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

Phase 1

Completed

• Conditions: Healthy; Frontotemporal Dementia
• Interventions: Other: Placebo; Biological: AL001

• Registration Number: NCT03636204
• Lead Sponsor: Alector Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-07-12
• Study First Submitted QC: 2018-08-15
• Study First Posted: 2018-08-17
• Study Start: 2018-09-14
• Primary Completion: 2019-12-31
• Study Completion: 2019-12-31
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-23
• Last Update Posted: 2020-07-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Saline Solution	Placebo	Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects
AL001	AL001	Up to six single ascending doses of AL001

Primary Outcome Measures

Name	Time	Method
Evaluation of safety and tolerability of AL001 measured by number of subjects with adverse events and Dose Limiting Adverse Event (DLAEs)	85 days	Incidence of adverse events and dose limiting Adverse Events during the DLAE observation period and/or study treatment periods.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK) of AL001	85 days	Serum and cerebrospinal fluid (CSF) concentration of AL001 at specified time points
Maximum plasma concentration (Cmax) for AL001	85 days	Evaluate Cmax for serum and CSF concentration of AL001 at specified time points
Area under the curve concentration (AUC) for AL001	85 days	Evaluate AUC for serum and CSF concentration of AL001 at specified time points

Trial Locations

Locations (8)

Study site; 🇺🇸 Orlando, Florida, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Canada

Lawson Health Research Institute, St. Joseph's; 🇨🇦 London, Ontario, Canada

University College London; 🇬🇧 London, United Kingdom

UCSF; 🇺🇸 San Francisco, California, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States