A Study of AST-008 in Healthy Subjects

Study Overview
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Brief Summary
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AST-008 will be dosed subcutaneously to healthy volunteers in a combined SAD/MAD study to evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics.

Official Title
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A Randomized, Combined SAD/MAD Phase 1 Study of the Safety, Pharmacokinetics and Pharmacodynamics of AST 008 in Healthy Subjects

Conditions
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Healthy Volunteer Study

Intervention / Treatment
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* Drug: AST-008


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Healthy male or female subjects aged ≥18 and ≤40 years of age at the time of first dosing. Subjects must have a body mass index (BMI) between 18.0-25.0 kg/m² inclusive. Satisfactory medical assessment with no clinically significant or relevant abnormalities as determined by medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluation (haematology, biochemistry, coagulation, and urinalysis) that is reasonably likely to interfere with the subject's participation in or ability to complete the study as assessed by the Investigator. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH Good Clinical Practice (GCP) Guideline E6 (1996) and applicable regulations, before completing any study-related procedures. An understanding, ability, and willingness to fully comply with study procedures and restrictions. Main Exclusion Criteria: Current or recurrent disease (e.g., cardiovascular, haematological, neurological, endocrine, renal, liver, GI or other conditions) that could affect the action, absorption, or disposition of AST-008, or could affect clinical assessments or clinical laboratory evaluations. Any history of cancer. Any history (including significant and confirmed family history) of autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, autoimmune hepatitis, or thrombocytopenia. Has had an acute illness within two weeks prior to screening. Current or relevant history of physical or psychiatric illness that may require treatment or make the subject unlikely to fully comply with the requirements of the study or complete the study, or any condition that presents undue risk from the investigational product or study procedures. Any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study may influence the result of the study, or the subject's ability to participate in the study. Female subjects who are pregnant or breastfeeding. Subjects with abnormal findings of inguinal, axillary, or cervical lymph nodes at screening or Day -1. A positive human immunodeficiency virus (HIV) antibody screen, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody screen. Titres above reference ranges (according to local laboratory) for autoimmune antibodies: rheumatoid factor (RF), anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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: Screening
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose<br> | Drug: AST-008<br>* AST-008 is a toll-like receptor 9 agonist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious related adverse events | To evaluate SAEs after a single subcutaneous dose of AST-008 | Up to 1 month after the last dose of AST-008 | 
| Adverse events | To evaluate adverse events after a single subcutaneous dose of AST-008 | Up to 1 month after the last dose of AST-008 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose finding | To recommend a dose and regimen for further development. | Up to 1 month after the last dose of AST-008 | 
| Maximum plasma concentration assessment | Measurement of the maximum observed plasma concentration (Cmax) after single doses of AST-008 | Up to 1 month after the last dose of AST-008 | 
| AUC assessment | Measurement of the area under the curve (AUC) after single doses of AST-008 | Up to 1 month after the last dose of AST-008 | 
| Pharmacodynamics | Measurement of type 1 cytokine concentrations as a function of time after single doses of AST-008 | Up to 1 month after the last dose of AST-008 | 
| Pharmacodynamics | Measurement of changes in absolute number and and fraction of a panel of lymphocyte markers as a function of time after single doses of AST-008 | Up to 1 month after the last dose of AST-008 | 
| QTc interval testing | To determine the effect of AST-008 on QTc interval | Up to 1 month after the last dose of AST-008 |