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

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ClinicalTrials.gov Identifier: NCT02316353
Recruitment Status : Completed
First Posted : December 12, 2014
Results First Posted : November 14, 2018
Last Update Posted : November 14, 2018
Sponsor:
Information provided by (Responsible Party):
CSL Behring

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.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema Types I and II Biological: C1-esterase inhibitor Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: An Open-label, Randomized Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneous Administration of Human Plasma-derived C1-esterase Inhibitor in the Prophylactic Treatment of Hereditary Angioedema
Actual Study Start Date : December 31, 2014
Actual Primary Completion Date : September 21, 2017
Actual Study Completion Date : September 21, 2017


Arm Intervention/treatment
Experimental: 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).
Biological: C1-esterase inhibitor
Experimental: 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).
Biological: C1-esterase inhibitor



Primary Outcome Measures :
  1. Person-time Incidence Rates (Subject Based) [ Time Frame: Up to 146 weeks. ]
    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.

  2. The Person-time Incidence Rates (Event Based) [ Time Frame: Up to 146 weeks. ]
    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.


Secondary Outcome Measures :
  1. Percentage of Subjects Who Have Solicited Adverse Events (AEs) [ Time Frame: Up to 146 weeks ]
    The number of subjects having at least 1 solicited local AE during a treatment were divided by the number of subjects in the corresponding treatment. 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.

  2. Percentage of Injections Followed by At Least One Solicited Adverse Event [ Time Frame: Up to 146 weeks ]
    The percent of injections followed by at least one solicited adverse event. 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. This was assessed across all participants, calculated as total number of events following injections / total number of injections across all participants, in each Arm.

  3. Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus. [ Time Frame: Up to 146 weeks ]
    Blood samples to be tested for HIV-1/-2, HBV, and HCV. 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.

  4. Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period [ Time Frame: Up to 146 weeks ]
    The percentage of subjects with a time-normalized merged HAE attack frequency of <1 HAE attack per 4-week period. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL 830.

  5. Percentage of Subjects Who Are Responders [ Time Frame: Up to 146 weeks ]
    A responder was defined as a subject with a ≥ 50% reduction in the time-normalized number of HAE attacks on CSL830 relative to the time-normalized number of HAE attacks used to qualify for participation in the current study. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830. Not all subjects in the ITT were available for this outcome measure.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02316353


  Show 32 Study Locations
Sponsors and Collaborators
CSL Behring
Investigators
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Study Director: Global Clinical Program Director CSL Behring
  Study Documents (Full-Text)

Documents provided by CSL Behring:
Study Protocol  [PDF] July 10, 2015
Statistical Analysis Plan  [PDF] September 12, 2017


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT02316353     History of Changes
Other Study ID Numbers: CSL830_3002
2014-001054-42 ( EudraCT Number )
First Posted: December 12, 2014    Key Record Dates
Results First Posted: November 14, 2018
Last Update Posted: November 14, 2018
Last Verified: October 2017
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Hereditary Angioedema Types I and II
Complement C1 Inhibitor Protein
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Genetic Diseases, Inborn
Complement C1s
Complement C1 Inactivator Proteins
Immunologic Factors
Physiological Effects of Drugs
Complement Inactivating Agents
Immunosuppressive Agents