A Phase 1 First in Human Study to Assess Safety and Tolerability of AL101

Study Overview
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Brief Summary
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A first in human phase 1 study in healthy volunteers to assess AL101 safety, tolerability, bioavailability, pharmacokinetics, and pharmacodynamics

Detailed Description
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This is a first-in-human Phase 1 study designed to investigate the safety, tolerability, PK, PD and Bioavailability of intravenously and sub-cutaneously administered AL101 in Healthy Volunteers.

Official Title
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A Phase 1 Study in Healthy Volunteers to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Bioavailability of IV and SC AL101

Conditions
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Healthy

Intervention / Treatment
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* Biological: AL101
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI 18.0-35.0 kg/m2 45-120 kg, inclusive At screening, females must be non-pregnant and non-lactating, or of nonchildbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1-year postmenopausal (amenorrhoea duration of 12 consecutive months); nonpregnancy will be confirmed for all females by a pregnancy test conducted at screening, (each) admission, and at follow-up. Female participants of child-bearing potential must agree to use adequate contraception from screening until 90 days after the follow-up visit. In good physical health on the basis of no clinically significant findings from medical history, physical examination (PE), laboratory tests, 12 lead ECG, and vital signs, as judged by the Investigator. Willingness and able to comply with the study protocol, in the investigator's judgement. Exclusion Criteria: Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins. Positive drug or alcohol at screening and prior to first dose History of alcohol abuse or substance abuse

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AL101 IV<br>Up to four single ascending doses (SAD IV cohorts) Multiple doses of AL101 administered IV (MD IV cohort) | Biological: AL101<br>* Active dose of AL101<br>|
| Placebo Comparator: Saline Solution<br>Saline solution will be administered with the following: Single IV infusion for four single ascending doses (SAD IV cohorts) in a ratio of 8 active and 3 placebo subjects Multiple IV infusions for the MD IV cohort in a ratio of 8 active and 2 placebo subjects | Other: Placebo<br>* Saline solution administered as a single and multiple infusion as placebo.<br>|
| Experimental: AL101 SC<br>Single fixed dose levels of AL101 administered SC Multiple fixed dose of AL101 administered SC | Biological: AL101<br>* Active dose of AL101<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety and tolerability of AL101 measured by number of subjects with adverse events and Dose Limiting Adverse Event (DLAEs) | Incidence of adverse events and dose limiting Adverse Events during the DLAE observation period and/or study treatment periods. | either 57, 113, or 141 days, depending on the cohort | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of AL101 | Serum and CSF concentration of AL101 at specified time points | either 57, 113, or 141 days, depending on the cohort | 
| Maximum plasma concentration (Cmax) for AL101 | Evaluate Cmax for serum and CSF concentration of AL101 at specified time points | either 57, 113, or 141 days, depending on the cohort | 
| Area under the curve concentration (AUC) for AL101 | Evaluate AUC for serum and CSF concentration of AL101 at specified time points | either 57, 113, or 141 days, depending on the cohort |