Open-label study to evaluate the safety, 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

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2011-000987-92-IT
• Date of registration: 27/12/2011
• Prospective Registration: Yes
• Primary sponsor: PHARMING TECHNOLOGIES B.V.
• Public title: Open-label study to evaluate the safety, 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
• Scientific 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
• Date of first enrolment: 27/12/2011
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000987-92
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Germany, Hungary, Israel, Italy, Slovakia

Contacts

• Name: Wim Vermeulen
• Affiliation: Pharming Technologies B.V.

• Name: Wim Vermeulen
• Affiliation: Pharming Technologies B.V.

Key inclusion & exclusion criteria

Inclusion criteria:
Screening • 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) Treatment • 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 • IS score for at least one anatomical location at the time of initial evaluation of at least 3 (moderate severity or greater) without signs of spontaneous regression • 24h or more have passed since the patient’s last study treatment
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Screening
? A diagnosis of acquired C1INH deficiency (AAE)
? A medical history of allergy to rabbits or rabbit-derived products (including rhC1INH, antisera),
or positive anti-rabbit epithelium (dander) IgE test (cut off>0.35 kU/L in ImmunoCap assay
(Phadia, Sweden) or equivalent)
? Treatment with investigational drug in another clinical study in the last 30 days
? Any clinical significant abnormality in the physical examination and/or the routine laboratory
assessments, that in the opinion of the Investigator makes the patient unsuitable for
participation in the study
? Patient or legal guardian whose decision to participate might be unduly influenced by
perceived expectation of gain or harm by participation, such as patient or legal guardian in
detention due to official or legal order
? Any condition or treatment that in the opinion of the investigator might interfere with the
evaluation of the study objectives
Treatment
? Any changes since screening that would exclude patient based on above exclusion criteria.
? 10 HAE attacks were previously treated with study medication.
? Suspicion for an alternate explanation of the symptoms other than an acute HAE attack.
? Use of any disallowed concomitant medication since onset of acute HAE attack (see Section
8.2.1).
? Positive pregnancy test (urine or serum)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Hereditary angioedema (HAE). Hereditary angioedema is characterized by angioedema localized and recurrent caused by by uncontrolled activation of the Complement systems due to congenital deficiency of Functional C1 inhibitor (C1INH). Reports in Medical the literature suggests that C1INH replacement therapy with human plasma-derived represents a safe and effective acute attacks of HA
MedDRA version: 14.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Trade Name: Ruconest
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: conestat alfa
Current Sponsor code: rhC1INH
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 2100-

Primary Outcome(s)

Primary end point(s): The primary objective is Safety Tolllerability and immunogenicity. Safety and tolerability by standard criteria (vital signs, ECG, adverse events, routine laboratory safety parameters and immunogenicity (anti-host related impurities (HRI) and anti C1INH antibodies)

Secondary Objective: - to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of Ruconest in the treatment of acute angioedema attacks in 2-13 year old HAE patients to assess the efficacy of Ruconest in the treatment of acute angioedema attacks in 2-13 year old HAE patientsu

Timepoint(s) of evaluation of this end point: AEs will be recorded throughout the study. For safety evaluation, prior to and at Day 28 after study medication administration, a blood sample will be drawn for routine laboratory parameters. In addition to monitoring of vital signs (prior to and 30 min, 1, 2 and 4 hours after study medication administration), an ECG will be recorded prior to and between 30 minutes and 2 hours after study medication administration.

Main Objective: to assess the clinical safety, immunogenicity and tolerability of Ruconest in the treatment of acute angioedema attacks in 2-13 year old HAE patients

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For PK/PD evaluation, blood samples will be collected prior to the first treated attack, and at 5 minutes and between 2 and 4 hours following the first study medication administration. For Efficacy evaluation: The evolution of the acute angioedema attack will be monitored by the administration of patient questionnaires (Visual Analog Scale (VAS) and Treatment Effect Questionnaire (TEQ)) at 30 min, 1, 2, 4, 8, and 24 hours, and the Investigator Score (IS) at 30 min, 1, 2 and 4 hours post study medication administration.

Secondary end point(s): To assess the pharmacokinetics (PK) and pharmacodynamics (PD) of Ruconest in the treatment of acute angioedema attacks in 2-13 year old HAE patients. To assess the efficacy of Ruconest in the treatment of acute angioedema attacks in 2-13 year old HAE patients.

Secondary ID(s)

2011-000987-92-DE

C11209

Source(s) of Monetary Support

PHARMING TECHNOLOGIES B.V.