A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
Primary Purpose
Frontotemporal Dementia
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AL001
Sponsored by
About this trial
This is an interventional treatment trial for Frontotemporal Dementia
Eligibility Criteria
Inclusion Criteria:
- At screening, female participants must be nonpregnant and nonlactating
- In good physical health on the basis of no clinically significant findings from medical history, physical examinations (PEs), laboratory tests, ECGs, and vital signs.
- Participant is a carrier of a loss of function progranulin gene (GRN) mutation or carrier of a hexanucleotide repeat expansion C9orf72 mutation
Exclusion Criteria:
- Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
- History of alcohol abuse or substance abuse
- Participant resides in a skilled nursing facility, convalescent home, or long term care facility
Sites / Locations
- UCSF
- Mayo Clinic
- University of Pennsylvania
- The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio
- Lawson Health Research Institute, St. Joseph's
- Sunnybrook Health Sciences Centre
- Technical University of Munich
- University of Ulm
- University of Brescia
- Brain Research Center - PPDS
- Erasmus University Medical Center
- University College London
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Granulin
C9orf72
Arm Description
IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]
IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]
Outcomes
Primary Outcome Measures
Part 1: Evaluation of safety and efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB
The CDR® plus NACC FTLD assessment is the CDR® plus the Frontotemporal Dementia Behavior and Language Domain scores from the NACC FTLD module. Data for this scale will be captured through completion of the standard CDR and a domain-specific container form labeled Frontotemporal Dementia Behavior and Language Domains (FTD-BLD). The necessary information to rate these domains is obtained through a semi-structured interview of the participant and a reliable informant or collateral source (e.g., a caregiver).
Secondary Outcome Measures
Maximum plasma concentration (Cmax) for AL001
Evaluate Cmax for concentration of AL001 at specified time points
Area under the curve concentration (AUC) for AL001
Evaluate AUC for concentration of AL001 at specified time points
Pharmacokinetics (PK) of AL001
Concentration of AL001 at specified time points
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03987295
Brief Title
A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
Official Title
A Phase 2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in Heterozygous Carriers of Granulin or C9orf72 Mutations Causative of Frontotemporal Dementia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 27, 2019 (Actual)
Primary Completion Date
January 28, 2026 (Anticipated)
Study Completion Date
June 2, 2026 (Anticipated)
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Phase 2 open label study evaluating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AL001 in participants with a Granulin mutation or C9orf72 mutation causative of frontotemporal dementia.
Detailed Description
This is a Phase 2, multicenter, open label study evaluating the safety, tolerability, PK and PD of AL001 administered intravenously in participants with a Granulin mutation or C9orf72 mutation causative of frontotemporal dementia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Frontotemporal Dementia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Granulin
Arm Type
Experimental
Arm Description
IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]
Arm Title
C9orf72
Arm Type
Experimental
Arm Description
IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]
Intervention Type
Drug
Intervention Name(s)
AL001
Intervention Description
60 mg/kg of AL001 every 4 weeks
Primary Outcome Measure Information:
Title
Part 1: Evaluation of safety and efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB
Description
The CDR® plus NACC FTLD assessment is the CDR® plus the Frontotemporal Dementia Behavior and Language Domain scores from the NACC FTLD module. Data for this scale will be captured through completion of the standard CDR and a domain-specific container form labeled Frontotemporal Dementia Behavior and Language Domains (FTD-BLD). The necessary information to rate these domains is obtained through a semi-structured interview of the participant and a reliable informant or collateral source (e.g., a caregiver).
Time Frame
96 weeks
Secondary Outcome Measure Information:
Title
Maximum plasma concentration (Cmax) for AL001
Description
Evaluate Cmax for concentration of AL001 at specified time points
Time Frame
96 weeks
Title
Area under the curve concentration (AUC) for AL001
Description
Evaluate AUC for concentration of AL001 at specified time points
Time Frame
96 weeks
Title
Pharmacokinetics (PK) of AL001
Description
Concentration of AL001 at specified time points
Time Frame
96 weeks
Other Pre-specified Outcome Measures:
Title
Part 2: Assess the long-term safety and tolerability of IV administration of AL001 as measured by the CDR® plus NACC FTLD-SB
Description
The primary objective of the OLE period of the study is to assess the long term safety and tolerability of AL001 in participants who have completed 96 weeks of treatment on Part 1 of the study
Time Frame
96 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
At screening, female participants must be nonpregnant and nonlactating
In good physical health on the basis of no clinically significant findings from medical history, physical examinations (PEs), laboratory tests, ECGs, and vital signs.
Participant is a carrier of a loss of function progranulin gene (GRN) mutation or carrier of a hexanucleotide repeat expansion C9orf72 mutation
Exclusion Criteria:
Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
History of alcohol abuse or substance abuse
Participant resides in a skilled nursing facility, convalescent home, or long term care facility
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Ljubenkov, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
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
The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Lawson Health Research Institute, St. Joseph's
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Technical University of Munich
City
Munchen
ZIP/Postal Code
81675
Country
Germany
Facility Name
University of Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
University of Brescia
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Brain Research Center - PPDS
City
Amsterdam
ZIP/Postal Code
1081GN
Country
Netherlands
Facility Name
Erasmus University Medical Center
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
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 Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
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