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

Sponsor
Alector Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT03636204
Collaborator
(none)
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Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
  • Biological: AL001
  • Other: Placebo
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
64 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation
Actual Study Start Date :
Sep 14, 2018
Actual Primary Completion Date :
Dec 31, 2019
Actual Study Completion Date :
Dec 31, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: AL001

Up to six single ascending doses of AL001

Biological: AL001
Active dose 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

Other: Placebo
Saline solution administered as a single infusion as palcebo.

Outcome Measures

Primary Outcome Measures

  1. 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

  1. Pharmacokinetics (PK) of AL001 [85 days]

    Serum and cerebrospinal fluid (CSF) concentration of AL001 at specified time points

  2. Maximum plasma concentration (Cmax) for AL001 [85 days]

    Evaluate Cmax for serum and CSF concentration of AL001 at specified time points

  3. Area under the curve concentration (AUC) for AL001 [85 days]

    Evaluate AUC for serum and CSF concentration of AL001 at specified time points

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama Birmingham Alabama United States 35294
2 UCSF San Francisco California United States 94158
3 Study site Orlando Florida United States 32806
4 Mayo Clinic Rochester Minnesota United States 55905
5 University of Pennsylvania Philadelphia Pennsylvania United States 19104
6 Lawson Health Research Institute, St. Joseph's London Ontario Canada
7 Sunnybrook Health Sciences Centre Toronto Canada
8 University College London London United Kingdom WC1N 3BG

Sponsors and Collaborators

  • Alector Inc.

Investigators

  • Principal Investigator: George Stoica, Bioclinica Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Alector Inc.
ClinicalTrials.gov Identifier:
NCT03636204
Other Study ID Numbers:
  • AL001-1
First Posted:
Aug 17, 2018
Last Update Posted:
Jul 27, 2020
Last Verified:
Jul 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 27, 2020