Hereditary Angioedema
Conditions
Keywords
HAE, Type I HAE, Type II HAE
Brief summary
This study is being conducted to explore the clinical safety, local tolerability, convenience and effectiveness of self-treatment of hereditary angioedema (HAE) attacks with subcutaneous injections of icatibant.
Detailed description
This Phase IIIb study was multi-center and open-label with a single dose level. Subjects with a documented diagnosis of HAE Type I or II were eligible to participate in this trial. Eligible subjects included those who had received treatment for HAE with icatibant in previous clinical trials, or subjects who had been previously treated with the marketed product Firazyr® and subjects who were naïve to icatibant treatment. All subjects were trained on the method of self-administration at their enrollment visit (Visit 1).For the training sessions, a syringe pre-filled with 3 mL placebo solution was used in place of icatibant. Comprehensive educational material and instructions including pictograms were developed for the subjects to illustrate the method of self-administration and use of the Patient Diary. The training material provided additional information on how to self-diagnose an HAE attack and how to decide on the necessity to treat.In addition, instructions were provided on what to do in case of a laryngeal attack.
Interventions
DRUGIcatibant
Single subcutaneous injection of icatibant, 30 mg
Sponsors
Jerini AG
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient must meet the following criteria to be enrolled in this study. 1. Males and females 18 years of age at the time of informed consent 2. Documented diagnosis of HAE Type I or II based on ALL of the following criteria: * Family and/or medical history * Characteristic attack manifestations, recurrent attacks * Historical functional C1-INH \<50% normal values 3. Women of childbearing potential must use consistently and correctly a highly effective, adequate method of birth control (failure rate less than 1% per year) - sexual abstinence or have a vasectomised partner during the duration of the study. Hormonal contraception can be continued if verified by a physician that it doesn't affect the course of HAE attacks. 4. Mental and physical condition allowing patients to complete baseline assessment, to self-administer icatibant and to follow other study procedures. 5. Ability to provide signed written informed consent after all aspects of the study have been explained and discussed with the patient.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from the study. 1. Participation in a clinical trial of another investigational medicinal product within the past month (except a previous icatibant study). 2. Diagnosis of angioedema other than Type I or Type II HAE. 3. Evidence of symptomatic coronary artery disease based on medical history, in particular, unstable angina pectoris or severe coronary heart disease. 4. Congestive heart failure (NYHA Class 3 and 4). 5. Stroke within the past 6 months. 6. Treatment with angiotensin converting enzyme (ACE) inhibitor. 7. Pregnancy and/or breast-feeding. 8. In the opinion of the investigator: mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study. 9. In the opinion of the investigator: unlikely to comply with the protocol, for example, uncooperative attitude, inability to return for follow-up visits, or unlikely to complete the study for any reason. 10. In the opinion of the investigator: inability to manage study medication or self-administration of an injection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant | 7 days from the beginning of each phase | Clinical safety of self-treatment of acute HAE attacks with s.c. injections of icatibant was assessed by calculating the number of AEs occurred during the study. Only those adverse events occurring up to the earlier of 7 days from the start of the naive phase, study discontinuation and start of the self-administration phase are assessed. The Local Tolerability Assessment tool was used. Subjects and Investigators graded erythema/reddening, swelling, burning, pruritus/itching, warm sensation, and skin pain on a 0 to 3 severity scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort | 48 hours post-dose | Subjects assessed angioedema attack symptoms using the visual analogue scale (VAS) for skin pain, skin swelling and abdominal pain. The VAS is a continuous scale comprised of a 100 mm in length line, anchored by 2 verbal descriptors, one for each symptom extreme 0 (no pain) and 100 (worst pain). The respondent is asked to place a mark on the VAS line (any where between 0 and 100 mm) at the point that represents their pain intensity. The score is determined by measuring the distance (mm) on the line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. Score interpretation is: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). Symptom relief is defined as at least a 50% reduction in a pre-dose VAS score of 30 mm or greater. The time to onset of symptom relief is defined as the first of 3 consecutive assessments at which symptom relief was observed. |
Countries
Argentina, Austria, Denmark, France, Germany, Israel, Italy, Spain, Switzerland, United Kingdom
Participant flow
Pre-assignment details
Patients were screened for entry based on their known medical histories (HAE attacks) and previous exposure to a treatment (naïve or not). 151 were enrolled and trained in the self-administration. 47 of these subjects did not have an acute attack of HAE treated with icatibant during this study and were included in the untreated population.
Participants by arm
| Arm | Count |
|---|---|
| Non-Naive Patients Patients who previously treated with icatibant in clinical studies or with commercial Firazyr® and got the treatment during the self-administered phase | 79 |
| Naive Patients Patients who had never received icatibant and treated in both the Naive treatment phase and the Self-administered phase | 25 |
| Total | 104 |
Baseline characteristics
| Characteristic | Naive Patients | Total | Non-Naive Patients |
|---|---|---|---|
| Age, Continuous | 44.68 years STANDARD_DEVIATION 16.53 | 41.58 years STANDARD_DEVIATION 13.98 | 40.607 years STANDARD_DEVIATION 13.044 |
| Region of Enrollment Argentina | 5 Participants | 23 Participants | 18 Participants |
| Region of Enrollment Austria | 5 Participants | 14 Participants | 9 Participants |
| Region of Enrollment Denmark | 0 Participants | 5 Participants | 5 Participants |
| Region of Enrollment France | 0 Participants | 6 Participants | 6 Participants |
| Region of Enrollment Germany | 5 Participants | 14 Participants | 9 Participants |
| Region of Enrollment Israel | 0 Participants | 15 Participants | 15 Participants |
| Region of Enrollment Italy | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Spain | 2 Participants | 11 Participants | 9 Participants |
| Region of Enrollment Switzerland | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United Kingdom | 6 Participants | 12 Participants | 6 Participants |
| Sex: Female, Male Female | 16 Participants | 68 Participants | 52 Participants |
| Sex: Female, Male Male | 9 Participants | 36 Participants | 27 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 | 7 / 22 | 6 / 19 | 21 / 78 |
| serious Total, serious adverse events | 0 / 22 | 0 / 19 | 0 / 78 |
Outcome results
Primary
Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant
Clinical safety of self-treatment of acute HAE attacks with s.c. injections of icatibant was assessed by calculating the number of AEs occurred during the study. Only those adverse events occurring up to the earlier of 7 days from the start of the naive phase, study discontinuation and start of the self-administration phase are assessed. The Local Tolerability Assessment tool was used. Subjects and Investigators graded erythema/reddening, swelling, burning, pruritus/itching, warm sensation, and skin pain on a 0 to 3 severity scale.
Time frame: 7 days from the beginning of each phase
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Naive Subjects Administered Icatibant by Health Care Provider | Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant | 11 participants |
| Subjects Who Self-administered Icatibant (Naive) | Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant | 6 participants |
| Subjects Who Self-administered Icatibant (Non-naive) | Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant | 27 participants |
Secondary
Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort
Subjects assessed angioedema attack symptoms using the visual analogue scale (VAS) for skin pain, skin swelling and abdominal pain. The VAS is a continuous scale comprised of a 100 mm in length line, anchored by 2 verbal descriptors, one for each symptom extreme 0 (no pain) and 100 (worst pain). The respondent is asked to place a mark on the VAS line (any where between 0 and 100 mm) at the point that represents their pain intensity. The score is determined by measuring the distance (mm) on the line between the no pain anchor and the patient's mark, providing a range of scores from 0-100. A higher score indicates greater pain intensity. Score interpretation is: no pain (0-4 mm), mild pain (5-44 mm), moderate pain (45-74 mm), and severe pain (75-100 mm). Symptom relief is defined as at least a 50% reduction in a pre-dose VAS score of 30 mm or greater. The time to onset of symptom relief is defined as the first of 3 consecutive assessments at which symptom relief was observed.
Time frame: 48 hours post-dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Naive Subjects Administered Icatibant by Health Care Provider | Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort | 2.0 Hours |
| Subjects Who Self-administered Icatibant (Naive) | Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort | 3.1 Hours |
| Subjects Who Self-administered Icatibant (Non-naive) | Clinical Efficacy of Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant, Time to Symptom Relief Using VAS Score for a Single Primary Symptom by Patient Cohort | 2.0 Hours |