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

Hereditary Angioedema Clinical Trial

Official title:

Open-label, Phase II, Single Arm Study to Evaluate the Safety, Immunogenicity, Pharmacokinetics and Efficacy of rhC1INH for the Treatment of Acute Attacks in Pediatric Patients With Hereditary Angioedema, From 2-13 Years of Age

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359969
• Other study ID #: C1 1209
• Secondary ID: 2011-000987-92
• Status: Completed
• Phase: Phase 2
• Start date: January 17, 2012
• Est. completion date: July 17, 2017

Study information

• Verified date: March 2024
• Source: Pharming Technologies B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 recombinant human C1-inhibitor (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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: July 17, 2017
• Est. primary completion date: July 17, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 13 Years

Eligibility

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 Form (ICF)(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) immunoglobuline E (IgE) test

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema

Intervention

Drug:
• rhC1INH
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).

Locations

Country	Name	City	State
Czechia	UIA FN Plzen ( Institute of Immunology and Allergology), Faculty Hospital Plzen	Plzen	Alej Svobody 80
Czechia	University Hospital Motol, Institute of Immunology	Prague	V Úvalu 84
Germany	Charité - Universitätsmedizin Berlin	Berlin	Charitéplatz 1
Germany	Klinikum Rechts der Isar, Technical University Munich	Munich
Hungary	Heim Pál Gyermekkórház, II. számú Gyermek Belgyógyászati Osztály	Budapest	Madarász Utca 22-24
Israel	Bnei Zion Hospital	Haifa
Israel	Sheba Medical Center	Tel Hashomer
Israel	Souraski Medical Center	Tel-Aviv
Italy	Hospital Luigi Sacco	Milan
Italy	Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona	Salerno
North Macedonia	University Clinic Of Dermatology Skopje	Skopje
Poland	Pediatric Hospital	Krakow
Poland	Pediatric Hospital	Lublin
Romania	Mures County Clinical Hospital	Targu Mures
Slovakia	Klinika detí a dorastu, Univerzitna nemocnica Martin	Martin	Kollárova 2
United States	Portland Clinical Research/AAIM Care, LLC	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Pharming Technologies B.V.

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Hungary,  Israel,  Italy,  North Macedonia,  Poland,  Romania,  Slovakia, 

References & Publications (1)

Reshef A, Grivcheva-Panovska V, Kessel A, Kivity S, Klimaszewska-Rembiasz M, Moldovan D, Farkas H, Gutova V, Fritz S, Relan A, Giannetti B, Magerl M. Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children. Pediatr — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Beginning of Relief Based on Visual Analogue Scale (VAS) Was Defined as the Time, in Minutes, From Time of Infusion to the Beginning of Relief.	Time to beginning of relief of symptoms that showed the response to treatment based on the overall VAS score decrease of = 20 mm from baseline. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the oro-pharyngeal-laryngeal (OPL) VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination. Time to beginning of relief will also be calculated based on the Investigator Score (IS) and Treatment Effect Questionnaire (TEQ).	The assessment of the angioedema signs by the VAS and TEQ will be performed just before start of infusion, and at T30m, T1h, T2h, T4h, T8h and T24h after study medication infusion VAS score decrease of = 20 mm from baseline.
Secondary	Time to Minimal Symptoms Based on Patient's VAS Scores; Time From the Start of the Infusion of Study Medication to the First Assessment Time at Which the Overall Severity VAS Reaches a Value of Less Than 20 mm for All Locations	Time to minimal symptoms was defined as the time at which the Overall VAS score fell below 20 mm for all locations where VAS Scores were recorded. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines provided to answer each question related to the severity of symptoms and the patient's condition. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the OPL VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination.	The assessment of the angioedema signs by the VAS and TEQ will be performed just before start of infusion, and at T30m, T1h, T2h, T4h, T8h and T24h after study medication infusion all locations where VAS Scores were recorded.