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

Overview

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

Full Title of Study: “A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: December 31, 2019

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.

Interventions

• Biological: AL001
  • Active dose of AL001
• Other: Placebo
  • Saline solution administered as a single infusion as palcebo.

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

• Lead Sponsor
  • Alector Inc.
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • George Stoica, Principal Investigator, Bioclinica Research