Clinical trial NCT02052141: Safety and Efficacy Study of CINRYZE for Prevention of Angioedema Attacks in Children Ages 6-11 With Hereditary Angioedema
Official title: A Phase 3, Multicenter, Randomized, Single-Blind, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of Intravenous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) for the Prevention of Angioedema Attacks in Children 6 to 11 Years of Age With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Keywords: Pediatric
C1 inhibitor
HAE
Cinryze
C1 INH
Prevention
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-01-31
Enrollment: 12
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Primary Objective - To assess the relative efficacy of two dose levels of CINRYZE (500 Units and 1000 Units) administered by intravenous (IV) injection every 3 or 4 days to prevent angioedema attacks in children 6 to 11 years of age with hereditary angioedema (HAE).

Secondary Objectives - To assess the safety and tolerability, characterize the pharmacokinetics (PK) and pharmacodynamics (PD), and assess the immunogenicity of two dose levels of CINRYZE administered by IV injection in children 6 to 11 years of age with HAE.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of Type I or Type II HAE.
* History of angioedema attacks.

Exclusion Criteria:

* History of bleeding or clotting abnormality.
* Diagnosis of acquired angioedema or known to have C1 INH antibodies.
* History of allergic reaction to C1 esterase inhibitor or other blood products.
* Receipt of any experimental agents other than those required for prevention or treatment of angioedema attacks within 30 days prior to screening.

Primary outcomes:
measure: Normalized Number of Angioedema Attacks Per Month in a Treatment Period
timeFrame: From start of treatment up to 12 weeks during each treatment period
Secondary outcomes:
measure: Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period
timeFrame: From start of treatment up to 12 weeks during each treatment period
measure: Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period
timeFrame: From start of treatment up to 12 weeks during each intervention period
measure: Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a Treatment Period
timeFrame: From start of treatment up to 12 weeks during each intervention period
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group
timeFrame: From start of study treatment up to 25 weeks
measure: Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen
timeFrame: Pre-dose and 1 hour (h) post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
measure: C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma
timeFrame: Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
measure: Plasma Concentration of Complement C4
timeFrame: Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
measure: Number of Participants With C1 Esterase Inhibitor (C1 INH) Antibodies in Plasma
timeFrame: Pre-dose, 1 week post treatment (Week 13, Week 25) and 1 month post treatment follow-up (Week 28)
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates, P.C
state: Colorado
city: Las Vegas
country: United States
facility: Nevada Access to Research and Education Society
state: Nevada
city: Eugene
country: United States
facility: Oregon Allergy Associates
state: Oregon
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitat
city: Mörfelden-Walldorf
country: Germany
facility: HZRM Hamophilie Zentrum Rhein Main GmbH
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Mexico City
country: Mexico
facility: Instituto Nacional de Pediatria
city: Targu-Mures
country: Romania
facility: Clinical County Hospital Mures
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Aygoren-Pursun E, Soteres D, Moldovan D, Christensen J, Van Leerberghe A, Hao J, Schranz J, Jacobson KW, Martinez-Saguer I. Preventing Hereditary Angioedema Attacks in Children Using Cinryze(R): Interim Efficacy and Safety Phase 3 Findings. Int Arch Allergy Immunol. 2017;173(2):114-119. doi: 10.1159/000477541. Epub 2017 Jun 30.
citation: Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
citation: Aygoren-Pursun E, Soteres DF, Nieto-Martinez SA, Christensen J, Jacobson KW, Moldovan D, Van Leerberghe A, Tang Y, Lu P, Vardi M, Schranz J, Martinez-Saguer I. A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema. Pediatr Allergy Immunol. 2019 Aug;30(5):553-561. doi: 10.1111/pai.13060. Epub 2019 May 29.