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

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)

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.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: DX-2930 - 300mg/2wk; Drug: DX-2930 - 300mg/4wk; Drug: DX-2930 - 150mg/4wk; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1G 6C6
      • Ottawa Allergy Research Corporation
    • Toronto, Ontario, Canada, M4V 1R2
      • Gordon Sussman Clinical Research Inc.
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4M6
      • Clinique Specialisee en Allergie de la Capitale
• Germany
  • Berlin, Germany, 10117
    • Charité - University of Berlin
  • Mainz, Germany, 55131
    • Hautklinik und Poliklinik der Universitätsmedizin
  • Morfelden-Walldorf, Germany, 64546
    • HZRM Hämophilie-Zentrum Rhein Main
• Italy
  • Milan, Italy, 20157
    • Hospital L. Sacco, Milan University
• Jordan
  • Amman, Jordan, 11941
    • Triumpharma
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Sociedad Alergologica
• United Kingdom
  • London, United Kingdom, E1 2ES
    • Barts Health NHS Trust Clinical Research Centre
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Clinical Research Center of Alabama, LLC
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Medical Research of Arizona
  • California
    • San Diego, California, United States, 92122
      • UC San Diego School of Medicine
    • Santa Monica, California, United States, 90404
      • AIRE Medical of Los Angeles
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Clinical Research
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe International Health & Research Centers
    • Colorado Springs, Colorado, United States, 80907
      • Asthma and Allergy Associates, P.C.
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University Of Kansas Medical Center
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute of Asthma & Allergy, P.C.
  • Massachusetts
    • Boston, Massachusetts, United States, 02421
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • University of Michigan Hospital and Health System
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Midwest Immunology Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Belleville, New Jersey, United States, 07109
      • Hudson-Essex Allergy, LLC
    • Ocean City, New Jersey, United States, 07712
      • Atlantic Research Center, LLC
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10029
      • The Mount Sinai Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • American Health Research
    • Durham, North Carolina, United States, 27705
      • Duke Asthma, Allergy and Airway Center
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Bernstein Clinical Research Center, LLC
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LTD
    • Toledo, Ohio, United States, 43617
      • Toledo Institute of Clinical Research
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • Texas
    • Austin, Texas, United States, 78731
      • Austin Regional Clinic
    • Dallas, Texas, United States, 75231
      • AARA Research Center
  • Utah
    • Draper, Utah, United States, 84020
      • Intermountain Clinical Research
    • Murray, Utah, United States, 84107
      • Allergy Associates of Utah
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University
  • Washington
    • Spokane, Washington, United States, 99202
      • Marycliff Allergy Specialists
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DX-2930 300 mg every 2 weeks; 300 mg DX-2930 administered every 2 weeks by subcutaneous injection.	Drug: DX-2930 - 300mg/2wk; 300 mg DX-2930 administered every 2 weeks by subcutaneous injection.
Experimental: DX-2930 300 mg every 4 weeks; 300 mg DX-2930 administered every 4 weeks by subcutaneous injection	Drug: 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.
Experimental: DX-2930 150 mg every 4 weeks; 150 mg DX-2930 administered every 4 weeks by subcutaneous injection	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 Comparator: Placebo; Placebo administered every 2 weeks by subcutaneous injection.	Drug: Placebo; Placebo administered every 2 weeks by subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Shire
• Collaborators: Dyax Corp.
• Investigators: Study Director: Shire Physician, Shire

Publications and helpful links

General Publications

• Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
• Craig TJ, Zaragoza-Urdaz RH, Li HH, Yu M, Ren H, Juethner S, Anderson J; HELP and HELP OLE Study Investigators. Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies. Allergy Asthma Clin Immunol. 2022 Sep 24;18(1):85. doi: 10.1186/s13223-022-00721-y.
• Banerji A, Riedl MA, Bernstein JA, Cicardi M, Longhurst HJ, Zuraw BL, Busse PJ, Anderson J, Magerl M, Martinez-Saguer I, Davis-Lorton M, Zanichelli A, Li HH, Craig T, Jacobs J, Johnston DT, Shapiro R, Yang WH, Lumry WR, Manning ME, Schwartz LB, Shennak M, Soteres D, Zaragoza-Urdaz RH, Gierer S, Smith AM, Tachdjian R, Wedner HJ, Hebert J, Rehman SM, Staubach P, Schranz J, Baptista J, Nothaft W, Maurer M; HELP Investigators. Effect of Lanadelumab Compared With Placebo on Prevention of Hereditary Angioedema Attacks: A Randomized Clinical Trial. JAMA. 2018 Nov 27;320(20):2108-2121. doi: 10.1001/jama.2018.16773. Erratum In: JAMA. 2019 Apr 23;321(16):1636.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2016
• Primary Completion (Actual): April 13, 2017
• Study Completion (Actual): April 13, 2017

Study Registration Dates

• First Submitted: October 23, 2015
• First Submitted That Met QC Criteria: October 23, 2015
• First Posted (Estimate): October 26, 2015

Study Record Updates

• Last Update Posted (Actual): June 2, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Hereditary Angioedema; DX-2930; Dyax
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: DX-2930-03; 2015-003943-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)