plasma functional C1INH activity was measured at presentation, 5 minutes post dose, and 2 to 4 hours post-dose for the first acute attack treated in the study. Functional C1INH concentrations are in units % of normal, i.e. results were expressed as a percentage based on a pool of plasma collected from healthy subjects, which was originally set on 100% | 4 Hours | 
| C4 concentration 2-4 hours post dose | For pharmacodynamic evaluation plasma C4 was measured at presentation, 5 minutes post-dose and 2 to 4 hours post-dose for the first attack treated in the study. | 4 Hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE, Hereditary Angioedema, Angioedema, Recombinant C1 Inhibitor, rhC1INH, Pediatrics