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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hereditary Angioedema (HAE)

Intervention / Treatment
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* Drug: DX-2930
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DX-2930, Cohort 1<br>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<br>* 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.<br>|
| Experimental: DX-2930, Cohort 2<br>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<br>* 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.<br>|
| Experimental: DX-2930, Cohort 3<br>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<br>* 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.<br>|
| Experimental: DX-2930, Cohort 4<br>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<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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<br>* Participants will receive matching placebo subcutaneously.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAE