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

NCT ID: NCT01912456

Last Updated: 2021-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-10-31

Brief Summary

The aim of this study is to assess the efficacy of C1-esterase inhibitor in preventing hereditary angioedema attacks when it is administered under the skin of subjects with hereditary angioedema. The safety of C1-esterase inhibitor will also be assessed. Each subject will enter a run-in period of up to 8-weeks. Subjects who complete the run-in period and who are eligible will then enter the treatment phase which comprises two sequential treatment periods. In the treatment phase, subjects will be randomized to one of four arms consisting of treatment with low- or higher-volume C1-esterase inhibitor in one treatment period and treatment with low- or higher-volume placebo in the other treatment period. The study will measure the number of hereditary angioedema attacks that subjects experience while receiving each treatment.

Conditions

Hereditary Angioedema Types I and II

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Higher-volume placebo, then low-volume C1-esterase inhibitor

A higher-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks, then a low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks.

Group Type: EXPERIMENTAL

Low-volume C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Higher-volume placebo

Intervention Type: BIOLOGICAL

Low-volume C1-esterase inhibitor, then higher-volume placebo

A low-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks, then a higher-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks.

Group Type: EXPERIMENTAL

Low-volume C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Higher-volume placebo

Intervention Type: BIOLOGICAL

Low-volume placebo, then higher-volume C1-esterase inhibitor

A low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks then a higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks.

Group Type: EXPERIMENTAL

Higher-volume C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Low-volume placebo

Intervention Type: BIOLOGICAL

Higher-volume C1-esterase inhibitor, then low-volume placebo

A higher-volume dose of C1-esterase inhibitor will be administered subcutaneously twice a week for up to 16 weeks, then a low-volume dose of placebo will be administered subcutaneously twice a week for up to 16 weeks.

Group Type: EXPERIMENTAL

Higher-volume C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Low-volume placebo

Intervention Type: BIOLOGICAL

Interventions

Low-volume C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Higher-volume C1-esterase inhibitor

Intervention Type: BIOLOGICAL

Low-volume placebo

Intervention Type: BIOLOGICAL

Higher-volume placebo

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Males or females aged 12 years or older.
• A clinical diagnosis of hereditary angioedema type I or II.
• Hereditary angioedema 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 Screening: use of a stable regimen within 3 months of Screening, with no plans to change.

Eligibility Criteria for Entering Treatment Period 1:

• Laboratory confirmation of type I or type II hereditary angioedema, including C1-esterase inhibitor functional activity less than 50% AND C4 antigen level below the laboratory reference range.
• No clinically significant abnormalities as assessed using laboratory parameters.
• During participation in the run-in period, subjects must have experienced hereditary angioedema attacks that required acute treatment, required medical attention, or caused significant functional impairment.

Exclusion Criteria

• History of clinical significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.
• Incurable malignancies at screening.
• Any clinical condition that will interfere with the evaluation of C1-esterase inhibitor therapy.
• Clinically significant history of poor response to C1-esterase therapy for the management of hereditary angioedema.
• Receiving therapy prohibited by the protocol, including medications for hereditary angioedema prophylaxis.
• Female subjects who started taking or changed dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progesterone-containing products) within 3 months prior to the screening visit.

• Minimum Eligible Age: 12 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

Valencia, , Spain

Study Site

Brighton, , United Kingdom

Study Site

London, , United Kingdom

Study Site

Birmingham, Alabama, United States

Study Site

Scottsdale, Arizona, United States

Study Site

Bell Gardens, California, United States

Study Site

La Jolla, California, United States

Study Site

Orange, California, United States

Study Site

Walnut Creek, California, United States

Study Site

Colorado Springs, Colorado, United States

Study Site

Chevy Chase, Maryland, United States

Study Site

Boston, Massachusetts, United States

Study Site

Cincinnati, Ohio, United States

Study Site

Columbus, Ohio, United States

Study Site

Toledo, Ohio, United States

Study Site

Tulsa, Oklahoma, United States

Study Site

Lake Oswego, Oregon, United States

Study Site

Hershey, Pennsylvania, United States

Study Site

Dallas, Texas, United States

Study Site

Richmond, Virginia, United States

Study Site

Virginia Beach, Virginia, United States

Study Site

Spokane, Washington, 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

Hradec Králové, , Czechia

Study Site

Pilsen, , Czechia

Study Site

Budapest, , Hungary

Study Site

Tel Aviv, , Israel

Study Site

Tel Litwinsky, , Israel

Study Site

Catania, , Italy

Study Site

Palermo, , Italy

Study Site

Cluj-Napoca, , Romania

Study Site

Mures, , Romania

Study Site

Barcelona, , Spain

Study Site

Madrid, , Spain

Study Site

Madrid, , Spain

Countries

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

References

Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, Li HH, Reshef A, Bonner J, Bernstein JA, Anderson J, Lumry WR, Farkas H, Katelaris CH, Sussman GL, Jacobs J, Riedl M, Manning ME, Hebert J, Keith PK, Kivity S, Neri S, Levy DS, Baeza ML, Nathan R, Schwartz LB, Caballero T, Yang W, Crisan I, Hernandez MD, Hussain I, Tarzi M, Ritchie B, Kralickova P, Guilarte M, Rehman SM, Banerji A, Gower RG, Bensen-Kennedy D, Edelman J, Feuersenger H, Lawo JP, Machnig T, Pawaskar D, Pragst I, Zuraw BL; COMPACT Investigators. Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. N Engl J Med. 2017 Mar 23;376(12):1131-1140. doi: 10.1056/NEJMoa1613627.

Reference Type: RESULT

PMID: 28328347 (View on PubMed)

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)

Li HH, Zuraw B, Longhurst HJ, Cicardi M, Bork K, Baker J, Lumry W, Bernstein J, Manning M, Levy D, Riedl MA, Feuersenger H, Prusty S, Pragst I, Machnig T, Craig T; COMPACT Investigators. Subcutaneous C1 inhibitor for prevention of attacks of hereditary angioedema: additional outcomes and subgroup analysis of a placebo-controlled randomized study. Allergy Asthma Clin Immunol. 2019 Aug 28;15:49. doi: 10.1186/s13223-019-0362-1. eCollection 2019.

Reference Type: DERIVED

PMID: 31485239 (View on PubMed)

Other Identifiers

2013-000916-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CSL830_3001

Identifier Type: -

Identifier Source: org_study_id