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Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema (HAE) Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT02093923
First received: March 17, 2014
Last updated: June 20, 2016
Last verified: June 2016
  Purpose
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of multiple subcutaneous administrations of DX-2930 across a range of doses in Hereditary Angioedema subjects.

Condition Intervention Phase
Hereditary Angioedema
Drug: DX-2930
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1b, Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Subjects

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Number of Patients With Treatment-Emergent Adverse Events (TEAE) [ Time Frame: through 4 months ] [ Designated as safety issue: Yes ]
    As per the DX-2930-02 clinical protocol, an AE was considered treatment-emergent if the onset time was after administration of study drug through the Day 120 post-dose final follow-up visit or, in the event that onset time preceded study drug administration, the AE increased in severity during the 120-day post-dose follow-up period.

  • Proportion of Patients With Treatment-Emergent Adverse Events (TEAE) [ Time Frame: through 4 months ] [ Designated as safety issue: Yes ]
    As per the DX-2930-02 clinical protocol, an AE was considered treatment-emergent if the onset time was after administration of study drug through the Day 120 post-dose final follow-up visit or, in the event that onset time preceded study drug administration, the AE increased in severity during the 120-day post-dose follow-up period.

  • Number of Patients With Serious Adverse Events (SAEs) [ Time Frame: through 4 months ] [ Designated as safety issue: Yes ]

    As per the DX-2930-02 clinical protocol, a SAE was any adverse experience occurring at any dose that resulted in any of the following outcomes:

    • Death
    • Life-threatening experience: "life-threatening" referred to a situation in which the subject was at risk of death at the time of the event, it did not refer to an event that might have caused death if it were more severe.
    • Required inpatient hospitalization or prolongation of existing hospitalization: this did not include hospitalization for observation with release within 24 hours. A scheduled hospitalization for a pre-existing condition that had not worsened during participation in the study did not meet this criterion. Pre-planned hospitalizations for an elective medical/surgical procedure or routine check-ups did not meet this criterion.
    • Resulted in persistent or significant disability or incapacity.
    • Was a congenital anomaly or birth defect.
    • Was considered to be an important medical event

  • Proportion of Patients With Serious Adverse Events [ Time Frame: through 4 months ] [ Designated as safety issue: Yes ]

    As per the DX-2930-02 clinical protocol, a SAE was any adverse experience occurring at any dose that resulted in any of the following outcomes:

    • Death
    • Life-threatening experience: "life-threatening" referred to a situation in which the subject was at risk of death at the time of the event, it did not refer to an event that might have caused death if it were more severe.
    • Required inpatient hospitalization or prolongation of existing hospitalization: this did not include hospitalization for observation with release within 24 hours. A scheduled hospitalization for a pre-existing condition that had not worsened during participation in the study did not meet this criterion. Pre-planned hospitalizations for an elective medical/surgical procedure or routine check-ups did not meet this criterion.
    • Resulted in persistent or significant disability or incapacity.
    • Was a congenital anomaly or birth defect.
    • Was considered to be an important medical event


Secondary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) [ Time Frame: Pharmacokinetic samples were drawn on Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120. ] [ Designated as safety issue: No ]
  • Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Pharmacokinetic samples were drawn on Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120. ] [ Designated as safety issue: No ]
  • Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: Pharmacokinetic samples were drawn on Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120. ] [ Designated as safety issue: No ]
  • Apparent Clearance (CL/F) [ Time Frame: Pharmacokinetic samples were drawn on Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120. ] [ Designated as safety issue: No ]
  • Apparent Volume of Distribution (Vd/F) [ Time Frame: Pharmacokinetic samples were drawn on Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120. ] [ Designated as safety issue: No ]
  • Terminal Elimination Half-life (t1/2) [ Time Frame: Pharmacokinetic samples were drawn on Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120. ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • HAE Attack Rate Per Week [ Time Frame: Baseline, Day 8 to Day 50 ] [ Designated as safety issue: No ]
    The pre-specified, primary efficacy analysis was based on subjects in the 300 mg, 400 mg, and placebo dose groups with a historical baseline attack rate of at least 2 attacks over the last 3 months prior to enrollment. The result is based on General Estimating Equation (GEE) analysis of repeated counts per week during the prespecified assessment period (Days 8 to 50; predicted to correspond to a period of notable drug exposure). Baseline HAE attack rate per week is a covariate, treatment group is a fixed effect, and subject is a random effect in the GEE model with independence working correlation structure.


Enrollment: 38
Study Start Date: April 2014
Study Completion Date: May 2015
Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DX-2930, Dose level 1
30 mg of DX-2930 administered twice, two weeks apart
Drug: DX-2930
DX-2930 is a recombinant, Chinese hamster ovary (CHO) cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody
Drug: Placebo
Placebo
Experimental: DX-2930, Dose level 2
100 mg of DX-2930 administered twice, two weeks apart
Drug: DX-2930
DX-2930 is a recombinant, Chinese hamster ovary (CHO) cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody
Drug: Placebo
Placebo
Experimental: DX-2930, Dose level 3
300 mg of DX-2930 administered twice, two weeks apart
Drug: DX-2930
DX-2930 is a recombinant, Chinese hamster ovary (CHO) cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody
Drug: Placebo
Placebo
Experimental: DX-2930, Dose level 4
400 mg of DX-2930 administered twice, two weeks apart
Drug: DX-2930
DX-2930 is a recombinant, Chinese hamster ovary (CHO) cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody
Drug: Placebo
Placebo
Placebo Comparator: Placebo
Placebo administered twice, two weeks apart
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 18 years of age at the time of screening.
  • Documented diagnosis of HAE (Type I or II)
  • Experiencing ≥2 HAE attacks per year, with at least 1 attack in the past 6 months reported by the subject.
  • Willing and able to read, understand, and sign an informed consent form.
  • Females of childbearing potential must agree to be abstinent or else use acceptable forms of contraception throughout study
  • Males with female partners of childbearing potential must agree to be abstinent or use a medically acceptable form of contraception throughout study.

Exclusion Criteria:

  • Exposure to an investigational drug or device within 90 days prior to study.
  • History of exposure within the past 5 years to a monoclonal antibody or recombinant protein bearing an Fc domain.
  • Concomitant diagnosis of another form of chronic angioedema
  • Use of long-term prophylaxis for HAE within 90 days prior to study.
  • Use of C1-INH that exceeds a total of 30 days within the past 90 days prior to study; any use of C1-INH within 7 days prior to study.
  • Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 90 days prior to study.
  • Exposure to androgens within 90 days prior to study.
  • Presence of an indwelling catheter.
  • Diagnosis of HIV.
  • Active liver disease or liver function test abnormalities
  • History of substance abuse or dependence.
  • Pregnancy or breastfeeding.
  • Any condition that, in the opinion of the Investigator, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results
  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: NCT02093923

Locations
United States, California
UC San Diego Health System - La Jolla
San Diego, California, United States, 92122
Allergy & Asthma Clinical Research
Walnut Creek, California, United States, 94598
United States, Florida
University of South Florida Asthma, Allergy or Immunology Clinical Research Unit
Tampa, Florida, United States, 33613
United States, Maryland
Institute for Asthma & Allergy, PC
Chevy Chase, Maryland, United States, 20815
United States, Massachusetts
Massachusetts General Hospital Allergy Associates
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Winthrop-University Hospital, Clinical Trials Center
Mineola, New York, United States, 11501
Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
New York, New York, United States, 10029
United States, Ohio
UC Physicians Company
Cincinnati, Ohio, United States, 45267
United States, Oregon
Baker Allergy, Asthma and Dermatology Research Center
Lake Oswego, Oregon, United States, 97035
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
United States, Texas
AARA Research Center
Dallas, Texas, United States, 75231
Italy
Ospedale L. Sacco
Milano, MI, Italy, 20157
Jordan
Jordan University Hospital
Amman, Jordan, 11942
Sponsors and Collaborators
Shire
  More Information

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02093923     History of Changes
Other Study ID Numbers: DX-2930-02 
Study First Received: March 17, 2014
Results First Received: April 20, 2016
Last Updated: June 20, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire:
HAE

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

ClinicalTrials.gov processed this record on December 09, 2016