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

• 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: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

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.

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

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

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

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

• Study Director: Study Director; Takeda

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT02093923
• Other Study ID Numbers: DX-2930-02
• First Posted: March 21, 2014
• 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:

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