Trial Outcomes & Findings for Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema (NCT NCT00097695)

Last Updated: 2021-06-09

Results Overview

The primary efficacy endpoint was TOSR assessed by the patient using a Visual Analogue Scale (VAS). The VAS is a scale used to measure intensity of each symptom of the attack at baseline and at the pre-determined time points throughout treatment period. It consists of a horizontal 10cm line, with the 0 point corresponding to a state where patient experiences no symptoms at all and the 10cm point represents the worst symptoms ever experienced by patient. The patient indicates his/her current state of symptoms by drawing a mark across the horizontal line. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the 3 primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain. The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

84 participants

Primary outcome timeframe

5 days

Results posted on

2021-06-09

Participant Flow

Patients must have an eligible HAE attack to be randomized.64 patients were in the controlled phase(27icatibant,29 placebo,8subjects with laryngeal attacks were treated with open label icatibant).A total of 72 were treated in the open label phase(20 entered directly into the OLE phase+ 52 from the controlled phase).

Participant milestones

Participant milestones
Measure	Randomized -Icatibant Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.	Randomized -Placebo Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack.	Controlled Open-label / Laryngeal Attack Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase.	Untreated Patients at the Baseline Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing.
The Controlled Phase STARTED	27	29	8	20
The Controlled Phase COMPLETED	23	26	3	0
The Controlled Phase NOT COMPLETED	4	3	5	20
The Open Label Extension (OLE) Phase STARTED	23	26	3	20
The Open Label Extension (OLE) Phase COMPLETED	10	11	1	15
The Open Label Extension (OLE) Phase NOT COMPLETED	13	15	2	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Subcutaneous Treatment With Icatibant for Acute Attacks of Hereditary Angioedema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized -Icatibant n=27 Participants Patients who were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.	Randomized -Placebo n=29 Participants Patients who were randomized to placebo in the controlled phase after they had an eligible first in-study attack.	Controlled Open-label / Laryngeal Attack n=8 Participants patients who received first treatment Open-Label due to laryngeal symptoms	Untreated Patients at the Baseline n=20 Participants Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing.	Total n=84 Participants Total of all reporting groups
Age, Continuous	34.8 Years STANDARD_DEVIATION 9.81 • n=5 Participants	34.9 Years STANDARD_DEVIATION 11.37 • n=7 Participants	47.1 Years STANDARD_DEVIATION 13.86 • n=5 Participants	37.4 Years STANDARD_DEVIATION 11.48 • n=4 Participants	36.6 Years STANDARD_DEVIATION 11.5 • n=21 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	21 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants	57 Participants n=21 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	27 Participants n=21 Participants

PRIMARY outcome

Timeframe: 5 days

Population: Time to onset of symptom relief - Controlled phase - ITT population (patients experiencing moderate to very severe acute cutaneous and/or abdominal HAE attacks)

Outcome measures

Outcome measures
Measure	Randomized -Icatibant n=27 Participants 27 Patients were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.	Randomized -Placebo n=29 Participants 29 Patients were randomized to placebo in the controlled phase after they had an eligible first in-study attack.
Time to Onset of Symptom Relief (TOSR)	2.5 Hours Interval 1.1 to 6.0	4.6 Hours Interval 1.8 to 10.2

SECONDARY outcome

Timeframe: 5 days

This parameter assessed the time to regression (start of improvement) of observable(visible) symptoms according to the patients. Patients were asked "Report date and time when you feel that your symptoms start to improve".

Outcome measures

Outcome measures
Measure	Randomized -Icatibant n=27 Participants 27 Patients were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.	Randomized -Placebo n=29 Participants 29 Patients were randomized to placebo in the controlled phase after they had an eligible first in-study attack.
Time to Regression (Start of Improvement) According to Patient	0.8 Hours Interval 0.5 to 2.0	16.9 Hours Interval 3.2 to 14 patients were censored in the placebo group; these patients were censored as no data for time to regression (start of improvement) according to the patient were documented within the observation period.

SECONDARY outcome

Timeframe: 5 days

The time to almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least 3 consecutive measurements for all symptom.

Outcome measures

Outcome measures
Measure	Randomized -Icatibant n=27 Participants 27 Patients were randomized to icatibant in the controlled phase after they had an eligible first in-study attack.	Randomized -Placebo n=29 Participants 29 Patients were randomized to placebo in the controlled phase after they had an eligible first in-study attack.
Time to Almost Complete Symptom Relief	8.5 Hours Interval 2.5 to 31.5	19.4 Hours Interval 10.2 to 55.7

Adverse Events

Controlled Phase- Icatibant (Randomized Subjects )

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Controlled Phase- Placebo (Randomized Subjects

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack)

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Open Label Extension Phase- Icatibant (Previously Randomized)

Serious events: 3 serious events

Other events: 39 other events

Deaths: 0 deaths

Open Label Extension -Icatibant (Subjects w/ Laryngeal Attack)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Open Label Extension Phase(Untreated Patients at the Baseline)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Controlled Phase- Icatibant (Randomized Subjects ) n=27 participants at risk Patients who were randomized to icatibant in the controlled and experienced adverse events while participating in the controlled phase.	Controlled Phase- Placebo (Randomized Subjects n=29 participants at risk Patients who were randomized to placebo in the controlled phase and experienced adverse events while participating in the controlled phase.	Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) n=8 participants at risk This represents adverse events during the controlled phase that were experienced by Patients with laryngeal symptoms at the baseline and were treated with open label icatibant during the controlled phase.	Open Label Extension Phase- Icatibant (Previously Randomized) n=49 participants at risk Patients who were randomized to either icatibant or placebo in the controlled phase and experienced adverse events while participating in the open label extension phase.	Open Label Extension -Icatibant (Subjects w/ Laryngeal Attack) n=3 participants at risk This represents adverse events during the open label extension phase that were experienced by Patients with laryngeal symptoms at the baseline and got treated with open label icatibant during the controlled phase.	Open Label Extension Phase(Untreated Patients at the Baseline) n=20 participants at risk This represents adverse events experienced by Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing.
Congenital, familial and genetic disorders HAE attack	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • Number of events 1 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	2.0% 1/49 • Number of events 1 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Gastrointestinal disorders Pancreatitis	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	2.0% 1/49 • Number of events 1 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
General disorders Chest Pain	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	2.0% 1/49 • Number of events 1 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.

Other adverse events

Other adverse events
Measure	Controlled Phase- Icatibant (Randomized Subjects ) n=27 participants at risk Patients who were randomized to icatibant in the controlled and experienced adverse events while participating in the controlled phase.	Controlled Phase- Placebo (Randomized Subjects n=29 participants at risk Patients who were randomized to placebo in the controlled phase and experienced adverse events while participating in the controlled phase.	Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) n=8 participants at risk This represents adverse events during the controlled phase that were experienced by Patients with laryngeal symptoms at the baseline and were treated with open label icatibant during the controlled phase.	Open Label Extension Phase- Icatibant (Previously Randomized) n=49 participants at risk Patients who were randomized to either icatibant or placebo in the controlled phase and experienced adverse events while participating in the open label extension phase.	Open Label Extension -Icatibant (Subjects w/ Laryngeal Attack) n=3 participants at risk This represents adverse events during the open label extension phase that were experienced by Patients with laryngeal symptoms at the baseline and got treated with open label icatibant during the controlled phase.	Open Label Extension Phase(Untreated Patients at the Baseline) n=20 participants at risk This represents adverse events experienced by Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing.
Investigations Dizziness	7.4% 2/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	3.4% 1/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	33.3% 1/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Nervous system disorders Headache/Migraine	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	6.9% 2/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	25.0% 2/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	66.7% 2/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	5.0% 1/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Congenital, familial and genetic disorders Hereditary angioedema	14.8% 4/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	17.2% 5/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	50.0% 4/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	34.7% 17/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	33.3% 1/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	25.0% 5/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Gastrointestinal disorders Nausea	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	10.3% 3/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	4.1% 2/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	6.9% 2/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	7.4% 2/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Infections and infestations Infections	14.8% 4/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	13.8% 4/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	12.5% 1/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	40.8% 20/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	35.0% 7/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
General disorders Administration site conditions	11.1% 3/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	13.8% 4/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	22.4% 11/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	33.3% 1/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	15.0% 3/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Injury, poisoning and procedural complications Contusion	0.00% 0/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	6.1% 3/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.
Investigations Blood Creatine Phosphokinase Increased	3.7% 1/27 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/29 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	0.00% 0/8 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	2.0% 1/49 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	33.3% 1/3 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.	10.0% 2/20 • An AE was assigned to the controlled phase if the event start date was between the first treatment of the first attack and the first treatment in the OLE phase.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60