Safety and Pharmacokinetics Study in Healthy Japanese Volunteers

Study Overview
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Brief Summary
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The study consists of Part A, a randomized double-blind, single-ascending-dose study, and Part B, a randomized, double-blind, semi-sequential, escalating multiple-dose study, in healthy Japanese volunteers.

Detailed Description
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Part A includes the following two dose regimen groups: 25 mg dose regimen group: ABX464 25 mg or placebo 50 mg dose regimen group: ABX464 50 mg or placebo In each dose regimen group, 12 subjects will be randomly assigned, according to a 3:1 ratio, to receive either ABX464 (9 subjects) or its matching placebo (3 subjects). Part B includes the following two dose regimen groups: 25 mg dose regimen group: ABX464 25 mg or placebo for 28 days 50 mg dose regimen group: ABX464 50 mg or placebo for 28 days In each dose regimen group, 12 subjects will be randomly assigned, according to a 3:1 ratio, to receive either ABX464 (9 subjects) or its matching placebo (3 subjects).

Official Title
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A Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics After Single and Multiple Doses of ABX464 Capsules in Healthy Japanese Volunteers.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ABX464
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male Japanese volunteers. 20 to 45 years old. Considered by the Investigator, as healthy based on history, physical examination, and complete laboratory evaluation (laboratory parameters should be within normal ranges of the study center's laboratory or considered not clinically significant by the Investigator). Vital signs (supine blood pressure, resting pulse rate, body temperature) should be within normal ranges and no deviation from standard 12-lead electrocardiogram (ECG) should be observed at screening. Body mass index (BMI) should be between 18 (inclusive) and 27 kg/m² (inclusive). Non-smokers at enrolment. Subjects must understand, sign and date the written voluntary Informed Consent Form at the visit prior to any protocol-specific procedures. Able and willing to comply with study visits and procedures as per protocol. Males receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 6 months after the last dose of study drug. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal ligation, and vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the subject. In each case of delayed menstrual period (over 1 month between menstruations) in a female partner of a male subject, confirmation of absence of pregnancy of the partner is required. Male subjects must not be planning pregnancy, should use a condom and must not donate sperm during the study and for 6 months after the last dose of study drug. Exclusion Criteria: Acute disease state (e.g., nausea, vomiting, diarrhea, or fever within a week) or chronic infectious disease (positive results for hepatitis B surface antigen [HBsAg], hepatitis C virus antibody, human immunodeficiency virus antigen/antibody, tuberculosis determined by QuantiFERON-TB Gold Plus test). Subjects who have positive hepatitis B core antibody [HBcAb] can be enrolled but must have an undetectable hepatitis B virus [HBV] viral load (HBV DNA test). Positive results for SARS-CoV-2 antigen determined by polymerase chain reaction method. History of recent grade 3 or 4 opportunistic infection or underlying conditions that may predispose them to grade 3 or grade 4 infection. History of cardiovascular, pulmonary, gastrointestinal, hepatic, pancreatic, renal, metabolic, hematological, neurological, psychiatric, or systemic disease that could jeopardize the safety of the subject or the validity of the study results. Illicit drug or alcohol abuse, or dependence within a year. Blood donation within 3 months prior to screening. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer. Use of any immunosuppressive drugs (except topical steroids) within 3 months prior to first dose. Any history of hypersensitivity to drugs. Any condition, which in the opinion of the Investigator, could compromise the subject's safety or adherence to the study protocol

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part A: single-ascending-dose Part B: escalating multiple-dose
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 25 mg single dose<br>Subject will receive a single oral dose of ABX464 25 mg or its matching placebo | Drug: ABX464<br>* Drug: ABX464 ABX464 is a new anti-inflammatory drug<br>Drug: Placebo<br>* Drug: Matching Placebo placebo matching with ABX464<br>|
| Experimental: 50 mg single dose<br>Subject will receive a single oral dose of ABX464 50 mg or its matching placebo | Drug: ABX464<br>* Drug: ABX464 ABX464 is a new anti-inflammatory drug<br>Drug: Placebo<br>* Drug: Matching Placebo placebo matching with ABX464<br>|
| Experimental: 25 mg multiple dose<br>Subject will receive a daily oral dose of ABX464 25 mg or its matching placebo for 28 days | Drug: ABX464<br>* Drug: ABX464 ABX464 is a new anti-inflammatory drug<br>Drug: Placebo<br>* Drug: Matching Placebo placebo matching with ABX464<br>|
| Experimental: 50 mg mulptiple dose<br>Subject will receive a daily oral dose of ABX464 50 mg or its matching placebo for 28 days | Drug: ABX464<br>* Drug: ABX464 ABX464 is a new anti-inflammatory drug<br>Drug: Placebo<br>* Drug: Matching Placebo placebo matching with ABX464<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) and SAEs | number of incidences of all adverse events (AEs) (causally related and non-related) and SAEs, will be described further categorized by severity | 6 weeks | 
| incidence of treatment-emergent serious adverse events | number of incidences of treatment-emergent serious adverse events will be described | 6 weeks | 
| incidence of treatment-emergent adverse events of special interest (AESIs). | number of incidences of treatment-emergent adverse events of special interest (AESIs) will be described. | 6 weeks | 
| incidence of clinically significant laboratory abnormalities | number of incidences of clinically significant laboratory abnormalities will be described | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration [Cmax] | Cmax of ABX464 will be derived from the plasma concentrations | 42 days | 
| Area under the plasma concentration versus time curve (AUC) | AUC of ABX464 will be derived from the plasma concentrations | 42 days | 
| Time to reach the maximum plasma concentration (tmax) | Tmax of ABX464 will be derived from the plasma concentrations | 42 days | 
| miR124 level | concentration of miR124 expression will be measured in blood | 42 days |