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)

Enrollment

Locations

Arms

15.5

Actual Duration (Months)

Patients Per Site

0.5

Patients Per Site Per Month

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
Healthy Frontotemporal Dementia	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.

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

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

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

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:

Additional relevant MeSH terms:

Dementia

Frontotemporal Dementia

Aphasia, Primary Progressive

Pick Disease of the Brain

Study Results

No Results Posted as of Jul 27, 2020