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

• ClinicalTrials.gov Identifier: NCT00262080
• Recruitment Status: Completed
• First Posted: December 6, 2005
• Results First Posted: May 11, 2010
• Last Update Posted: September 19, 2016
• Sponsor: Shire
• Information provided by: Shire

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.

Condition or disease	Intervention/treatment	Phase
Hereditary Angioedema (HAE)	Drug: ecallantide; Drug: Phosphate Buffer Saline (PBS),	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: December 2005
• Actual Primary Completion Date: December 2005
• Actual Study Completion Date: February 2007

Arms and Interventions

Arm	Intervention/treatment
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; Phosphate Buffer Saline (PBS), pH 7.0 given as 3 subcutaneous injections.	Drug: Phosphate Buffer Saline (PBS),; given as three 1mL subcutaneous injections.

Outcome Measures

Primary Outcome Measures :

1. Treatment Outcome Score at 4 Hours Post-Dose [ Time Frame: 4 hours post-dose (DOUBLE-BLIND PART) ]
   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 :

1. Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose [ Time Frame: baseline, 4 hours post-dose (DOUBLE-BLIND PART) ]
   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.
2. Time to Significant Improvement in Overall Response [ Time Frame: 4 hours post-dose (DOUBLE-BLIND PART) ]
   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".

Other Outcome Measures:

1. Number of Patients With Symptom Complexes of Treated Attack at Baseline(DOUBLE-BLIND PART) [ Time Frame: Baseline ]
   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
2. Treatment Outcome Score at 4 Hours Post-Dose Over Multiple Treatment Episodes [ Time Frame: 4 hours post-dose (REPEAT-DOSING PART) ]
   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.
3. Change From Baseline in Mean Symptom Complex Severity (MSCS) Score at 4 Hours Post-dose Over Multiple Treatment Episodes [ Time Frame: baseline, 4 hours post-dose (REPEAT-DOSING PART) ]
   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.
4. Time to Significant Improvement in Overall Response Over Multiple Treatment Episodes [ Time Frame: 4 hours post-dose (REPEAT-DOSING PART) ]
   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)

Eligibility Criteria

• Ages Eligible for Study: 10 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Maryland

Institute for Asthma and Allergy

Wheaton, Maryland, United States, 20902

Sponsors and Collaborators

Shire

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

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.

• Responsible Party: Bill Pullman, MD, PhD, Executive Vice President, Chief Development Officer, Dyax Corp.
• ClinicalTrials.gov Identifier: NCT00262080 History of Changes
• Other Study ID Numbers: EDEMA3 (DX-88/14)
• First Posted: December 6, 2005
• Results First Posted: May 11, 2010
• Last Update Posted: September 19, 2016
• Last Verified: August 2016

Additional relevant MeSH terms:

Angioedema; Angioedemas, Hereditary; Ecallantide; Vascular Diseases; Cardiovascular Diseases; Urticaria; Skin Diseases, Vascular; Skin Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Genetic Diseases, Inborn; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents