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

NCT01912456 | Completed Phase 3 Results

• 2 other identifiers: CSL830_30012013-000916-10
• Study Type: interventional
• Target: 90
• Locations: 10 countries
• Sites: 39

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

Keywords

Hereditary Angioedema

Outcome Measures

Primary Outcomes (1)

• The Time-normalized Number of Hereditary Angioedema Attacks

  The time normalized number of HAE attacks as reported by the investigator per subject was calculated as: The total number of HAE attacks per subject and per treatment period / length of stay of subject in treatment period (days), Where length of stay of subject in treatment period was calculated as: Date of last day of subject in treatment period - date of first day of Week 3 of subject in treatment period + 1.

  During the treatment phase, up to 28 weeks.

Secondary Outcomes (6)

• Percentage of Subjects With a ≥ 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment

  During the treatment phase, up to 28 weeks.

• Time-Normalized Number of Uses of Rescue Medication

  During the treatment phase, up to 28 weeks.

• Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration

  Within 24 hours of C1-esterase inhibitor or placebo administration.

• Percentage of Subjects With AEs or Other Specified Safety Events.

  During the treatment phase, up to 32 weeks.

• Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions)

  During the treatment phase, up to 32 weeks.

Study Arms (4)

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

EXPERIMENTAL

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.

Biological: Low-volume C1-esterase inhibitor; Biological: Higher-volume placebo

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

EXPERIMENTAL

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.

Biological: Low-volume C1-esterase inhibitor; Biological: Higher-volume placebo

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

EXPERIMENTAL

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.

Biological: Higher-volume C1-esterase inhibitor; Biological: Low-volume placebo

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

EXPERIMENTAL

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.

Biological: Higher-volume C1-esterase inhibitor; Biological: Low-volume placebo

Interventions

Low-volume C1-esterase inhibitor BIOLOGICAL

Higher-volume placebo, then low-volume C1-esterase inhibitor; Low-volume C1-esterase inhibitor, then higher-volume placebo

Higher-volume C1-esterase inhibitor BIOLOGICAL

Higher-volume C1-esterase inhibitor, then low-volume placebo; Low-volume placebo, then higher-volume C1-esterase inhibitor

Low-volume placebo BIOLOGICAL

Higher-volume C1-esterase inhibitor, then low-volume placebo; Low-volume placebo, then higher-volume C1-esterase inhibitor

Higher-volume placebo BIOLOGICAL

Higher-volume placebo, then low-volume C1-esterase inhibitor; Low-volume C1-esterase inhibitor, then higher-volume placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (39)

Study Site

Birmingham, Alabama, 35209, United States

Location

Study Site

Scottsdale, Arizona, 85251, United States

Location

Study Site

Bell Gardens, California, 90201, United States

Location

Study Site

La Jolla, California, 92093, United States

Location

Study Site

Orange, California, 92868, United States

Location

Study Site

Walnut Creek, California, 94598, United States

Location

Study Site

Colorado Springs, Colorado, 80907, United States

Location

Study Site

Chevy Chase, Maryland, 20815, United States

Location

Study Site

Boston, Massachusetts, 02114, United States

Location

Study Site

Cincinnati, Ohio, 45267-0563, United States

Location

Study Site

Columbus, Ohio, 43235, United States

Location

Study Site

Toledo, Ohio, 43617, United States

Location

Study Site

Tulsa, Oklahoma, 74136, United States

Location

Study Site

Lake Oswego, Oregon, 97035, United States

Location

Study Site

Hershey, Pennsylvania, 17033, United States

Location

Study Site

Dallas, Texas, 75231, United States

Location

Study Site

Richmond, Virginia, 23298, United States

Location

Study Site

Virginia Beach, Virginia, 23452, United States

Location

Study Site

Spokane, Washington, 99204, United States

Location

Study Site

Campbelltown, New South Wales, 2560, Australia

Location

Study Site

Hamilton, Ontario, L8N 3Z5, Canada

Location

Study Site

Ottawa, Ontario, K1Y 4G2, Canada

Location

Study Site

Toronto, Ontario, M4V 1R2, Canada

Location

Study Site

Québec, G1V 4M6, Canada

Location

Study Site

Hradec Králové, 50005, Czechia

Location

Study Site

Pilsen, 30460, Czechia

Location

Study Site

Budapest, 1125, Hungary

Location

Study Site

Tel Aviv, 64239, Israel

Location

Study Site

Tel Litwinsky, 52621, Israel

Location

Study Site

Catania, 95123, Italy

Location

Study Site

Palermo, 90146, Italy

Location

Study Site

Cluj-Napoca, 400139, Romania

Location

Study Site

Mures, 540103, Romania

Location

Study Site

Barcelona, 08035, Spain

Location

Study Site

Madrid, 28007, Spain

Location

Study Site

Madrid, 28046, Spain

Location

Study Site

Valencia, 46026, Spain

Location

Study Site

Brighton, BN2 5BE, United Kingdom

Location

Study Site

London, E1 2ES, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 28328347 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

• 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.

  PMID: 31485239 DERIVED

MeSH Terms

Conditions

Hereditary Angioedema Types I and II; Angioedemas, Hereditary

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: CSL Behring GmbH

clinicaltrials@cslbehring.com

610-878-4000

Study Officials

• Global Clinical Program Director

  CSL Behring

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2013
• First Posted: July 31, 2013
• Study Start: January 1, 2014
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: January 29, 2021
• Results First Posted: January 29, 2021

Record last verified: 2021-01

Locations

GB (2); IL (2); US (19); CA (4); CZ (2); IT (2); HU (1); RO (2); AU (1); ES (4)