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

This study has been completed.
Sponsor:
Information provided by:
Dyax Corp.
ClinicalTrials.gov Identifier:
NCT00457015
First received: April 4, 2007
Last updated: April 9, 2010
Last verified: April 2010
  Purpose

The purpose of this study is to evaluate the efficacy and safety of DX-88 (ecallantide) versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema.


Condition Intervention Phase
Hereditary Angioedema
Drug: ecallantide
Drug: Phosphate Buffer Saline (PBS), pH 7.0
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: EDEMA4: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of DX-88 (Ecallantide) for the Treatment of Acute Attacks of Hereditary Angioedema

Resource links provided by NLM:


Further study details as provided by Dyax Corp.:

Primary Outcome Measures:
  • Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose [ Time Frame: baseline, 4 hours post-dose ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Treatment Outcome Score at 4 Hours Post-Dose [ Time Frame: 4 hours post-dose ] [ Designated as safety issue: No ]
    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.

  • Patients With Significant Improvement in Overall Response [ Time Frame: 4 hours post-dose ] [ Designated as safety issue: No ]
    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 resposne assessment as "a lot better or resolved."

  • Patients With a Successful Response at 4 Hours Post-dosing, Based on the Change From Baseline in the MSCS Score [ Time Frame: baseline, 4 hours post-dosing ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients Maintaining a Significant Improvement in Overall Response Through 24 Hours [ Time Frame: 24 hours post-dosing ] [ Designated as safety issue: No ]
    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".


Enrollment: 96
Study Start Date: April 2007
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DX-88 (ecallantide)
DX-88 (ecallantide) 30 mg given as three 10 mg/mL subcutaneous injections.
Drug: ecallantide
dose of 30 mg (10 mg/ml) given as 3 subcutaneous injections.
Other Name: DX-88
Placebo Comparator: Placebo
Placebo, Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.
Drug: Phosphate Buffer Saline (PBS), pH 7.0
given as three 1mL subcutaneous injections.

Detailed Description:

This is a randomized placebo-controlled trial.

The study is designed to assess the efficacy and safety of 30 mg subcutaneous ecallantide versus placebo in the treatment of moderate to severe acute attacks of hereditary angioedema. This study is conducted under Special Protocol Assessment with the FDA and is designed to provide pivotal efficacy data on 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.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 10 years of age or older
  • Executed informed consent
  • Documented diagnosis of HAE (Type I or II)
  • Presentation at the site within 8 hours of patient recognition of an moderate to severe HAE acute attack

Exclusion Criteria:

  • Receipt of an investigational drug or device, within 30 days prior to study treatment
  • Receipt of non-investigational C1-INH within 7 days of treatment
  • Receipt of DX-88 (ecallantide) within 3 days prior to study treatment
  • Diagnosis of acquired angioedema (AAE), estrogen-dependent angioedema or drug-induced angioedema (including angiotensin-converting enzyme inhibitor induced angioedema)
  • Pregnancy or breastfeeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00457015

  Show 45 Study Locations
Sponsors and Collaborators
Dyax Corp.
Investigators
Study Director: Patrick Horn, MD, PhD Dyax Corp.
  More Information

No publications provided by Dyax Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bill Pullman, MD, PhD, Executive Vice President, Chief Development Officer, Dyax Corp.
ClinicalTrials.gov Identifier: NCT00457015     History of Changes
Other Study ID Numbers: EDEMA4 (DX-88/20)
Study First Received: April 4, 2007
Results First Received: December 30, 2009
Last Updated: April 9, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Angioedemas, Hereditary
Angioedema
Cardiovascular Diseases
Genetic Diseases, Inborn
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Skin Diseases
Skin Diseases, Vascular
Urticaria
Vascular Diseases

ClinicalTrials.gov processed this record on October 22, 2014