A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation

Study Overview
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Brief Summary
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A first in human phase 1 study in healthy volunteers and participants with Granulin (GRN) mutation causative of frontotemporal dementia (FTD) to assess AL001 safety, tolerability, 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 and PD of intravenously administered AL001 in Healthy Volunteers and FTD-GRN mutation carriers.

Official Title
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A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation

Conditions
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Healthy, Frontotemporal Dementia

Intervention / Treatment
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* Biological: AL001
* 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: 80 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: AL001<br>Up to six single ascending doses of AL001 | Biological: AL001<br>* Active dose of AL001<br>|
| Placebo Comparator: Saline Solution<br>Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects | Other: Placebo<br>* Saline solution administered as a single infusion as palcebo.<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 AL001 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. | 85 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK) of AL001 | Serum and cerebrospinal fluid (CSF) concentration of AL001 at specified time points | 85 days | 
| Maximum plasma concentration (Cmax) for AL001 | Evaluate Cmax for serum and CSF concentration of AL001 at specified time points | 85 days | 
| Area under the curve concentration (AUC) for AL001 | Evaluate AUC for serum and CSF concentration of AL001 at specified time points | 85 days |