Single and Multiple Ascending Dose Study of ADX-914 in Healthy Adult Volunteers

Study Overview
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Brief Summary
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A two (2) part study to evaluate the safety, tolerability and PK of ADX-914

Detailed Description
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Part 1 - SAD: It is expected that there will be up to 6 cohorts of 8 participants per cohort. In each cohort, participants will be randomly assigned in a 3:1 ratio to receive either ADX-914 or matching placebo. It is planned that for each cohort in Part 1 a staggered 'sentinel' dose design will be used. Part 2 - MAD It is expected that there will be up to 3 cohorts of 8 participants per cohort. In each cohort, participants will be randomly assigned in a 3:1 ratio to receive either ADX-914 or matching placebo. Doses will occur every 2 weeks, for a total of 4 doses.

Official Title
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A Double-Blind, Phase 1, Single and Multiple Ascending Dose Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of ADX-914 in Healthy Volunteers

Conditions
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Safety Issues

Intervention / Treatment
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* Drug: ADX-914
* Drug: Placebo
* Drug: ADX-914
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy as determined by the Investigator, based on a medical evaluation including medical history, physical examination, laboratory tests and ECG recording Men and women age 18-50 Exclusion Criteria: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels greater than 1.5 x the upper limit of normal (ULN) at Screening or Day -1. QT-interval measurements corrected according to the Fridericia rule (QTcF >450 msec) during controlled rest at Screening or family history of long QT syndrome. Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any abnormalities in the 12-lead ECG that, in the judgment of the Investigator, may interfere with the interpretation of QTc-interval changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy. A clinically significant vital signs abnormality, as judged by the Investigator, at Screening, or Day -1. This includes, but is not limited to, the following, in the supine position: (a) systolic blood pressure <90 or >140 mmHg, (b) diastolic blood pressure <40 or >90 mmHg, or (c) heart rate <40 or >100 beats per minute.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: Cohort 1:1 - 1:6 ADX-914<br>ADX-914 single SC dose | Drug: ADX-914<br>* Single dose from 0.1mg/kg to TBD<br>|
| Placebo Comparator: Placebo Comparator: Cohort 1:1 - 1:6 placebo<br>Placebo single SC dose | Drug: Placebo<br>* Matching single dose placebo<br>|
| Experimental: Experimental: Cohort 2:1- 2:3<br>ADX-914 multiple SC dose once every 2 weeks for 6 weeks | Drug: ADX-914<br>* Multiple dose from TBD to TBD<br>|
| Placebo Comparator: Placebo Comparator: Cohort 2:1- 2:3<br>Placebo multiple SC dose once every 2 weeks for 6 weeks | Drug: Placebo<br>* Matching multiple dose placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events | Listing and summary of AE incidence | Screening to end of study, up to 18 weeks | 
| Number of subjects with Physical exam findings | Listing of clinically significant changes in PE findings | Screening to end of study, up to 18 weeks | 
| Number of subjects with Clinical safety lab changes | Listing and change from baseline to end of study | Screening to end of study, up to 18 weeks | 
| Number of subjects with Systolic blood pressure changes | Listing and change from baseline to end of study | Screening to end of study, up to 18 weeks | 
| Number of subjects with Heart rate changes | Listing and change from baseline to end of study | Screening to end of study, up to 18 weeks | 
| Number of subjects with 12 Lead ECG changes | Change in 12-lead ECG parameters from baseline to end of study | Screening to end of study, up to 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration, Cmax | Of ADX-914 | Predose to Day 91 (SAD) and Day 127 (MAD) | 
| Time to reach maximum observed plasma concentration, Tmax | Of ADX-914 | Predose to Day 91 (SAD) and Day 127 (MAD) | 
| Area Under the plasma concentration time curve, AUC | Of ADX-914 | Predose to Day 91 (SAD) and Day 127 (MAD) |