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

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

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.

Study Overview

• Status: Completed
• Conditions: Hereditary Angioedema (HAE)
• Intervention / Treatment: Drug: DX-2930; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • MI
    • Milano, MI, Italy, 20157
      • Ospedale L. Sacco
• Jordan
  • Amman, Jordan, 11942
    • Jordan University Hospital
• United States
  • California
    • San Diego, California, United States, 92122
      • UC San Diego Health System - La Jolla
    • Walnut Creek, California, United States, 94598
      • Allergy & Asthma Clinical Research
  • Florida
    • Tampa, Florida, United States, 33613
      • University of South Florida Asthma, Allergy or Immunology Clinical Research Unit
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Institute for Asthma & Allergy, PC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Allergy Associates
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop-University Hospital, Clinical Trials Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai - The Mount Sinai Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Physicians Company
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • Baker Allergy, Asthma and Dermatology Research Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • AARA Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2014
• Primary Completion (Actual): May 18, 2015
• Study Completion (Actual): May 18, 2015

Study Registration Dates

• First Submitted: March 17, 2014
• First Submitted That Met QC Criteria: March 19, 2014
• First Posted (Estimate): March 21, 2014

Study Record Updates

• Last Update Posted (Actual): May 27, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: HAE
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Vascular; Hypersensitivity; Urticaria; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Angioedema; Angioedemas, Hereditary
• Other Study ID Numbers: DX-2930-02