Clinical trial NCT02093923: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hereditary Angioedema (HAE)
Keywords: HAE
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-03-21
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants With Serious Adverse Events (SAE) and Treatment-Emergent Adverse Events (TEAE)
timeFrame: From Day 1 up to final follow-up (Day 123)
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
measure: Area Under the Plasma Concentration-Time Curve (AUC)
timeFrame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
measure: Apparent Clearance (CL/F)
timeFrame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
measure: Apparent Volume of Distribution (Vd/F)
timeFrame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
measure: Terminal Elimination Half-Life (t1/2)
timeFrame: Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Other outcomes:
measure: HAE Attack Rate Per Week From Day 8 to Day 50
timeFrame: Day 8 to Day 50
measure: HAE Attacks Per Week From Day 8 to Day 92
timeFrame: Day 8 to Day 92
measure: HAE Attacks Per Week From Day 8 to Day 64
timeFrame: Day 8 to Day 64
measure: HAE Attack Rate Per Week From Day 1 to Day 50
timeFrame: Day 1 to Day 50
Locations:
city: San Diego
country: United States
facility: UC San Diego Health System - La Jolla
state: California
city: Walnut Creek
country: United States
facility: Allergy & Asthma Clinical Research
state: California
city: Tampa
country: United States
facility: University of South Florida Asthma, Allergy or Immunology Clinical Research Unit
state: Florida
city: Chevy Chase
country: United States
facility: Institute for Asthma & Allergy, PC
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Allergy Associates
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Mineola
country: United States
facility: Winthrop-University Hospital, Clinical Trials Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
state: New York
city: Cincinnati
country: United States
facility: UC Physicians Company
state: Ohio
city: Lake Oswego
country: United States
facility: Baker Allergy, Asthma and Dermatology Research Center
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: AARA Research Center
state: Texas
city: Milano
country: Italy
facility: Ospedale L. Sacco
state: MI
city: Amman
country: Jordan
facility: Jordan University Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
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.