Safety and Efficacy Study of CINRYZE for Prevention of Angioedema Attacks in Children Ages 6-11 With Hereditary Angioedema

NCT02052141 | Completed Phase 3 Results

• 3 other identifiers: 0624-3012013-002453-29SHP616-301
• Study Type: interventional
• Target: 12
• Locations: 5 countries
• Sites: 8

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.

Conditions

Hereditary Angioedema (HAE)

Keywords

Pediatric; C1 inhibitor; HAE; Cinryze; C1 INH; Prevention

Outcome Measures

Primary Outcomes (1)

• Normalized Number of Angioedema Attacks Per Month in a Treatment Period

  Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.

  From start of treatment up to 12 weeks during each treatment period

Secondary Outcomes (8)

• Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period

  From start of treatment up to 12 weeks during each treatment period

• Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period

  From start of treatment up to 12 weeks during each intervention period

• Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a Treatment Period

  From start of treatment up to 12 weeks during each intervention period

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group

  From start of study treatment up to 25 weeks

• Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen

  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

Study Arms (2)

500/1000

EXPERIMENTAL

500 Units of CINRYZE administered by IV injection twice per week for 12 weeks followed by 1000 Units of CINRYZE administered by IV injection twice per week for 12 weeks

Biological: CINRYZE 500; Biological: CINRYZE 1000

1000/500

EXPERIMENTAL

1000 Units of CINRYZE administered by IV injection twice per week for 12 weeks followed by 500 Units of CINRYZE administered by IV injection twice per week for 12 weeks

Biological: CINRYZE 500; Biological: CINRYZE 1000

Interventions

CINRYZE 500 BIOLOGICAL

500 Units of CINRYZE administered by IV injection

1000/500; 500/1000

CINRYZE 1000 BIOLOGICAL

1000 Units of CINRYZE administered by IV injection

1000/500; 500/1000

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (8)

Asthma and Allergy Associates, P.C

Colorado Springs, Colorado, 80907, United States

Location

Nevada Access to Research and Education Society

Las Vegas, Nevada, 89106, United States

Location

Oregon Allergy Associates

Eugene, Oregon, 97401, United States

Location

Klinikum der J.W. Goethe Universitat

Frankfurt, 60590, Germany

Location

HZRM Hamophilie Zentrum Rhein Main GmbH

Mörfelden-Walldorf, 64546, Germany

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Instituto Nacional de Pediatria

Mexico City, 04530, Mexico

Location

Clinical County Hospital Mures

Târgu Mureş, 540072, Romania

Location

Related Publications (3)

• 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.

  PMID: 28662509 RESULT

• 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.

  PMID: 36326435 DERIVED

• 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.

  PMID: 30968444 DERIVED

MeSH Terms

Conditions

Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Immunologic Deficiency Syndromes

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2014
• First Posted: January 31, 2014
• Study Start: March 20, 2014
• Primary Completion: May 4, 2017
• Study Completion: May 4, 2017
• Last Updated: June 3, 2021
• Results First Posted: August 28, 2018

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

IL (1); ME (1); US (3); DE (2); RO (1)