Hereditary Angioedema (HAE)
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of repeated doses of ecallantide in the treatment of acute attacks of hereditary angioedema and to allow HAE patients continued access to ecallantide. In addition, patients enrolled in DX-88/20 (EDEMA4) trial will be followed up and treated for subsequent attacks in this trial.
Detailed description
This is an open label trial. The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide in the treatment of acute attacks of hereditary angioedema. This study is designed to provide efficacy and safety data on repeated use of ecallantide. These data are intended to support the marketing authorization of ecallantide in the treatment of acute attacks of hereditary angioedema. Efficacy and safety of ecallantide will be evaluated in this study.
Interventions
DRUGecallantide
solution for SC injection, one 30 mg dose per HAE attack
Sponsors
Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 10 years of age or older * Documented diagnosis of HAE (Type I or II) * Willing and able to give informed consent * Acute HAE attack at time of presentation
Exclusion criteria
* Receipt of an investigational drug or device, within 30 days prior to study treatment, other than DX-88 (ecallantide) * Pregnancy or breastfeeding * Receipt of non-investigational C1-INH or DX-88 within 72 hours of treatment * Patients eligible for current, ongoing clinical trial in which DX 88 (ecallantide) is offered
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | 4 hrs post dose after every episode | Mean Symptom Complex Severity (MSCS) score is a validated point-in-time measure of symptom severity. At baseline and 4 hrs, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | 4 hrs post dose after every episode | The Treatment Outcome Score (TOS)is a validated measure of response to therapy. Response assessment for each symptom complex (internal head/neck, stomach/GI, genital/buttocks, external head/neck or cutaneous) was to be weighted based on the severity of symptom complexes at baseline. Severity assessment at baseline was rated on a categorical scale (1=mild, 2=moderate, 3=severe) for symptoms at each affected symptom complex. Response assessment of each symptom complex post-dosing relative to baseline used a scale (100=significant improvement, 50=improvement, 0=same). The weighted values were used to calculate the composite TOS. A TOS greater than 0 denotes an improvement in symptoms compared with baseline severity. |
| Time to Significant Improvement | 15 min - 4 hrs post dose after every episode | Time to significant improvement in overall response based on the period from 15 minutes after dosing through 4 hrs post dosing. Significant improvement was defined as a response of a lot better or resolved in the overall response assessment. |
Countries
Canada, Jordan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment DX-88 (ecallantide) | 147 |
| Total | 147 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Continuous | 35.8 years STANDARD_DEVIATION 14.39 |
| Region of Enrollment Canada | 1 Participants |
| Region of Enrollment Jordan | 5 Participants |
| Region of Enrollment United States | 141 Participants |
| Sex: Female, Male Female | 49 Participants |
| Sex: Female, Male Male | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 102 / 147 |
| serious Total, serious adverse events | 27 / 147 |
Outcome results
Primary
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing
Mean Symptom Complex Severity (MSCS) score is a validated point-in-time measure of symptom severity. At baseline and 4 hrs, 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.
Time frame: 4 hrs post dose after every episode
Population: All efficacy analyses were to be based on the safety population (all treated patients). Only those patients with non-missing severity and response assessment were included in the change in MSCS score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 1 (n=138) | -1.04 scores on a scale | Standard Deviation 0.773 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 2 (n=98) | -1.06 scores on a scale | Standard Deviation 0.731 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 3 (n=73) | -1.07 scores on a scale | Standard Deviation 0.801 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 4 (n=52) | -1.15 scores on a scale | Standard Deviation 0.791 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 5 (n=38) | -1.16 scores on a scale | Standard Deviation 0.746 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 6 (n=32) | -1.07 scores on a scale | Standard Deviation 0.806 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 7 (n=25) | -1.24 scores on a scale | Standard Deviation 0.797 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 8 (n=22) | -1.31 scores on a scale | Standard Deviation 0.667 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 9 (n=22) | -1.20 scores on a scale | Standard Deviation 0.764 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 10 (n=16) | -1.27 scores on a scale | Standard Deviation 1.027 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 11 (n=16) | -1.22 scores on a scale | Standard Deviation 0.643 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 12 (n=12) | -1.36 scores on a scale | Standard Deviation 0.677 |
| DX-88 (Ecallantide) | Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hrs Post Dosing | change in MSCS at 4 hrs episode 13 (n=12) | -1.10 scores on a scale | Standard Deviation 0.657 |
Secondary
Time to Significant Improvement
Time to significant improvement in overall response based on the period from 15 minutes after dosing through 4 hrs post dosing. Significant improvement was defined as a response of a lot better or resolved in the overall response assessment.
Time frame: 15 min - 4 hrs post dose after every episode
Population: All efficacy analyses were to be based on the safety population (all treated patients). Only those patients with non-missing severity and response assessment were included in the change in TOS score.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 1 (n=145) | 225.2 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 2 (n=102) | 194.5 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 3 (n=77) | 225.4 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 4 (n=56) | 198.1 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 5 (n=41) | 240.0 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 6 (n=33) | 225.2 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 7 (n=27) | NA estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 8 (n=23) | 210.5 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 9 (n=23) | 169.3 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 10 (n=17) | 170.5 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 11 (n=16) | 226.5 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 12 (n=15) | 177.2 estimated time in minutes |
| DX-88 (Ecallantide) | Time to Significant Improvement | time to improvement in min. for episode 13 (n=13) | 195.2 estimated time in minutes |
Secondary
Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms
The Treatment Outcome Score (TOS)is a validated measure of response to therapy. Response assessment for each symptom complex (internal head/neck, stomach/GI, genital/buttocks, external head/neck or cutaneous) was to be weighted based on the severity of symptom complexes at baseline. Severity assessment at baseline was rated on a categorical scale (1=mild, 2=moderate, 3=severe) for symptoms at each affected symptom complex. Response assessment of each symptom complex post-dosing relative to baseline used a scale (100=significant improvement, 50=improvement, 0=same). The weighted values were used to calculate the composite TOS. A TOS greater than 0 denotes an improvement in symptoms compared with baseline severity.
Time frame: 4 hrs post dose after every episode
Population: All efficacy analyses were to be based on the safety population (all treated patients). Only those patients with non-missing severity and response assessment were included in the change in TOS score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 1 (n=140) | 69.80 scores on a scale | Standard Deviation 35.378 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 2 (n=98) | 70.05 scores on a scale | Standard Deviation 40.639 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 3 (n=73) | 63.08 scores on a scale | Standard Deviation 42.84 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 4 (n=52) | 62.65 scores on a scale | Standard Deviation 42.802 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 5 (n=39) | 65.13 scores on a scale | Standard Deviation 34.858 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 6 (n=32) | 60.42 scores on a scale | Standard Deviation 40.866 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 7 (n=25) | 56.20 scores on a scale | Standard Deviation 34.229 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 8 (n=22) | 79.77 scores on a scale | Standard Deviation 24.663 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 9 (n=22) | 71.06 scores on a scale | Standard Deviation 37.27 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 10 (n=16) | 76.30 scores on a scale | Standard Deviation 23.556 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 11 (n=16) | 60.94 scores on a scale | Standard Deviation 45.615 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 12 (n=13) | 76.92 scores on a scale | Standard Deviation 43.853 |
| DX-88 (Ecallantide) | Treatment Outcome Score (TOS) at 4 Hrs Post Dosing, Based on the Patient Assessment of Baseline Severity of Symptoms | TOS at 4 hrs for episode 13 (n=12) | 64.93 scores on a scale | Standard Deviation 46.854 |