Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Trial record 2 of 56 for:    "Hereditary angioedema"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by CSL Behring
Sponsor:
Information provided by (Responsible Party):
CSL Behring
ClinicalTrials.gov Identifier:
NCT01912456
First received: July 29, 2013
Last updated: October 6, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Hereditary Angioedema Types I and II
Biological: Low-volume C1-esterase inhibitor
Biological: Higher-volume C1-esterase inhibitor
Biological: Low-volume placebo
Biological: Higher-volume placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-blind, Randomized, Placebo-controlled, Cross-over Study to Evaluate the Clinical Efficacy and Safety of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema

Resource links provided by NLM:


Further study details as provided by CSL Behring:

Primary Outcome Measures:
  • The time-normalized number of hereditary angioedema attacks [ Time Frame: During the treatment phase, up to 32 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of subjects with a ≥ 50% reduction in the number of hereditary angioedema attacks [ Time Frame: During the treatment phase, up to 32 weeks. ] [ Designated as safety issue: No ]
    The percentage of subjects with a ≥ 50% relative reduction in the time-normalized number of hereditary angioedema attacks during treatment with C1-esterase inhibitor compared with placebo

  • Number of uses of rescue medication [ Time Frame: During the treatment phase, up to 32 weeks. ] [ Designated as safety issue: No ]
    The time-normalized number of uses of rescue medication during treatment with C1-esterase inhibitor or placebo

  • Percentage of subjects with adverse events (AEs). [ Time Frame: Within 24 hours of C1-esterase inhibitor or placebo administration. ] [ Designated as safety issue: Yes ]
  • Percentage of subjects with AEs or other specified safety events. [ Time Frame: During the treatment phase, up to 32 weeks. ] [ Designated as safety issue: Yes ]
    The percentage of subjects with unsolicited AEs, serious AEs, or other specified safety events during treatment with C1-esterase inhibitor or placebo.

  • Percentage of subjects experiencing solicited AEs [ Time Frame: During the treatment phase, up to 32 weeks. ] [ Designated as safety issue: Yes ]
    The percentage of subjects experiencing solicited AEs (injection site reactions) during treatment with C1-esterase inhibitor or placebo.

  • Percentage of investigational product injections resulting in solicited AEs [ Time Frame: During the treatment phase, up to 32 weeks. ] [ Designated as safety issue: Yes ]
    The percentage of injections of C1-esterase inhibitor or placebo that result in solicited AEs (injection site reactions).


Estimated Enrollment: 80
Study Start Date: January 2014
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: Low-volume C1-esterase inhibitor Biological: Higher-volume placebo
Experimental: 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.
Biological: Low-volume C1-esterase inhibitor Biological: Higher-volume placebo
Experimental: 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.
Biological: Higher-volume C1-esterase inhibitor Biological: Low-volume placebo
Experimental: 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.
Biological: Higher-volume C1-esterase inhibitor Biological: Low-volume placebo

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Run-In Period 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:

Run-In Period 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01912456

Contacts
Contact: Clinical Trials Registration Coordinator clinicaltrials@cslbehring.com

  Show 38 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
Study Director: Global Clinical Program Director CSL Behring
  More Information

No publications provided

Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT01912456     History of Changes
Other Study ID Numbers: CSL830_3001, 2013-000916-10
Study First Received: July 29, 2013
Last Updated: October 6, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Canada: Institutional Review Board
Israel: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Romania: National Agency for Medicines and Medical Devices
Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
Czech Republic: State Institute for Drug Control
Italy: The Italian Medicines Agency

Keywords provided by CSL Behring:
Hereditary Angioedema

Additional relevant MeSH terms:
Angioedemas, Hereditary
Hereditary Angioedema Types I and II
Angioedema
Cardiovascular Diseases
Genetic Diseases, Inborn
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Vascular
Urticaria
Vascular Diseases
Complement C1 Inactivator Proteins
Complement C1 Inhibitor Protein
Complement C1s
Complement Inactivating Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014