Trial Outcomes & Findings for Safety and Efficacy Study of Repeated Doses of DX-88 (Ecallantide) to Treat Attacks of Hereditary Angioedema (HAE) (NCT NCT00456508)

Last Updated: 2021-06-08

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

147 participants

Primary outcome timeframe

4 hrs post dose after every episode

Results posted on

2021-06-08

Participant Flow

Participant milestones

Participant milestones
Measure	DX-88 (Ecallantide) Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose.
Overall Study STARTED	147
Overall Study COMPLETED	147
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study of Repeated Doses of DX-88 (Ecallantide) to Treat Attacks of Hereditary Angioedema (HAE)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=147 Participants DX-88 (ecallantide)
Age, Continuous	35.8 years STANDARD_DEVIATION 14.39 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants
Sex: Female, Male Male	98 Participants n=5 Participants
Region of Enrollment United States	141 Participants n=5 Participants
Region of Enrollment Canada	1 Participants n=5 Participants
Region of Enrollment Jordan	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	DX-88 (Ecallantide) n=138 Participants Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose.
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
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
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
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
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
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
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
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
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
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
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
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
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 outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	DX-88 (Ecallantide) n=140 Participants Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose.
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
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
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
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
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 42.840
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
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
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
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
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 37.270
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
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
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

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	DX-88 (Ecallantide) n=145 Participants Patients were treated with DX-88 (ecallantide) when they experienced an HAE attack. 30 mg dose of ecallantide given via 3 SC injections; a second 30 mg dose can be administered if needed. Patients were to be assessed until 4 hrs post-dose. Patients were asked to return for 3 follow-up visits: 7 days, 28 days and 90 days post-dose.
Time to Significant Improvement time to improvement in min. for episode 1 (n=145)	225.2 estimated time in minutes Interval 165.4 to 228.2
Time to Significant Improvement time to improvement in min. for episode 2 (n=102)	194.5 estimated time in minutes Interval 165.2 to 227.5
Time to Significant Improvement time to improvement in min. for episode 3 (n=77)	225.4 estimated time in minutes Interval 225.1 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 4 (n=56)	198.1 estimated time in minutes Interval 165.4 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 5 (n=41)	240.0 estimated time in minutes Interval 165.3 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 6 (n=33)	225.2 estimated time in minutes Interval 137.0 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 7 (n=27)	NA estimated time in minutes Interval 195.3 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 8 (n=23)	210.5 estimated time in minutes Interval 135.3 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 9 (n=23)	169.3 estimated time in minutes Interval 135.4 to 240.0
Time to Significant Improvement time to improvement in min. for episode 10 (n=17)	170.5 estimated time in minutes Interval 165.1 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 11 (n=16)	226.5 estimated time in minutes Interval 145.7 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 12 (n=15)	177.2 estimated time in minutes Interval 113.8 to N/A: significant improvement in overall response was not reached within 4 hours.
Time to Significant Improvement time to improvement in min. for episode 13 (n=13)	195.2 estimated time in minutes Interval 135.1 to N/A: significant improvement in overall response was not reached within 4 hours.

Adverse Events

Treatment

Serious events: 27 serious events

Other events: 102 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=147 participants at risk DX-88 (ecallantide)
Congenital, familial and genetic disorders hereditary angioedema	11.6% 17/147 • Number of events 17 • pre-dose to 28 days (+/-2 days) post dose
Immune system disorders hypersensitivity	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Immune system disorders anaphylactic reaction	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Blood and lymphatic system disorders anemia	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Gastrointestinal disorders abdominal distension	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Gastrointestinal disorders abdominal pain	2.7% 4/147 • Number of events 4 • pre-dose to 28 days (+/-2 days) post dose
Hepatobiliary disorders cholecystitis	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Infections and infestations otitis externa	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Infections and infestations cellulitis staphyloccal	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Injury, poisoning and procedural complications contusion	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Injury, poisoning and procedural complications transfusion reaction	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Investigations liver function test abnormal	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Investigations white blood cell count increased	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Metabolism and nutrition disorders dehydration	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Neoplasms benign, malignant and unspecified (incl cysts and polyps) chronic myeloid leukaemia	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Neoplasms benign, malignant and unspecified (incl cysts and polyps) lipoma	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Psychiatric disorders anxiety	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Respiratory, thoracic and mediastinal disorders laryngeal oedema	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Respiratory, thoracic and mediastinal disorders pulmonary embolism	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Skin and subcutaneous tissue disorders erythema	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Skin and subcutaneous tissue disorders pruritus	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Skin and subcutaneous tissue disorders urticaria	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose
Social circumstances homicide	0.68% 1/147 • Number of events 1 • pre-dose to 28 days (+/-2 days) post dose

Other adverse events

Other adverse events
Measure	Treatment n=147 participants at risk DX-88 (ecallantide)
Congenital, familial and genetic disorders hereditary angioedema	17.0% 25/147 • Number of events 25 • pre-dose to 28 days (+/-2 days) post dose
Gastrointestinal disorders nausea	12.9% 19/147 • Number of events 19 • pre-dose to 28 days (+/-2 days) post dose
Nervous system disorders headache	10.9% 16/147 • Number of events 16 • pre-dose to 28 days (+/-2 days) post dose
Gastrointestinal disorders abdominal pain	8.2% 12/147 • Number of events 12 • pre-dose to 28 days (+/-2 days) post dose
Respiratory, thoracic and mediastinal disorders upper respiratory tract infection	7.5% 11/147 • Number of events 11 • pre-dose to 28 days (+/-2 days) post dose
Gastrointestinal disorders vomiting	6.8% 10/147 • Number of events 10 • pre-dose to 28 days (+/-2 days) post dose
Gastrointestinal disorders diarrhoea	6.1% 9/147 • Number of events 9 • pre-dose to 28 days (+/-2 days) post dose
Psychiatric disorders anxiety	5.4% 8/147 • Number of events 8 • pre-dose to 28 days (+/-2 days) post dose

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

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