Trial Outcomes & Findings for EASSI - Evaluation of the Safety of Self-Administration With Icatibant (NCT NCT00997204)

NCT ID: NCT00997204

Last Updated: 2021-06-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

151 participants

Primary outcome timeframe

7 days from the beginning of each phase

Results posted on

2021-06-11

Participant Flow

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.

Participant milestones

Participant milestones
Measure
Naive Subjects/ Naive Treatment Phase
Patients who had never received icatibant before this phase, got treatment of Acute HAE Attack with SC icatibant (30 mg)Administered at Site by Health Care Provider.
Non-Naive Subjects/ Self-administration Phase
Subjects who had received treatment for HAE with icatibant in previous clinical trials or had been previously treated with the marketed product Firazyr®, got Treatment of Acute HAE Attack with SC icatibant (30 mg)Self-Administered.
Naive Treatment Phase
STARTED
25
79
Naive Treatment Phase
COMPLETED
19
0
Naive Treatment Phase
NOT COMPLETED
6
79
Self-administration Phase
STARTED
19
78
Self-administration Phase
COMPLETED
19
77
Self-administration Phase
NOT COMPLETED
0
1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

EASSI - Evaluation of the Safety of Self-Administration With Icatibant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Non-Naive Patients
n=79 Participants
Patients who previously treated with icatibant in clinical studies or with commercial Firazyr® and got the treatment during the self-administered phase
Naive Patients
n=25 Participants
Patients who had never received icatibant and treated in both the Naive treatment phase and the Self-administered phase
Total
n=104 Participants
Total of all reporting groups
Age, Continuous
40.607 years
STANDARD_DEVIATION 13.044 • n=99 Participants
44.68 years
STANDARD_DEVIATION 16.53 • n=107 Participants
41.58 years
STANDARD_DEVIATION 13.98 • n=206 Participants
Sex: Female, Male
Female
52 Participants
n=99 Participants
16 Participants
n=107 Participants
68 Participants
n=206 Participants
Sex: Female, Male
Male
27 Participants
n=99 Participants
9 Participants
n=107 Participants
36 Participants
n=206 Participants
Region of Enrollment
France
6 Participants
n=99 Participants
0 Participants
n=107 Participants
6 Participants
n=206 Participants
Region of Enrollment
Argentina
18 Participants
n=99 Participants
5 Participants
n=107 Participants
23 Participants
n=206 Participants
Region of Enrollment
Spain
9 Participants
n=99 Participants
2 Participants
n=107 Participants
11 Participants
n=206 Participants
Region of Enrollment
Denmark
5 Participants
n=99 Participants
0 Participants
n=107 Participants
5 Participants
n=206 Participants
Region of Enrollment
Austria
9 Participants
n=99 Participants
5 Participants
n=107 Participants
14 Participants
n=206 Participants
Region of Enrollment
Israel
15 Participants
n=99 Participants
0 Participants
n=107 Participants
15 Participants
n=206 Participants
Region of Enrollment
Germany
9 Participants
n=99 Participants
5 Participants
n=107 Participants
14 Participants
n=206 Participants
Region of Enrollment
Italy
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Region of Enrollment
Switzerland
1 Participants
n=99 Participants
1 Participants
n=107 Participants
2 Participants
n=206 Participants
Region of Enrollment
United Kingdom
6 Participants
n=99 Participants
6 Participants
n=107 Participants
12 Participants
n=206 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Naive Subjects Administered Icatibant by Health Care Provider
n=22 Participants
The first HAE attack of naïve subjects enrolled in the study was treated at the study site, where a Health Care Provider administered icatibant to the subject. 3 subjects (of the original 25 enrolled in the naive treatment phase)self-administered icatibant while observed bu HCP, as opposed to having the HCP perform the injection. these data were not included in the naive treatment safety analyses.
Subjects Who Self-administered Icatibant (Naive)
n=19 Participants
Naive subjects self-administered the study drug at home or other site convenient to the subject, but not at the investigational site, nor under HCP-supervision.
Subjects Who Self-administered Icatibant (Non-naive)
n=78 Participants
Non-Naive subjects self-administered the study drug at home or other site convenient to the subject, but not at the investigational site, nor under HCP-supervision.
Number of Participants With Adverse Events in Self-treatment of Acute HAE Attacks With s.c. Injections of Icatibant
11 participants
6 participants
27 participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Naive Subjects Administered Icatibant by Health Care Provider
n=22 Participants
The first HAE attack of naïve subjects enrolled in the study was treated at the study site, where a Health Care Provider administered icatibant to the subject. 3 subjects (of the original 25 enrolled in the naive treatment phase)self-administered icatibant while observed bu HCP, as opposed to having the HCP perform the injection. these data were not included in the naive treatment safety analyses.
Subjects Who Self-administered Icatibant (Naive)
n=19 Participants
Naive subjects self-administered the study drug at home or other site convenient to the subject, but not at the investigational site, nor under HCP-supervision.
Subjects Who Self-administered Icatibant (Non-naive)
n=78 Participants
Non-Naive subjects self-administered the study drug at home or other site convenient to the subject, but not at the investigational site, nor under HCP-supervision.
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
Interval 1.0 to 4.2
3.1 Hours
Interval 2.0 to 4.0
2.0 Hours
Interval 1.0 to 5.3

Adverse Events

Naive Subjects Administered Icatibant by Health Care Provider

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Subjects Who Self-administered Icatibant (Naive)

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Subjects Who Self-administered Icatibant (Non-naive)

Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Naive Subjects Administered Icatibant by Health Care Provider
n=22 participants at risk
The first HAE attack of naïve subjects enrolled in the study was treated at the study site, where a Health Care Provider administered icatibant to the subject.
Subjects Who Self-administered Icatibant (Naive)
n=19 participants at risk
Naive subjects self-administered the study drug at home or other site convenient to the subject, but not at the investigational site, nor under HCP-supervision.
Subjects Who Self-administered Icatibant (Non-naive)
n=78 participants at risk
Non-naive subjects self-administered the study drug at home or other site convenient to the subject, but not at the investigational site, nor under HCP-supervision.
Congenital, familial and genetic disorders
Hereditary Angioedema
27.3%
6/22 • 7 days from the beginning of each phase
15.8%
3/19 • 7 days from the beginning of each phase
24.4%
19/78 • 7 days from the beginning of each phase
Nervous system disorders
Headache
4.5%
1/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
2.6%
2/78 • 7 days from the beginning of each phase
Investigations
Blood pressure increased
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
General disorders
Feeling Hot
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
General disorders
Local Swelling
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
General disorders
Edema Peripheral
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
General disorders
Localized edema
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
Skin and subcutaneous tissue disorders
Skin Lesion
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase
Respiratory, thoracic and mediastinal disorders
Laryngeal edema
0.00%
0/22 • 7 days from the beginning of each phase
5.3%
1/19 • 7 days from the beginning of each phase
0.00%
0/78 • 7 days from the beginning of each phase

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60