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

Primary Purpose

Hereditary Angioedema (HAE)

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
ecallantide
Phosphate Buffer Saline (PBS),
Sponsored by
Shire
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hereditary Angioedema (HAE)

Eligibility Criteria

10 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 10 and older Documented diagnosis of HAE, Type I or II Executed informed consent Presentation for treatment within 8 hours of patient recognition of moderate to severe HAE attack Exclusion Criteria: Receipt of investigational drug or device, other than DX-88, within 30 days of treatment Receipt of non-investigational C1-INH (C1 esterase inhibitor) within 7 days of treatment Diagnostic of acquired angioedema, estrogen-dependent angioedema or drug induced angioedema Pregnancy or breastfeeding Patients who have received DX-88 within 7 days of presentation for dosing in the Double-blind Phase

Sites / Locations

  • Institute for Asthma and Allergy

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

DX-88 (ecallantide)

Placebo

Arm Description

DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections.

Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.

Outcomes

Primary Outcome Measures

Treatment Outcome Score at 4 Hours Post-Dose
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] to significant worsening [-100]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.

Secondary Outcome Measures

Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
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 (minimally important difference) was indicated by a reduction in the score of 0.30 or more.
Time to Significant Improvement in Overall Response
The overall response assessment is a patient-reported assessment of global response to therapy. Patients are asked to perform an overall response assessment at regular intervals, relative to baseline. Patients were asked "overall how are you feeling" compared to how they felt before study drug. Answer options were "a lot worse", "a little worse", "same", "a little better" or "a lot better or resolved". Significant improvement was the first time that the patient responded to the assessment as "a little better or resolved".

Full Information

First Posted
December 5, 2005
Last Updated
June 3, 2021
Sponsor
Shire
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1. Study Identification

Unique Protocol Identification Number
NCT00262080
Brief Title
Efficacy and Safety Study of DX-88 to Treat Acute Attacks of Hereditary Angioedema (HAE)
Official Title
A Double-blind, Placebo-controlled Study (72 Patients, Randomized 1:1) Followed by a Repeat-dosing Phase to Assess the Efficacy and Safety of DX-88 (Ecallantide; Recombinant Plasma Kallikrein Inhibitor) for the Treatment of Acute Attacks of Hereditary Angioedema
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
December 31, 2005 (Actual)
Primary Completion Date
December 31, 2005 (Actual)
Study Completion Date
February 28, 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to determine if a subcutaneous dose of DX-88 (ecallantide; an investigational product) is safe and relieves symptoms of HAE in patients suffering from moderate to severe acute attacks of HAE.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema (HAE)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
DX-88 (ecallantide)
Arm Type
Experimental
Arm Description
DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
Intervention Type
Drug
Intervention Name(s)
ecallantide
Other Intervention Name(s)
DX-88
Intervention Description
dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections.
Intervention Type
Drug
Intervention Name(s)
Phosphate Buffer Saline (PBS),
Intervention Description
given as three 1mL subcutaneous injections.
Primary Outcome Measure Information:
Title
Treatment Outcome Score at 4 Hours Post-Dose
Description
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] to significant worsening [-100]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.
Time Frame
4 hours post-dose (DOUBLE-BLIND PART)
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose
Description
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 (minimally important difference) was indicated by a reduction in the score of 0.30 or more.
Time Frame
baseline, 4 hours post-dose (DOUBLE-BLIND PART)
Title
Time to Significant Improvement in Overall Response
Description
The overall response assessment is a patient-reported assessment of global response to therapy. Patients are asked to perform an overall response assessment at regular intervals, relative to baseline. Patients were asked "overall how are you feeling" compared to how they felt before study drug. Answer options were "a lot worse", "a little worse", "same", "a little better" or "a lot better or resolved". Significant improvement was the first time that the patient responded to the assessment as "a little better or resolved".
Time Frame
4 hours post-dose (DOUBLE-BLIND PART)
Other Pre-specified Outcome Measures:
Title
Number of Patients With Symptom Complexes of Treated Attack at Baseline(DOUBLE-BLIND PART)
Description
Patient-reported severity of symptom complexes at baseline, by symptom complex and treatment group. Patients were to have at least one symptom complex that was moderate or severe. Patients could present with multiple symptom complexes, some of which could be mild. Mild=noticeable but do not impact daily living activities; Moderate=treatment or intervention is highly desirable and activities of daily living are impacted; Severe=require treatment or intervention due to inability to perform activities of daily living. The results are for number of patients with symptom complexes including mild, moderate and severe, provided the patients have at least one symptom complex that was moderate or severe
Time Frame
Baseline
Title
Treatment Outcome Score at 4 Hours Post-Dose Over Multiple Treatment Episodes
Description
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] to significant worsening [-100]). The response at each anatomic site was weighted by baseline severity and then the weighted scores across all involved sites were averaged to calculate the TOS. Clinically meaningful improvement was indicated by a TOS of 30 or higher.
Time Frame
4 hours post-dose (REPEAT-DOSING PART)
Title
Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose Over Multiple Treatment Episodes
Description
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.
Time Frame
baseline, 4 hours post-dose (REPEAT-DOSING PART)
Title
Time to Significant Improvement in Overall Response Over Multiple Treatment Episodes
Description
The overall response assessment is a patient-reported assessment of global response to therapy. Patients are asked to perform an overall response assessment at regular intervals, relative to baseline (ie,immediately before treatment) using the following 5-category scale from significant improvement (Score = 100)to significant worsening (Score = -100)
Time Frame
4 hours post-dose (REPEAT-DOSING PART)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 10 and older Documented diagnosis of HAE, Type I or II Executed informed consent Presentation for treatment within 8 hours of patient recognition of moderate to severe HAE attack Exclusion Criteria: Receipt of investigational drug or device, other than DX-88, within 30 days of treatment Receipt of non-investigational C1-INH (C1 esterase inhibitor) within 7 days of treatment Diagnostic of acquired angioedema, estrogen-dependent angioedema or drug induced angioedema Pregnancy or breastfeeding Patients who have received DX-88 within 7 days of presentation for dosing in the Double-blind Phase
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Institute for Asthma and Allergy
City
Wheaton
State/Province
Maryland
ZIP/Postal Code
20902
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24712435
Citation
Rubinstein E, Stolz LE, Sheffer AL, Stevens C, Bousvaros A. Abdominal attacks and treatment in hereditary angioedema with C1-inhibitor deficiency. BMC Gastroenterol. 2014 Apr 9;14:71. doi: 10.1186/1471-230X-14-71.
Results Reference
derived
PubMed Identifier
23878046
Citation
MacGinnitie AJ, Davis-Lorton M, Stolz LE, Tachdjian R. Use of ecallantide in pediatric hereditary angioedema. Pediatrics. 2013 Aug;132(2):e490-7. doi: 10.1542/peds.2013-0646. Epub 2013 Jul 22.
Results Reference
derived
PubMed Identifier
23548529
Citation
Sheffer AL, MacGinnitie AJ, Campion M, Stolz LE, Pullman WE. Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013 Mar;110(3):184-188.e2. doi: 10.1016/j.anai.2012.12.007. Epub 2013 Jan 5.
Results Reference
derived
PubMed Identifier
22765833
Citation
Bernstein JA, Shea EP, Koester J, Iarrobino R, Pullman WE. Assessment of rebound and relapse following ecallantide treatment for acute attacks of hereditary angioedema. Allergy. 2012 Sep;67(9):1173-80. doi: 10.1111/j.1398-9995.2012.02864.x. Epub 2012 Jul 5.
Results Reference
derived
PubMed Identifier
21130380
Citation
Riedl M, Campion M, Horn PT, Pullman WE. Response time for ecallantide treatment of acute hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2010 Dec;105(6):430-436.e2. doi: 10.1016/j.anai.2010.09.005. Epub 2010 Oct 25.
Results Reference
derived
PubMed Identifier
20818887
Citation
Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, Horn PT, Pullman WE. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):523-31. doi: 10.1056/NEJMoa0905079.
Results Reference
derived

Learn more about this trial

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

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