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A Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Participants

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: NCT02093923
Recruitment Status : Completed
First Posted : March 21, 2014
Results First Posted : August 1, 2016
Last Update Posted : May 27, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Shire )

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) profile of multiple subcutaneous administrations of DX-2930 across a range of doses in HAE participants.

Condition or disease Intervention/treatment Phase
Hereditary Angioedema (HAE) Drug: DX-2930 Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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
Actual Study Start Date : May 14, 2014
Actual Primary Completion Date : May 18, 2015
Actual Study Completion Date : May 18, 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DX-2930, Cohort 1
Participants will receive 30 milligram (mg) dose of DX-2930 subcutaneous (SC) injection once and followed by the second dose after 2 week into the upper arm.
Drug: DX-2930
Participants will receive SC injection of DX-2930 (a recombinant, Chinese hamster ovary [CHO] cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody) once and followed by the second dose after 2 week into the upper arm.

Experimental: DX-2930, Cohort 2
Participants will receive 100 mg dose of DX-2930 SC injection once and followed by the second dose after 2 week into the upper arm.
Drug: DX-2930
Participants will receive SC injection of DX-2930 (a recombinant, Chinese hamster ovary [CHO] cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody) once and followed by the second dose after 2 week into the upper arm.

Experimental: DX-2930, Cohort 3
Participants will receive 300 mg dose of DX-2930 SC injection once and followed by the second dose after 2 week into the upper arm.
Drug: DX-2930
Participants will receive SC injection of DX-2930 (a recombinant, Chinese hamster ovary [CHO] cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody) once and followed by the second dose after 2 week into the upper arm.

Experimental: DX-2930, Cohort 4
Participants will receive 400 mg dose of DX-2930 subcutaneous (SC) injection once and followed by the second dose after 2 week into the upper arm.
Drug: DX-2930
Participants will receive SC injection of DX-2930 (a recombinant, Chinese hamster ovary [CHO] cell expressed, fully human immunoglobulin IgG1, kappa light chain, monoclonal antibody) once and followed by the second dose after 2 week into the upper arm.

Placebo Comparator: Placebo
Participants will receive placebo matched to 30, 100, 300 and 400 mg dose of DX-2930 SC injection once and followed by the second dose after 2 week into the upper arm.
Drug: Placebo
Participants will receive matching placebo subcutaneously.




Primary Outcome Measures :
  1. Number of Participants With Serious Adverse Events (SAE) and Treatment-Emergent Adverse Events (TEAE) [ Time Frame: From Day 1 up to final follow-up (Day 123) ]
    A SAE was any adverse experience occurring at any dose that resulted in any of the following outcomes: Death, Life-threatening experience, required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant disability or incapacity. Was a congenital anomaly or birth defect. Was considered to be an important medical event. 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.


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) [ Time Frame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120 ]
    Pharmacokinetic (PK) parameter Cmax data were reported.

  2. Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120 ]
    PK parameter Tmax data were reported.

  3. Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120 ]
    PK paramenter AUC data were reported.

  4. Apparent Clearance (CL/F) [ Time Frame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120 ]
    PK parameter CL/F data were reported.

  5. Apparent Volume of Distribution (Vd/F) [ Time Frame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120 ]
    PK parameter Vd/F data were reported.

  6. Terminal Elimination Half-Life (t1/2) [ Time Frame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120 ]
    PK parameter t(1/2) data were reported.


Other Outcome Measures:
  1. HAE Attack Rate Per Week From Day 8 to Day 50 [ Time Frame: Day 8 to Day 50 ]
    Analysis of this outcome measure was based on participants 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 pre-specified assessment period (Days 8 to 50; predicted to correspond to a period of notable drug exposure). Baseline HAE attack rate per week was a covariate, treatment group is a fixed effect, and participant was a random effect in the GEE model with independence working correlation structure.

  2. HAE Attacks Per Week From Day 8 to Day 92 [ Time Frame: Day 8 to Day 92 ]
    This endpoint analysis was based on participants 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 (Day 8 to Day 92 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 participant is a random effect in the GEE model with independence working correlation structure.

  3. HAE Attacks Per Week From Day 8 to Day 64 [ Time Frame: Day 8 to Day 64 ]
    This endpoint analysis was based on participants 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 (Day 8 to Day 64 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 participant is a random effect in the GEE model with independence working correlation structure.

  4. HAE Attack Rate Per Week From Day 1 to Day 50 [ Time Frame: Day 1 to Day 50 ]
    This endpoint analysis was based on participants 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 (Day 1 to Day 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 participant is a random effect in the GEE model with independence working correlation structure.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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 participant
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02093923


Locations
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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
Saint 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
Investigators
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Study Director: Study Director Takeda
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02093923    
Other Study ID Numbers: DX-2930-02
First Posted: March 21, 2014    Key Record Dates
Results First Posted: August 1, 2016
Last Update Posted: May 27, 2021
Last Verified: May 2021
Keywords provided by Takeda ( Shire ):
HAE
Additional relevant MeSH terms:
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Angioedema
Angioedemas, Hereditary
Vascular Diseases
Cardiovascular Diseases
Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hereditary Complement Deficiency Diseases
Primary Immunodeficiency Diseases
Genetic Diseases, Inborn
Immunologic Deficiency Syndromes