Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02586805
Recruitment Status : Completed
First Posted : October 26, 2015
Results First Posted : April 24, 2018
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
Dyax Corp.
Information provided by (Responsible Party):
Shire

Tracking Information
First Submitted Date  ICMJE October 23, 2015
First Posted Date  ICMJE October 26, 2015
Results First Submitted Date  ICMJE March 20, 2018
Results First Posted Date  ICMJE April 24, 2018
Last Update Posted Date April 16, 2019
Actual Study Start Date  ICMJE March 3, 2016
Actual Primary Completion Date April 13, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During Treatment Period [ Time Frame: From Day 0 to 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 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
Number of HAE attacks per week observed in each DX-2930 treatment arm versus placebo arm [ Time Frame: Efficacy assessment period (Day 14 through Day 182) ]
Change History Complete list of historical versions of study NCT02586805 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2018)
  • Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attack Requiring Acute Treatment [ Time Frame: From Day 0 to 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 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.
  • Rate of Moderate or Severe Investigator Confirmed Hereditary Angioedema (HAE) Attacks [ Time Frame: From Day 0 to Day 182 ]
    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.
  • Rate of Investigator Confirmed Hereditary Angioedema (HAE) Attacks During Day 14 Through Day 182 [ Time Frame: From Day 14 to 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
  • Time to first HAE attack for each DX-2930 treatment arm versus placebo arm [ Time Frame: Efficacy assessment period (Day 14 through Day 182) ]
  • Number per week of HAE attacks requiring acute attack therapy use for each DX-2930 treatment arm versus placebo arm [ Time Frame: Efficacy assessment period (Day 14 through Day 182) ]
  • Number per week of moderate or severe HAE attacks for each DX-2930 treatment arm versus placebo arm [ Time Frame: Efficacy assessment period (Day 14 through Day 182) ]
  • Reduction in high-morbidity HAE attacks for each DX-2930 treatment arm versus placebo arm [ Time Frame: Efficacy assessment period (Day 14 through Day 182) ]
    A high-morbidity HAE attack is defined as any attack that has at least one of the following characteristics: severe, results in hospitalization (except hospitalization for observation <24 hours), hemodynamically significant (systolic blood pressure < 90, requires IV hydration, or associated with syncope or near-syncope) or laryngeal.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of DX-2930 to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE
Official Title  ICMJE 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)
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Hereditary Angioedema (HAE)
Intervention  ICMJE
  • Drug: DX-2930 - 300mg/2wk
    300 mg DX-2930 administered every 2 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.
  • 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.
  • Drug: Placebo
    Placebo administered every 2 weeks by subcutaneous injection.
Study Arms  ICMJE
  • Experimental: DX-2930 300 mg every 2 weeks
    300 mg DX-2930 administered every 2 weeks by subcutaneous injection.
    Intervention: Drug: DX-2930 - 300mg/2wk
  • Experimental: DX-2930 300 mg every 4 weeks
    300 mg DX-2930 administered every 4 weeks by subcutaneous injection
    Intervention: Drug: DX-2930 - 300mg/4wk
  • Experimental: DX-2930 150 mg every 4 weeks
    150 mg DX-2930 administered every 4 weeks by subcutaneous injection
    Intervention: Drug: DX-2930 - 150mg/4wk
  • Placebo Comparator: Placebo
    Placebo administered every 2 weeks by subcutaneous injection.
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 19, 2018)
125
Original Estimated Enrollment  ICMJE
 (submitted: October 23, 2015)
108
Actual Study Completion Date  ICMJE April 13, 2017
Actual Primary Completion Date April 13, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Italy,   Jordan,   Puerto Rico,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02586805
Other Study ID Numbers  ICMJE DX-2930-03
2015-003943-20 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Shire provides access to the de-identified individual participant data for eligible studies to aid qualified researchers in addressing legitimate scientific objectives. These IPDs will be provided following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.shiretrials.com website. 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.
URL: https://www.shiretrials.com/en/our-commitment-to-transparency/data-sharing-with-researchers
Responsible Party Shire
Study Sponsor  ICMJE Shire
Collaborators  ICMJE Dyax Corp.
Investigators  ICMJE
Study Director: Shire Physician Shire
PRS Account Shire
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP