Trial Outcomes & Findings for Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced Angioedema (NCT NCT01343823)

NCT ID: NCT01343823

Last Updated: 2021-06-11

Results Overview

Compare the proportion of patients meeting prespecified discharge criteria in the group receiving ecallantide with conventional therapy to patients receiving placebo with conventional therapy. Patients were evaluated against 6 discharge eligibility criteria at 1,2,3,4,5, and 6 hours after study drug administration or until discharged from the ER. A responder was defined as a patient meeting all six discharge eligibility criteria as below: • Improvement of edema to "a little better" or "a lot better" as assessed by health care provider using a five point scale • Stable vital signs (within an acceptable range) • Absence of stridor • Absence of dyspnea or use of accessory muscles during respiration • Absence of drooling • Able to drink without difficulty

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

79 participants

Primary outcome timeframe

6 hours

Results posted on

2021-06-11

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Administered by two subcutaneous injections.
Ecallantide 10 mg
10 mg administered as one 10 mg SC injection of ecallantide and one matching placebo
Ecallantide 30 mg
30 mg administered as one 30 mg SC injection of ecallantide and one matching placebo
Ecallantide 60mg
60 mg administered as two 30 mg SC injections of ecallantide
Overall Study
STARTED
20
20
19
20
Overall Study
COMPLETED
18
20
19
19
Overall Study
NOT COMPLETED
2
0
0
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Administered by two subcutaneous injections.
Ecallantide 10 mg
10 mg administered as one 10 mg SC injection of ecallantide and one matching placebo
Ecallantide 30 mg
30 mg administered as one 30 mg SC injection of ecallantide and one matching placebo
Ecallantide 60mg
60 mg administered as two 30 mg SC injections of ecallantide
Overall Study
Study Terminated
1
0
0
1
Overall Study
Withdrawal by Subject
1
0
0
0

Baseline Characteristics

Evaluation of Ecallantide for Treatment of Angiotensin Converting Enzyme (ACE) Inhibitor Induced Angioedema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ecallantide 10 mg
n=20 Participants
Ecallantide 30 mg
n=19 Participants
Ecallantide 60 mg
n=19 Participants
Placebo
n=18 Participants
Total
n=76 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Categorical
Between 18 and 65 years
15 Participants
n=5 Participants
14 Participants
n=7 Participants
13 Participants
n=5 Participants
12 Participants
n=4 Participants
54 Participants
n=21 Participants
Age, Categorical
>=65 years
5 Participants
n=5 Participants
5 Participants
n=7 Participants
6 Participants
n=5 Participants
6 Participants
n=4 Participants
22 Participants
n=21 Participants
Sex: Female, Male
Female
13 Participants
n=5 Participants
8 Participants
n=7 Participants
9 Participants
n=5 Participants
11 Participants
n=4 Participants
41 Participants
n=21 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
11 Participants
n=7 Participants
10 Participants
n=5 Participants
7 Participants
n=4 Participants
35 Participants
n=21 Participants
Region of Enrollment
United States
20 Participants
n=5 Participants
19 Participants
n=7 Participants
19 Participants
n=5 Participants
18 Participants
n=4 Participants
76 Participants
n=21 Participants

PRIMARY outcome

Timeframe: 6 hours

Population: Safety Population

Compare the proportion of patients meeting prespecified discharge criteria in the group receiving ecallantide with conventional therapy to patients receiving placebo with conventional therapy. Patients were evaluated against 6 discharge eligibility criteria at 1,2,3,4,5, and 6 hours after study drug administration or until discharged from the ER. A responder was defined as a patient meeting all six discharge eligibility criteria as below: • Improvement of edema to "a little better" or "a lot better" as assessed by health care provider using a five point scale • Stable vital signs (within an acceptable range) • Absence of stridor • Absence of dyspnea or use of accessory muscles during respiration • Absence of drooling • Able to drink without difficulty

Outcome measures

Outcome measures
Measure
Placebo
n=18 Participants
Ecallantide 10 mg
n=20 Participants
Ecallantide 30 mg
n=19 Participants
Ecallantide 60 mg
n=19 Participants
Safety and Efficacy of Ecallantide
13 participants
Not calculated
17 participants
Interval -18.8 to 43.1
17 participants
Interval -15.9 to 45.9
17 participants
Interval -15.9 to 45.9

SECONDARY outcome

Timeframe: 6 hours

Population: Time to Symptom Resolution Based on the VAS (Safety Population)

Compare the time to onset of symptom resolution between the ecallantide-treated and placebo-treated groups. The patient assessed severity of the angioedema attack using a VAS at baseline and following study drug administration every 15 minutes for the first 2 hours and then every 30 minutes through 6 hours post dosing or until the time of discharge from the ER (whichever occurred first). The scale ranged from "totally resolved" to "very severe".

Outcome measures

Outcome measures
Measure
Placebo
n=18 Participants
Ecallantide 10 mg
n=20 Participants
Ecallantide 30 mg
n=19 Participants
Ecallantide 60 mg
n=19 Participants
Time to Symptom Resolution Based on the Visual Analog Scale (VAS)
0.50 hours
Interval 0.25 to 1.5
0.30 hours
Interval 0.25 to 0.73
0.27 hours
Interval 0.23 to 1.0
0.50 hours
Interval 0.22 to 2.02

Adverse Events

Ecallantide 10 mg

Serious events: 6 serious events
Other events: 7 other events
Deaths: 0 deaths

Ecallantide 30 mg

Serious events: 8 serious events
Other events: 11 other events
Deaths: 0 deaths

Ecallantide 60 mg

Serious events: 8 serious events
Other events: 12 other events
Deaths: 0 deaths

Placebo

Serious events: 5 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ecallantide 10 mg
n=20 participants at risk
Ecallantide 30 mg
n=19 participants at risk
Ecallantide 60 mg
n=19 participants at risk
Placebo
n=18 participants at risk
Skin and subcutaneous tissue disorders
Angioedema
25.0%
5/20 • Number of events 19
31.6%
6/19
36.8%
7/19
22.2%
4/18
Cardiac disorders
Tachycardia
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Vascular disorders
Hypertension
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Investigations
ECG T Wave Abnormal
5.0%
1/20 • Number of events 1
0.00%
0/19
0.00%
0/19
0.00%
0/18
Nervous system disorders
Dizziness
5.0%
1/20 • Number of events 1
0.00%
0/19
0.00%
0/19
0.00%
0/18
Renal and urinary disorders
Renal Failure Acute
5.0%
1/20 • Number of events 1
0.00%
0/19
0.00%
0/19
0.00%
0/18
Gastrointestinal disorders
Dysphagia
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Skin and subcutaneous tissue disorders
Angioedema (Epiglottic)
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Skin and subcutaneous tissue disorders
Angioedema (Laryngeal)
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Nervous system disorders
Carotid Artery Stenosis
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Respiratory, thoracic and mediastinal disorders
Respiratory Arrest
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18

Other adverse events

Other adverse events
Measure
Ecallantide 10 mg
n=20 participants at risk
Ecallantide 30 mg
n=19 participants at risk
Ecallantide 60 mg
n=19 participants at risk
Placebo
n=18 participants at risk
Blood and lymphatic system disorders
Anemia
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Cardiac disorders
Tachycardia
0.00%
0/20
0.00%
0/19
0.00%
0/19
11.1%
2/18
Gastrointestinal disorders
Abdominal Pain
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Gastrointestinal disorders
Abdominal Pain Lower
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Gastrointestinal disorders
Diarrhoea
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Gastrointestinal disorders
Dysphagia
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Gastrointestinal disorders
GERD
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
General disorders
Asthenia
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
General disorders
Injection Site Pain
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
General disorders
Injection Site Swelling
5.0%
1/20
0.00%
0/19
0.00%
0/19
0.00%
0/18
Infections and infestations
Gastrointestinal Viral Infection
5.0%
1/20
0.00%
0/19
0.00%
0/19
0.00%
0/18
Infections and infestations
Oral Candidiasis
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Investigations
aPTT Prolonged
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Investigations
Blood Alkaline Phosphatase Increase
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Investigations
Blood Creatinine Increase
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Investigations
Blood Glucose
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Investigations
Blood Potassium Abnormal
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Investigations
ECG T Wave Abnormal
5.0%
1/20
0.00%
0/19
0.00%
0/19
0.00%
0/18
Investigations
GGT Increase
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Investigations
Platelet Count Decrease
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Metabolism and nutrition disorders
Hyperglycaemia
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Musculoskeletal and connective tissue disorders
Muscle Spasms
5.0%
1/20
0.00%
0/19
0.00%
0/19
0.00%
0/18
Musculoskeletal and connective tissue disorders
Pain in Extremity
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Nervous system disorders
Carotid Artery Stenosis
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Nervous system disorders
Dizziness
5.0%
1/20
0.00%
0/19
0.00%
0/19
0.00%
0/18
Nervous system disorders
Headache
5.0%
1/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Nervous system disorders
Hypoaesthesia
5.0%
1/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Renal and urinary disorders
Haematuria
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Renal and urinary disorders
Renal Failure Acute
5.0%
1/20
0.00%
0/19
0.00%
0/19
0.00%
0/18
Respiratory, thoracic and mediastinal disorders
Allergic Respiratory Symptom
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Respiratory, thoracic and mediastinal disorders
Oopharyngeal Pain
0.00%
0/20
0.00%
0/19
5.3%
1/19
0.00%
0/18
Respiratory, thoracic and mediastinal disorders
Respiratory Arrest
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Skin and subcutaneous tissue disorders
Angioedema
25.0%
5/20
42.1%
8/19
36.8%
7/19
22.2%
4/18
Skin and subcutaneous tissue disorders
Hyperhidrosis
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Skin and subcutaneous tissue disorders
Rash Pruritic
0.00%
0/20
5.3%
1/19
0.00%
0/19
0.00%
0/18
Vascular disorders
Flushing
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18
Vascular disorders
Hypertension
0.00%
0/20
0.00%
0/19
0.00%
0/19
5.6%
1/18

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Results disclosure agreements

  • Principal investigator is a sponsor employee Dyax agreements vary, but Dyax will not prohibit any investigator from publishing. Dyax reviews publications prior to public release and can request deferral by up to 60 days beyond the proposed publication date if necessary to preserve its intellectual property. Dyax can request changes to publications to remove non-study-related confidential information. Dyax can also request deferral of single-center publications until after disclosure of the clinical trial's primary publication.
  • Publication restrictions are in place

Restriction type: OTHER