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

Hereditary Angioedema (HAE) Clinical Trial

Official title:

A Phase 1b, Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02093923
• Other study ID #: DX-2930-02
• Status: Completed
• Phase: Phase 1
• Start date: May 14, 2014
• Est. completion date: May 18, 2015

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: May 18, 2015
• Est. primary completion date: May 18, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema (HAE)

Intervention

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
Participants will receive matching placebo subcutaneously.

Locations

Country	Name	City	State
Italy	Ospedale L. Sacco	Milano	MI
Jordan	Jordan University Hospital	Amman
United States	Massachusetts General Hospital Allergy Associates	Boston	Massachusetts
United States	Institute for Asthma & Allergy, PC	Chevy Chase	Maryland
United States	UC Physicians Company	Cincinnati	Ohio
United States	AARA Research Center	Dallas	Texas
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	Baker Allergy, Asthma and Dermatology Research Center	Lake Oswego	Oregon
United States	Winthrop-University Hospital, Clinical Trials Center	Mineola	New York
United States	Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UC San Diego Health System - La Jolla	San Diego	California
United States	University of South Florida Asthma, Allergy or Immunology Clinical Research Unit	Tampa	Florida
United States	Allergy & Asthma Clinical Research	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Italy,  Jordan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	HAE Attack Rate Per Week From 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.	Day 8 to Day 50
Other	HAE Attacks Per Week From 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.	Day 8 to Day 92
Other	HAE Attacks Per Week From 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.	Day 8 to Day 64
Other	HAE Attack Rate Per Week From 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.	Day 1 to Day 50
Primary	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.	From Day 1 up to final follow-up (Day 123)
Secondary	Maximum Plasma Concentration (Cmax)	Pharmacokinetic (PK) parameter Cmax data were reported.	Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Secondary	Time to Maximum Plasma Concentration (Tmax)	PK parameter Tmax data were reported.	Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Secondary	Area Under the Plasma Concentration-Time Curve (AUC)	PK paramenter AUC data were reported.	Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Secondary	Apparent Clearance (CL/F)	PK parameter CL/F data were reported.	Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Secondary	Apparent Volume of Distribution (Vd/F)	PK parameter Vd/F data were reported.	Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120
Secondary	Terminal Elimination Half-Life (t1/2)	PK parameter t(1/2) data were reported.	Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120