Back to resultsA First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation
Primary Purpose
Healthy, Frontotemporal Dementia
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AL001
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Healthy
Eligibility Criteria
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
Sites / Locations
- University of Alabama
- UCSF
- Study site
- Mayo Clinic
- University of Pennsylvania
- Lawson Health Research Institute, St. Joseph's
- Sunnybrook Health Sciences Centre
- University College London
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AL001
Saline Solution
Arm Description
Up to six single ascending doses of AL001
Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Pharmacokinetics (PK) of AL001
Serum and cerebrospinal fluid (CSF) concentration of AL001 at specified time points
Maximum plasma concentration (Cmax) for AL001
Evaluate Cmax for serum and CSF concentration of AL001 at specified time points
Area under the curve concentration (AUC) for AL001
Evaluate AUC for serum and CSF concentration of AL001 at specified time points
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03636204
Brief Title
A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation
Official Title
A First in Human Phase 1 Study in Healthy Volunteers and in Participants With Frontotemporal Dementia (FTD) With Granulin Mutation
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
September 14, 2018 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alector Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. 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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Frontotemporal Dementia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AL001
Arm Type
Experimental
Arm Description
Up to six single ascending doses of AL001
Arm Title
Saline Solution
Arm Type
Placebo Comparator
Arm Description
Saline solution will be administered as a single infusion for each cohort in a ratio of 6 active and 2 placebo subjects
Intervention Type
Biological
Intervention Name(s)
AL001
Intervention Description
Active dose of AL001
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Saline solution administered as a single infusion as palcebo.
Primary Outcome Measure Information:
Title
Evaluation of safety and tolerability of AL001 measured by number of subjects with adverse events and Dose Limiting Adverse Event (DLAEs)
Description
Incidence of adverse events and dose limiting Adverse Events during the DLAE observation period and/or study treatment periods.
Time Frame
85 days
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of AL001
Description
Serum and cerebrospinal fluid (CSF) concentration of AL001 at specified time points
Time Frame
85 days
Title
Maximum plasma concentration (Cmax) for AL001
Description
Evaluate Cmax for serum and CSF concentration of AL001 at specified time points
Time Frame
85 days
Title
Area under the curve concentration (AUC) for AL001
Description
Evaluate AUC for serum and CSF concentration of AL001 at specified time points
Time Frame
85 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
George Stoica
Organizational Affiliation
Bioclinica Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Study site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Lawson Health Research Institute, St. Joseph's
City
London
State/Province
Ontario
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
Country
Canada
Facility Name
University College London
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A First in Human Study in Healthy Volunteers and in Participants With Frontotemporal Dementia With Granulin (GRN) Mutation
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