Phase 3
N=90
A Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema
Hereditary Angioedema Types I and II
Bottom Line
View on ClinicalTrials.gov: NCT01912456 ↗Enrolled (actual)
90
Serious AEs
1.7%
Results posted
Jan 2021
Primary outcome: Primary: The Time-normalized Number of Hereditary Angioedema Attacks — 0.04; 0.02; 0.12; 0.13 attacks/day — p=< 0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Low-volume C1-esterase inhibitor (Biological); Higher-volume C1-esterase inhibitor (Biological); Low-volume placebo (Biological); Higher-volume placebo (Biological)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- CSL Behring
- Primary completion
- Oct 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Time-normalized Number of Hereditary Angioedema Attacks |
0.04; 0.02; 0.12; 0.13 | < 0.001 sig |
| SECONDARY Percentage of Subjects With a ≥ 50% Reduction in the Number of Hereditary Angioedema Attacks by CSL830 Treatment |
76.2; 90.0 | — |
| SECONDARY Time-Normalized Number of Uses of Rescue Medication |
0.04; 0.01; 0.18; 0.13 | < 0.001 sig |
| SECONDARY Percentage of Subjects With Adverse Events (AEs) Within 24 Hours of C1-esterase Inhibitor or Placebo Administration |
58.1; 60.5; 45.5; 54.8 | — |
| SECONDARY Percentage of Subjects With AEs or Other Specified Safety Events. |
67.4; 69.8; 61.4; 71.4 | — |
| SECONDARY Percentage of Subjects Experiencing Solicited AEs (Injection Site Reactions) |
27.9; 34.9; 22.7; 26.2 | — |
| SECONDARY Injections Resulting in Solicited AEs (Injection Site Reactions) |
0.21; 0.08; 0.12; 0.05 | — |
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.
Data sourced from ClinicalTrials.gov (NCT01912456). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.