Hereditary Angioedema
Conditions
Keywords
HAE, Hereditary Angioedema, Prophylaxis
Brief summary
Primary Objective: To evaluate the efficacy of recombinant human C1 inhibitor (rhC1INH) in the prophylaxis of angioedema attacks in patients with HAE Secondary Objective: To evaluate the safety and immunogenicity of recombinant human C1 inhibitor (rhC1INH) in the prophylaxis of angioedema attacks in patients with HAE
Detailed description
Study Design: This is a multi-center, randomized, double-blind, placebo-controlled, 3-period crossover study of rhC1INH in prophylaxis of angioedema attacks in patients with HAE. Medical screening (clinical and laboratory parameters) will be performed and patient medical history specific to HAE attacks will be collected to assess eligibility. Each patient will receive three 4 week periods of treatment twice weekly.
Interventions
BIOLOGICALRecombinant human C1 inhibitor
OTHERPlacebo
Sponsors
Pharming Technologies B.V.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients fulfilling the following criteria at Screening are eligible for participation in the study: 1. Age 13 years or older 2. Laboratory confirmed diagnosis of HAE 3. A history of frequent HAE attacks (at least 4 attacks per month across a minimum of 3 consecutive months). 4. Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception. 5. Provided written informed consent (and written assent for minors) 6. Willingness and ability to comply with all protocol procedures
Exclusion criteria
Patients who meet any of the following criteria at Screening are to be excluded from study participation: 1. Patients with medical history of allergy to rabbits or rabbit-derived products (including rhC1INH) 2. Diagnosis of acquired angioedema (AAE) 3. Patients who are pregnant, or breastfeeding, or are currently intending to become pregnant 4. Treatment with any investigational drug in the past 30 days 5. Patients with any condition or treatment that, in the opinion of the Investigator, might interfere with the evaluation of study objectives 6. Patients currently treated with angiotensin-converting enzyme (ACE) inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of HAE Attacks | 28 days | Average number of HAE attacks normalized to a 28 day period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | 20 weeks | Number of participants that experienced Treatment Emergent Adverse Events observed in safety population |
| Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks | 28 days | Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity | 20 weeks | Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies |
Countries
Canada, Czechia, Italy, North Macedonia, Romania, Serbia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All randomized patients | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 46 years |
| Region of Enrollment Canada | 2 participants |
| Region of Enrollment Czech Republic | 2 participants |
| Region of Enrollment Israel | 4 participants |
| Region of Enrollment Italy | 1 participants |
| Region of Enrollment Macedonia, The Former Yugoslav Republic of | 8 participants |
| Region of Enrollment Romania | 6 participants |
| Region of Enrollment Serbia | 2 participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 29 | 7 / 29 | 2 / 28 |
| serious Total, serious adverse events | 1 / 29 | 0 / 29 | 0 / 28 |
Outcome results
Primary
Number of HAE Attacks
Average number of HAE attacks normalized to a 28 day period
Time frame: 28 days
Population: Intent-to-Treat (ITT) Population: All patients who were randomized into one of the treatment sequences. The statistical analyses are based on the treatments to which the patient was randomized to receive during that treatment period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| rhC1INH Twice Weekly | Number of HAE Attacks | 2.74 attacks |
| rhC1INH Once Weekly | Number of HAE Attacks | 4.36 attacks |
| Placebo (Saline) Twice Weekly | Number of HAE Attacks | 7.18 attacks |
Secondary
Number of Participants With Adverse Events
Number of participants that experienced Treatment Emergent Adverse Events observed in safety population
Time frame: 20 weeks
Population: Safety Population: All patients who received at least a partial injection of study drug. The statistical analyses are based on the actual treatment the patient received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhC1INH Twice Weekly | Number of Participants With Adverse Events | 10 Participants |
| rhC1INH Once Weekly | Number of Participants With Adverse Events | 13 Participants |
| Placebo (Saline) Twice Weekly | Number of Participants With Adverse Events | 8 Participants |
Secondary
Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks
Percentage of participants achieving at least 50% reduction in the number of attacks normalized to a 28-day period as compared to the placebo treatment period
Time frame: 28 days
Population: Both the rhC1INH twice weekly treatments and the rhC1INH once weekly treatment periods are compared to the placebo treatment for the safety population. One subject withdrew before receiving any treatment and is excluded from the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| rhC1INH Twice Weekly | Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks | 74 percentage of participants |
| rhC1INH Once Weekly | Percentage of Participants Achieving at Least 50% Reduction in Number of Attacks | 42 percentage of participants |
Other Pre-specified
Immunogenicity
Number of participants analyzed for neutralizing C1INH-specific antibodies and neutralizing rhC1INH-specific antibodies after confirmed anti-C1INH and anti rhC1INH IgM or IgG antibodies
Time frame: 20 weeks
Population: Participants analyzed for Neutralizing antibodies after confirmed testing of anti-C1INH and anti rhC1INH IgM or IgG antibodies. Count of participants displays the number of positives.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rhC1INH Twice Weekly | Immunogenicity | 0 Participants |
| rhC1INH Once Weekly | Immunogenicity | 0 Participants |
| Placebo (Saline) Twice Weekly | Immunogenicity | 0 Participants |