search
Back to results

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

Primary Purpose

Hereditary Angioedema

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
rhC1INH
Sponsored by
Pharming Technologies B.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema focused on measuring Hereditary Angioedema, HAE, Angioedema, Recombinant C1 Inhibitor, rhC1INH, Pediatrics

Eligibility Criteria

2 Years - 13 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Portland Clinical Research/AAIM Care, LLC
  • UIA FN Plzen ( Institute of Immunology and Allergology), Faculty Hospital Plzen
  • University Hospital Motol, Institute of Immunology
  • Charité - Universitätsmedizin Berlin
  • Klinikum Rechts der Isar, Technical University Munich
  • Heim Pál Gyermekkórház, II. számú Gyermek Belgyógyászati Osztály
  • Bnei Zion Hospital
  • Sheba Medical Center
  • Souraski Medical Center
  • Hospital Luigi Sacco
  • Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona
  • University Clinic Of Dermatology Skopje
  • Pediatric Hospital
  • Pediatric Hospital
  • Mures County Clinical Hospital
  • Klinika detí a dorastu, Univerzitna nemocnica Martin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Recombinant Human C1 Inhibitor

Arm Description

Patients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U.

Outcomes

Primary Outcome Measures

Number of patients with Adverse Events
The safety and tolerability is assessed by the number of patients with at least one adverse event.
Number of patients with positive neutralizing C1INH and rhC1INH specific antibody tests
Immunogenicity by assessing antibodies against rhC1INH (IgG and IgM) anti-rhC1INH
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)
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

Secondary Outcome Measures

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
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
Time to complete resolution
Patient-recorded time at which all angioedema symptoms at all locations have resolved
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%
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.

Full Information

First Posted
May 19, 2011
Last Updated
July 13, 2018
Sponsor
Pharming Technologies B.V.
search

1. Study Identification

Unique Protocol Identification Number
NCT01359969
Brief Title
Safety of Ruconest in 2-13 Year Old Hereditary Angioedema (HAE) Patients
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
January 17, 2012 (Actual)
Primary Completion Date
July 17, 2017 (Actual)
Study Completion Date
July 17, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharming Technologies B.V.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema
Keywords
Hereditary Angioedema, HAE, Angioedema, Recombinant C1 Inhibitor, rhC1INH, Pediatrics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Recombinant Human C1 Inhibitor
Arm Type
Experimental
Arm Description
Patients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U.
Intervention Type
Drug
Intervention Name(s)
rhC1INH
Other Intervention Name(s)
Ruconest
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of patients with Adverse Events
Description
The safety and tolerability is assessed by the number of patients with at least one adverse event.
Time Frame
90 Days
Title
Number of patients with positive neutralizing C1INH and rhC1INH specific antibody tests
Description
Immunogenicity by assessing antibodies against rhC1INH (IgG and IgM) anti-rhC1INH
Time Frame
90 Days
Title
Number of patients with confirmed host related impurities antibodies (Anti-HRI) after exposure to rhC1INH
Description
Immunogenicity by assessing antibodies against host related impurities (anti-HRI)
Time Frame
90 Days
Title
Number of patients with positive IgE against rabbit epithelium after exposure to rhC1INH with negative IgE test prior to exposure
Description
Immunogenicity by assessing IgE antibodies against rabbit epithelium
Time Frame
28 Days
Secondary Outcome Measure Information:
Title
Time to beginning of relief
Description
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
Time Frame
24 Hours
Title
Time to minimal symptoms
Description
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
Time Frame
24 Hours
Title
Time to complete resolution
Description
Patient-recorded time at which all angioedema symptoms at all locations have resolved
Time Frame
28 Days (diary recording)
Title
Functional C1 Esterase Inhibitor activity 2-4 hours post dose
Description
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%
Time Frame
4 Hours
Title
C4 concentration 2-4 hours post dose
Description
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.
Time Frame
4 Hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Portland Clinical Research/AAIM Care, LLC
City
Portland
State/Province
Oregon
ZIP/Postal Code
97015
Country
United States
Facility Name
UIA FN Plzen ( Institute of Immunology and Allergology), Faculty Hospital Plzen
City
Plzen
State/Province
Alej Svobody 80
ZIP/Postal Code
304 60 Plzen
Country
Czechia
Facility Name
University Hospital Motol, Institute of Immunology
City
Prague
State/Province
V Úvalu 84
ZIP/Postal Code
150 06 Prague
Country
Czechia
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
State/Province
Charitéplatz 1
ZIP/Postal Code
10117
Country
Germany
Facility Name
Klinikum Rechts der Isar, Technical University Munich
City
Munich
Country
Germany
Facility Name
Heim Pál Gyermekkórház, II. számú Gyermek Belgyógyászati Osztály
City
Budapest
State/Province
Madarász Utca 22-24
ZIP/Postal Code
1131
Country
Hungary
Facility Name
Bnei Zion Hospital
City
Haifa
Country
Israel
Facility Name
Sheba Medical Center
City
Tel Hashomer
Country
Israel
Facility Name
Souraski Medical Center
City
Tel-Aviv
Country
Israel
Facility Name
Hospital Luigi Sacco
City
Milan
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona
City
Salerno
ZIP/Postal Code
84131
Country
Italy
Facility Name
University Clinic Of Dermatology Skopje
City
Skopje
ZIP/Postal Code
1000
Country
Macedonia, The Former Yugoslav Republic of
Facility Name
Pediatric Hospital
City
Krakow
Country
Poland
Facility Name
Pediatric Hospital
City
Lublin
Country
Poland
Facility Name
Mures County Clinical Hospital
City
Targu Mures
Country
Romania
Facility Name
Klinika detí a dorastu, Univerzitna nemocnica Martin
City
Martin
State/Province
Kollárova 2
ZIP/Postal Code
036 59 Martin
Country
Slovakia

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs