Efficacy and Safety Study of DX-2930 to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE

Hereditary Angioedema (HAE) Clinical Trial

Official title:

HELP Study: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study to Evaluate DX-2930 For Long-Term Prophylaxis Against Acute Attacks of Hereditary Angioedema (HAE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02586805
• Other study ID #: DX-2930-03
• Secondary ID: 2015-003943-20
• Status: Completed
• Phase: Phase 3
• Start date: March 3, 2016
• Est. completion date: April 13, 2017

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of DX-2930 in preventing acute angioedema attacks in patients with Type I and Type II HAE.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: April 13, 2017
• Est. primary completion date: April 13, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Males and females 12 years of age or older at time of screening

• Documented diagnosis of HAE, Type I or II

• Baseline rate of at least 1 Investigator-confirmed HAE attack per 4 weeks

• Adult subjects and caregivers of subjects under the age of 18 are willing and able to read, understand, and sign an informed consent form. Subjects age 12 to 17, whose caregiver provides informed consent, are willing and able to read, understand an dsign an assent form.

• Males and femailes who are fertile and sexually active must adhere to contraception requirements.

Exclusion Criteria:

• Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema, idiopathic angioedema, or recurrent angioedema associated with urticaria.

• Participation in a prior DX-2930 study

• Treatment with any other investigational drug or exposure to an investigational device within 4 weeks prior screening

• Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications within 4 weeks prior to screening.

• Exposure to androgens within 2 weeks prior to entering the run-in period.

• Use of long-term prophylactic therapy for HAE within 2 weeks prior to entering the run-in period.

• Use of short-term prophylaxis for HAE within 7 days prior to entering the run-in period.

• Any of the following liver function test abnormalities: alanine aminotransferase (ALT) > 3x upper limit of normal, or aspartate aminotransferase (AST) > 3x upper limit of normal, or total bilirubin > 2x upper limit of normal (unless the bilirubin elevation is a result of Gilbert's syndrome).

• Pregnancy or breastfeeding.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema (HAE)

Intervention

Drug:
• DX-2930 - 300mg/2wk
300 mg DX-2930 administered every 2 weeks by subcutaneous injection.
• DX-2930 - 300mg/4wk
300 mg DX-2930 administered every 4 weeks by subcutaneous injection. To maintain the study blind, subjects will be given placebo injections every other 2 weeks when they are not receiving drug.
• DX-2930 - 150mg/4wk
150 mg DX-2930 administered every 4 weeks by subcutaneous injection. To maintain the study blind, subjects will be given placebo injections every other 2 weeks when they are not receiving drug.
• Placebo
Placebo administered every 2 weeks by subcutaneous injection.

Locations

Country	Name	City	State
Canada	Ottawa Allergy Research Corporation	Ottawa	Ontario
Canada	Clinique Specialisee en Allergie de la Capitale	Quebec City	Quebec
Canada	Gordon Sussman Clinical Research Inc.	Toronto	Ontario
Germany	Charité - University of Berlin	Berlin
Germany	Hautklinik und Poliklinik der Universitätsmedizin	Mainz
Germany	HZRM Hamophilie-Zentrum Rhein Main	Morfelden-Walldorf
Italy	Hospital L. Sacco, Milan University	Milan
Jordan	Triumpharma	Amman
Puerto Rico	Sociedad Alergologica	San Juan
United Kingdom	Barts Health NHS Trust Clinical Research Centre	London
United States	University of Michigan Hospital and Health System	Ann Arbor	Michigan
United States	Austin Regional Clinic	Austin	Texas
United States	Hudson-Essex Allergy, LLC	Belleville	New Jersey
United States	Clinical Research Center of Alabama, LLC	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	IMMUNOe International Health & Research Centers	Centennial	Colorado
United States	American Health Research	Charlotte	North Carolina
United States	Institute of Asthma & Allergy, P.C.	Chevy Chase	Maryland
United States	Bernstein Clinical Research Center, LLC	Cincinnati	Ohio
United States	Asthma and Allergy Associates, P.C.	Colorado Springs	Colorado
United States	Optimed Research, LTD	Columbus	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Intermountain Clinical Research	Draper	Utah
United States	Duke Asthma, Allergy and Airway Center	Durham	North Carolina
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Winthrop University Hospital	Mineola	New York
United States	Allergy Associates of Utah	Murray	Utah
United States	The Mount Sinai Medical Center	New York	New York
United States	Atlantic Research Center, LLC	Ocean City	New Jersey
United States	Midwest Immunology Clinic	Plymouth	Minnesota
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UC San Diego School of Medicine	San Diego	California
United States	AIRE Medical of Los Angeles	Santa Monica	California
United States	Medical Research of Arizona	Scottsdale	Arizona
United States	Marycliff Allergy Specialists	Spokane	Washington
United States	University of South Florida	Tampa	Florida
United States	Toledo Institute of Clinical Research	Toledo	Ohio
United States	Allergy & Asthma Clinical Research	Walnut Creek	California

Sponsors (2)

Lead Sponsor	Collaborator
Shire	Dyax Corp.

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Italy,  Jordan,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During Treatment Period	HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Rate of investigator confirmed HAE attacks was analyzed using a generalized linear model (GLM) for count data assuming a poisson distribution with a log link function and Pearson chi-square scaling of standard errors to account for potential overdispersion. The logarithm of time in days each subject was observed during the treatment period was used as an offset variable in the model.	From Day 0 to Day 182
Secondary	Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attack Requiring Acute Treatment	HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Rate of investigator confirmed HAE attack was analyzed using the GLM for count data assuming a poisson distribution with a log link function and Pearson chi-square scaling of standard errors to account for potential overdispersion. The logarithm of time in days each subject was observed during the treatment period was used as an offset variable in the model.	From Day 0 to Day 182
Secondary	Rate of Moderate or Severe Investigator Confirmed Hereditary Angioedema (HAE) Attacks	HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Moderate and severe investigator-confirmed HAE attacks were the attacks that were moderate or severe as per the HAE attack assessment and reporting procedures (HAARP) defined severity. The overall severity of attack was determined by the investigator using following definitions: mild (transient or mild discomfort), moderate (mild to moderate limitation in activity), severe (marked limitation in activity). Rate of moderate or severe investigator confirmed HAE attack was analyzed using the GLM for count data assuming a poisson distribution with a log link function and Pearson chi-square scaling of standard errors to account for potential overdispersion. The logarithm of time in days each subject was observed during the treatment period was used as an offset variable in the model.	From Day 0 to Day 182
Secondary	Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During Day 14 Through Day 182	HAE attack was defined as a discrete episode during which the participant progressed from no angioedema to symptoms of angioedema. Rate of investigator confirmed HAE attacks during day 14 after study drug administration through day 182 was analyzed by the same poisson regression model as in the primary endpoint analysis.	From Day 14 to Day 182