Trial Outcomes & Findings for Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE) (NCT NCT00457015)
NCT ID: NCT00457015
Last Updated: 2021-06-08
Results Overview
The Mean Symptom Complex Severity (MSCS) score is a validated, comprehensive point-in-time measure of symptom severity. At baseline and 4 hours, patients rated the severity on a categorical scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more.
COMPLETED
PHASE3
96 participants
baseline, 4 hours post-dose
2021-06-08
Participant Flow
Patients were screened in advance of presenting with an HAE attack but were randomized only upon attack.
Participant milestones
| Measure |
KALBITOR (Ecallantide)
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Overall Study
STARTED
|
48
|
48
|
|
Overall Study
COMPLETED
|
48
|
47
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
KALBITOR (Ecallantide)
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Overall Study
Left study site against medical advice
|
0
|
1
|
Baseline Characteristics
Efficacy Study of DX-88 (Ecallantide) to Treat Acute Attacks of Hereditary Angioedema (HAE)
Baseline characteristics by cohort
| Measure |
KALBITOR (Ecallantide)
n=48 Participants
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=48 Participants
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
Total
n=96 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.0 years
STANDARD_DEVIATION 13.12 • n=99 Participants
|
38.0 years
STANDARD_DEVIATION 12.19 • n=107 Participants
|
37.5 years
STANDARD_DEVIATION 12.61 • n=206 Participants
|
|
Sex: Female, Male
Female
|
37 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
65 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
31 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
47 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
95 Participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Symptom Complexes at Baseline
Internal Head/Neck
|
8 symptom complexes
n=99 Participants
|
13 symptom complexes
n=107 Participants
|
21 symptom complexes
n=206 Participants
|
|
Symptom Complexes at Baseline
Stomach/GI
|
18 symptom complexes
n=99 Participants
|
27 symptom complexes
n=107 Participants
|
45 symptom complexes
n=206 Participants
|
|
Symptom Complexes at Baseline
Genital/Buttocks
|
6 symptom complexes
n=99 Participants
|
5 symptom complexes
n=107 Participants
|
11 symptom complexes
n=206 Participants
|
|
Symptom Complexes at Baseline
External Head/Neck
|
14 symptom complexes
n=99 Participants
|
9 symptom complexes
n=107 Participants
|
23 symptom complexes
n=206 Participants
|
|
Symptom Complexes at Baseline
Cutaneous
|
34 symptom complexes
n=99 Participants
|
21 symptom complexes
n=107 Participants
|
55 symptom complexes
n=206 Participants
|
PRIMARY outcome
Timeframe: baseline, 4 hours post-dosePopulation: Patients were excluded from the analysis if they did not have data for the endpoint being analyzed. Reasons for patients being excluded are for ecallantide: 1 patient treated for severe upper airway compromise; for placebo: 3 patient treated for severe upper airway compromise and 3 patients with missing 4-hour data. Best score=0.0; worst score=3.0.
The Mean Symptom Complex Severity (MSCS) score is a validated, comprehensive point-in-time measure of symptom severity. At baseline and 4 hours, patients rated the severity on a categorical scale (0 = normal, 1 = mild, 2 = moderate, 3 = severe) for symptoms at each affected anatomical location. Ratings were averaged to obtain the MSCS score. A decrease in MSCS score reflected an improvement in symptoms; clinically meaningful improvement was indicated by a reduction in the score of 0.30 or more.
Outcome measures
| Measure |
KALBITOR (Ecallantide)
n=47 Participants
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=42 Participants
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
MSCS Score at baseline
|
2.2 units on a scale
Standard Deviation 0.50
|
2.0 units on a scale
Standard Deviation 0.35
|
|
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
MSCS Score at 4 hours post-dose
|
1.4 units on a scale
Standard Deviation 0.75
|
1.6 units on a scale
Standard Deviation 0.77
|
|
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
Change from baseline in MSCS at 4 hours post-dose
|
-0.8 units on a scale
Standard Deviation 0.63
|
-0.4 units on a scale
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: 4 hours post-dosePopulation: Patients were excluded from this analysis if they did not have data for the endpoint being analyzed. The reasons for patients being excluded from this analysis are for ecallantide: 1 patient treated for severe upper airway compromise and for placebo: 3 patient treated for severe upper airway compromise and 3 patients with missing 4-hour data.
Treatment Outcome Score (TOS) is a validated, comprehensive measure of symptom response to treatment. At 4 hours , patient assessment of response characterized by their change from baseline in symptom severity and collected by anatomic site of attack involvement, was recorded on a categorical scale (significant improvement \[100; best value\]to significant worsening \[-100; worst value\]). Clinically meaningful improvement was indicated by a TOS of 30 or higher.
Outcome measures
| Measure |
KALBITOR (Ecallantide)
n=47 Participants
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=42 Participants
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Treatment Outcome Score at 4 Hours Post-Dose
|
53.4 units on a scale
Standard Deviation 49.70
|
8.1 units on a scale
Standard Deviation 63.18
|
SECONDARY outcome
Timeframe: 4 hours post-dosePopulation: The time to significant improvement is not provided in this display as the estimated median times were not reached by 240 minutes. Instead, the number of patients with significant improvement is provided per treatment arm.
Patients were to be asked to perform an overall response assessment at intervals during the first 4 hours post-dose. Assessments were to be made relative to baseline (ie, immediately before initial dosing) using a 5-category scale. Categories were: significant improvement = "a lot better or resolved"; improvement = "a little better"; same = response unchanged; worsening = "a little worse"; significant worsening = "a lot worse". Significant improvement is the first time that a patient responded to the overall response assessment as "a lot better or resolved."
Outcome measures
| Measure |
KALBITOR (Ecallantide)
n=48 Participants
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=48 Participants
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Patients With Significant Improvement in Overall Response
|
22 participants
|
12 participants
|
SECONDARY outcome
Timeframe: baseline, 4 hours post-dosingPopulation: Diary information was not available for 1 patient in the placebo arm. This patient was considered not evaluable and excluded from the analysis.
A successful response was defined as improvement in existing laryngeal symptom complex,stabilization of an existing peripheral symptom complex, or a change from baseline in the MSCS score at 4 hours of at least -1.0.
Outcome measures
| Measure |
KALBITOR (Ecallantide)
n=48 Participants
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=47 Participants
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score
|
45 participants
|
28 participants
|
SECONDARY outcome
Timeframe: 24 hours post-dosingPopulation: Diary information was not available for 1 patient in the placebo arm. This patient was considered not evaluable and excluded from the analysis.
Maintenance of significant improvement was defined as achieving and maintaining a significant improvement in overall response through 24 hours after dosing. Patient response categories were: significant improvement = "a lot better or resolved"; improvement = "a little better"; same = response unchanged; worsening = "a little worse"; significant worsening = "a lot worse".
Outcome measures
| Measure |
KALBITOR (Ecallantide)
n=48 Participants
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=47 Participants
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours
|
21 participants
|
10 participants
|
Adverse Events
KALBITOR (Ecallantide)
Placebo
Serious adverse events
| Measure |
KALBITOR (Ecallantide)
n=48 participants at risk
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=48 participants at risk
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Congenital, familial and genetic disorders
Hereditary angioedema
|
0.00%
0/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
6.2%
3/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
Other adverse events
| Measure |
KALBITOR (Ecallantide)
n=48 participants at risk
KALBITOR (ecallantide, DX-88) 30 mg given as three 10 mg/mL subcutaneous injections.
|
Placebo
n=48 participants at risk
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
6.2%
3/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
|
Nervous system disorders
Headache
|
4.2%
2/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
10.4%
5/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
|
Gastrointestinal disorders
Nausea
|
6.2%
3/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
2.1%
1/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
6.2%
3/48 • up to 7 days post-dose
For patients that were given an open-label dose of ecallantide for severe upper airway compromise or failed or incomplete response, or relapse, all adverse events occurring prior to open-label dosing are included in the following tables where all patients are presented in the double-blind, randomized treatment groups.
|
Additional Information
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