A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Condition: Hereditary Angioedema Types I and II
MeSH terms: Angioedema; Angioedemas, Hereditary; Hereditary Angioedema Types I and II
Intervention: Low-volume C1-esterase inhibitor; Higher-volume C1-esterase inhibitor; Low-volume placebo; Higher-volume placebo
Intervention MeSH terms: Complement C1s; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Hereditary Angioedema

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.
    

Eligibility 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.