A Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema

NCT ID: NCT02316353

Last Updated: 2018-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2017-09-21

Brief Summary

The aim of this study is to assess the long-term safety of C1-esterase inhibitor (C1-INH) in preventing hereditary angioedema (HAE) attacks when it is administered under the skin of subjects with HAE. The safety of participating subjects will be assessed for up to 54 weeks. The long-term efficacy of C1-INH will also be assessed. Each eligible subject will enter the treatment phase, wherein subjects will be randomized to treatment with either low- or medium-volume C1-INH. Subjects who have an insufficient treatment response during the study will be given an opportunity to undergo a dose increase. The study aims to enroll eligible subjects who completed study CSL830_3001 (NCT01912456). Subjects who did not participate in study CSL830_3001 may also participate, if eligible and if space permits. Subjects from the United States (US) who complete Treatment Period 2 will be allowed to participate in an Extension Period. During the Extension Period participating US subjects will continue to receive treatment with open-label CSL830 for up to an additional 88 weeks.

Conditions

Hereditary Angioedema Types I and II

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

C1-INH - low-volume dose

A low-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period).

Group Type: EXPERIMENTAL

C1-esterase inhibitor

Intervention Type: BIOLOGICAL

C1-INH - medium-volume dose

A medium-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period).

Group Type: EXPERIMENTAL

C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Interventions

C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Males or females aged 6 years or older.
• A confirmed diagnosis of HAE type I or II.
• HAE attacks over a consecutive 2-month period that required acute treatment, medical attention, or caused significant functional impairment.
• For subjects who have used oral therapy for prophylaxis against HAE attacks within 3 months of first study visit: use of a stable regimen within 3 months of the first study visit.

Exclusion Criteria

• Incurable malignancies.
• Any clinical condition that will interfere with the evaluation of C1-INH therapy.
• Clinically significant history of poor response to C1-esterase therapy for the management of HAE.
• Suspected or confirmed diagnosis of acquired HAE or HAE with normal C1-INH.
• Inability to have HAE managed pharmacologically with on-demand treatment.

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Global Clinical Program Director

Role: STUDY_DIRECTOR

CSL Behring

Locations

Study Site

Birmingham, Alabama, United States

Study Site

Scottsdale, Arizona, United States

Study Site

La Jolla, California, United States

Study Site

Orange, California, United States

Study Site

Walnut Creek, California, United States

Study Site

Chevy Chase, Maryland, United States

Study Site

Cincinnati, Ohio, United States

Study Site

Tulsa, Oklahoma, United States

Study Site

Portland, Oregon, United States

Study Site

Hershey, Pennsylvania, United States

Study Site

Dallas, Texas, United States

Study Site

Richmond, Virginia, United States

Study Site

Campbelltown, New South Wales, Australia

Study Site

Hamilton, Ontario, Canada

Study Site

Ottawa, Ontario, Canada

Study Site

Toronto, Ontario, Canada

Study Site

Québec, , Canada

Study Site

Pilsen, , Czechia

Study Site

Mörfelden-Walldorf, Hesse, Germany

Study Site

Berlin, , Germany

Study Site

Frankfurt, , Germany

Study Site

Mainz, , Germany

Study Site

Budapest, , Hungary

Study Site

Tel Aviv, , Israel

Study Site

Tel Litwinsky, , Israel

Study Site

Catania, , Italy

Study Site

Milan, , Italy

Study Site

Cluj-Napoca, , Romania

Study Site

Madrid, , Spain

Study Site

Madrid, , Spain

Study Site

Valencia, , Spain

Study Site

London, , United Kingdom

Countries

United States; Australia; Canada; Czechia; Germany; Hungary; Israel; Italy; Romania; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36326435 (View on PubMed)

Lumry WR, Zuraw B, Cicardi M, Craig T, Anderson J, Banerji A, Bernstein JA, Caballero T, Farkas H, Gower RG, Keith PK, Levy DS, Li HH, Magerl M, Manning M, Riedl MA, Lawo JP, Prusty S, Machnig T, Longhurst H; on behalf of the COMPACT Investigators. Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study. Orphanet J Rare Dis. 2021 Feb 15;16(1):86. doi: 10.1186/s13023-020-01658-4.

Reference Type: DERIVED

PMID: 33588897 (View on PubMed)

Levy DS, Farkas H, Riedl MA, Hsu FI, Brooks JP, Cicardi M, Feuersenger H, Pragst I, Reshef A. Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial. Allergy Asthma Clin Immunol. 2020 Feb 4;16:8. doi: 10.1186/s13223-020-0409-3. eCollection 2020.

Reference Type: DERIVED

PMID: 32042283 (View on PubMed)

Craig T, Zuraw B, Longhurst H, Cicardi M, Bork K, Grattan C, Katelaris C, Sussman G, Keith PK, Yang W, Hebert J, Hanzlikova J, Staubach-Renz P, Martinez-Saguer I, Magerl M, Aygoren-Pursun E, Farkas H, Reshef A, Kivity S, Neri S, Crisan I, Caballero T, Baeza ML, Hernandez MD, Li H, Lumry W, Bernstein JA, Hussain I, Anderson J, Schwartz LB, Jacobs J, Manning M, Levy D, Riedl M, Christiansen S, Feuersenger H, Pragst I, Mycroft S, Pawaskar D, Jacobs I; COMPACT Investigators. Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1793-1802.e2. doi: 10.1016/j.jaip.2019.01.054. Epub 2019 Feb 15.

Reference Type: DERIVED

PMID: 30772477 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-001054-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSL830_3002

Identifier Type: -

Identifier Source: org_study_id