Back to resultsA Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Participants
Primary Purpose
Hereditary Angioedema (HAE)
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DX-2930
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hereditary Angioedema (HAE) focused on measuring HAE
Eligibility 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
Sites / Locations
- UC San Diego Health System - La Jolla
- Allergy & Asthma Clinical Research
- University of South Florida Asthma, Allergy or Immunology Clinical Research Unit
- Institute for Asthma & Allergy, PC
- Massachusetts General Hospital Allergy Associates
- Washington University School of Medicine
- Winthrop-University Hospital, Clinical Trials Center
- Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
- UC Physicians Company
- Baker Allergy, Asthma and Dermatology Research Center
- Penn State Hershey Medical Center
- AARA Research Center
- Ospedale L. Sacco
- Jordan University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
DX-2930, Cohort 1
DX-2930, Cohort 2
DX-2930, Cohort 3
DX-2930, Cohort 4
Placebo
Arm Description
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Number of Participants With Serious Adverse Events (SAE) and Treatment-Emergent Adverse Events (TEAE)
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
Maximum Plasma Concentration (Cmax)
Pharmacokinetic (PK) parameter Cmax data were reported.
Time to Maximum Plasma Concentration (Tmax)
PK parameter Tmax data were reported.
Area Under the Plasma Concentration-Time Curve (AUC)
PK paramenter AUC data were reported.
Apparent Clearance (CL/F)
PK parameter CL/F data were reported.
Apparent Volume of Distribution (Vd/F)
PK parameter Vd/F data were reported.
Terminal Elimination Half-Life (t1/2)
PK parameter t(1/2) data were reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02093923
Brief Title
A Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Participants
Official Title
A Phase 1b, Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
May 14, 2014 (Actual)
Primary Completion Date
May 18, 2015 (Actual)
Study Completion Date
May 18, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shire
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hereditary Angioedema (HAE)
Keywords
HAE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DX-2930, Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
DX-2930, Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
DX-2930, Cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
DX-2930, Cohort 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DX-2930
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive matching placebo subcutaneously.
Primary Outcome Measure Information:
Title
Number of Participants With Serious Adverse Events (SAE) and Treatment-Emergent Adverse Events (TEAE)
Description
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.
Time Frame
From Day 1 up to final follow-up (Day 123)
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax)
Description
Pharmacokinetic (PK) parameter Cmax data were reported.
Time Frame
Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Title
Time to Maximum Plasma Concentration (Tmax)
Description
PK parameter Tmax data were reported.
Time Frame
Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Title
Area Under the Plasma Concentration-Time Curve (AUC)
Description
PK paramenter AUC data were reported.
Time Frame
Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Title
Apparent Clearance (CL/F)
Description
PK parameter CL/F data were reported.
Time Frame
Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Title
Apparent Volume of Distribution (Vd/F)
Description
PK parameter Vd/F data were reported.
Time Frame
Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Title
Terminal Elimination Half-Life (t1/2)
Description
PK parameter t(1/2) data were reported.
Time Frame
Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Other Pre-specified Outcome Measures:
Title
HAE Attack Rate Per Week From Day 8 to Day 50
Description
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.
Time Frame
Day 8 to Day 50
Title
HAE Attacks Per Week From Day 8 to Day 92
Description
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.
Time Frame
Day 8 to Day 92
Title
HAE Attacks Per Week From Day 8 to Day 64
Description
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.
Time Frame
Day 8 to Day 64
Title
HAE Attack Rate Per Week From Day 1 to Day 50
Description
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.
Time Frame
Day 1 to Day 50
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
UC San Diego Health System - La Jolla
City
San Diego
State/Province
California
ZIP/Postal Code
92122
Country
United States
Facility Name
Allergy & Asthma Clinical Research
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Facility Name
University of South Florida Asthma, Allergy or Immunology Clinical Research Unit
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
Institute for Asthma & Allergy, PC
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Massachusetts General Hospital Allergy Associates
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Winthrop-University Hospital, Clinical Trials Center
City
Mineola
State/Province
New York
ZIP/Postal Code
11501
Country
United States
Facility Name
Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
UC Physicians Company
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Baker Allergy, Asthma and Dermatology Research Center
City
Lake Oswego
State/Province
Oregon
ZIP/Postal Code
97035
Country
United States
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Ospedale L. Sacco
City
Milano
State/Province
MI
ZIP/Postal Code
20157
Country
Italy
Facility Name
Jordan University Hospital
City
Amman
ZIP/Postal Code
11942
Country
Jordan
12. IPD Sharing Statement
Citations:
PubMed Identifier
28225674
Citation
Banerji A, Busse P, Shennak M, Lumry W, Davis-Lorton M, Wedner HJ, Jacobs J, Baker J, Bernstein JA, Lockey R, Li HH, Craig T, Cicardi M, Riedl M, Al-Ghazawi A, Soo C, Iarrobino R, Sexton DJ, TenHoor C, Kenniston JA, Faucette R, Still JG, Kushner H, Mensah R, Stevens C, Biedenkapp JC, Chyung Y, Adelman B. Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis. N Engl J Med. 2017 Feb 23;376(8):717-728. doi: 10.1056/NEJMoa1605767.
Results Reference
derived
Learn more about this trial
A Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Participants
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