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

NCT02316353 | Completed Phase 3 Results

• 2 other identifiers: CSL830_30022014-001054-42
• Study Type: interventional
• Target: 126
• Locations: 11 countries
• Sites: 32

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

Outcome Measures

Primary Outcomes (2)

• Person-time Incidence Rates (Subject Based)

  Subject-based Analysis for Person-Time Incidence Rate = (the total number of subjects who experienced the event during the respective treatment) / (the sum of the date each subject experienced the event - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: the Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.

  Up to 146 weeks.

• The Person-time Incidence Rates (Event Based)

  Event-based Analysis for Person-Time Incidence Rate = (the total number of events documented during the respective treatment) / (the sum of each subject's end date - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830.

  Up to 146 weeks.

Secondary Outcomes (5)

• Percentage of Subjects Who Have Solicited Adverse Events (AEs)

  Up to 146 weeks

• Percentage of Injections Followed by At Least One Solicited Adverse Event

  Up to 146 weeks

• Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus.

  Up to 146 weeks

• Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period

  Up to 146 weeks

• Percentage of Subjects Who Are Responders

  Up to 146 weeks

Study Arms (2)

C1-INH - low-volume dose

EXPERIMENTAL

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).

Biological: C1-esterase inhibitor

C1-INH - medium-volume dose

EXPERIMENTAL

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).

Biological: C1-esterase inhibitor

Interventions

C1-esterase inhibitor BIOLOGICAL

C1-INH - low-volume dose; C1-INH - medium-volume dose

Eligibility Criteria

• Age: 6 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (32)

Study Site

Birmingham, Alabama, 35209, United States

Location

Study Site

Scottsdale, Arizona, 85251, United States

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Study Site

La Jolla, California, 92037, United States

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Study Site

Orange, California, 92868, United States

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Study Site

Walnut Creek, California, 94598, United States

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Study Site

Chevy Chase, Maryland, 20815, United States

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Study Site

Cincinnati, Ohio, 45231, United States

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Study Site

Tulsa, Oklahoma, 74136, United States

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Study Site

Portland, Oregon, 97223, United States

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Study Site

Hershey, Pennsylvania, 17033, United States

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Study Site

Dallas, Texas, 75231, United States

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Study Site

Richmond, Virginia, 23298, United States

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Study Site

Campbelltown, New South Wales, 2560, Australia

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Study Site

Hamilton, Ontario, L8N 3Z5, Canada

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Study Site

Ottawa, Ontario, K1Y 4G2, Canada

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Toronto, Ontario, M4V 1R2, Canada

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Québec, G1V 4M6, Canada

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Pilsen, 30460, Czechia

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Mörfelden-Walldorf, Hesse, 64546, Germany

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Berlin, 10117, Germany

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Frankfurt, 60596, Germany

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Mainz, 55131, Germany

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Budapest, 1125, Hungary

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Tel Aviv, 64239, Israel

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Tel Litwinsky, 52621, Israel

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Catania, 95123, Italy

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Milan, 20157, Italy

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Study Site

Cluj-Napoca, 400139, Romania

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Study Site

Madrid, 28007, Spain

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Study Site

Madrid, 28046, Spain

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Study Site

Valencia, 46026, Spain

Location

Study Site

London, E1 2ES, United Kingdom

Location

Related Publications (4)

• 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

• 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.

  PMID: 33588897 DERIVED

• 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.

  PMID: 32042283 DERIVED

• 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.

  PMID: 30772477 DERIVED

MeSH Terms

Conditions

Hereditary Angioedema Types I and II

Interventions

Complement C1 Inhibitor Protein

Condition Hierarchy (Ancestors)

Angioedemas, Hereditary; Angioedema; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Limitations and Caveats

None reported

Results Point of Contact

• Title: Michelle Hellstern
• Organization: CSL Behring

michelle.hellstern@cslbehring.com

6102907515

Study Officials

• Global Clinical Program Director

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2014
• First Posted: December 12, 2014
• Study Start: December 31, 2014
• Primary Completion: September 21, 2017
• Study Completion: September 21, 2017
• Last Updated: November 14, 2018
• Results First Posted: November 14, 2018

Record last verified: 2017-10

Locations

CZ (1); CA (4); IL (2); US (12); HU (1); IT (2); RO (1); GB (1); DE (4); ES (3); AU (1)