A Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AL001 in FTD.

• Register: EUCTR
• Last refreshed on: 3 December 2024
• Main ID: EUCTR2019-004066-18-IT
• Date of registration: 15/06/2021
• Prospective Registration: No
• Primary sponsor: Alector Inc.
• Public title: A Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of AL001 in FTD.
• Scientific title: A Phase 3, Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of AL001 in Individuals at Risk for or With Frontotemporal Dementia Due to Heterozygous Mutations in the Progranulin Gene. - NA
• Date of first enrolment: 18/05/2020
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-004066-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, France, Germany, Italy, Netherlands, Portugal, Spain, Sweden, Switzerland, United Kingdom, United States

Contacts

• Name: Kristina Vlaovic
• Affiliation: Alector Inc.

• Name: Kristina Vlaovic
• Affiliation: Alector Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• Known progranulin genetic mutation causing FTD.
• CDR plus NACC-FTLD score 0-2.
• If symptomatic, one of the criteria for the diagnosis of probable behavioral variant FTD or FTD-semantic subtype or FTD-Progressive Nonfluent Aphasia.
• Study partner who consents to study participation and who cares for/visits the patient daily for at least 5 hours per week.
• Written informed consent must be obtained and documented (from the patient or, where jurisdictions allow it, from their legal decision maker).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 144
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion criteria:
Dementia due to a condition other than FTD including, but not limited to, Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies,
Huntington disease, or vascular dementia.
Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
Current uncontrolled hypertension, diabetes mellitus or thyroid disease.
Clinically significant heart disease, liver disease or kidney disease.
History or evidence of clinically significant brain disease other than FTD.
Females who are pregnant or breastfeeding, or planning to conceive within the study period.
Any experimental vaccine or gene therapy.
History of cancer except:
If considered to be cured
If not being actively treated with anti-cancer therapy or radiotherapy and, in the opinion of the investigator, not likely to require treatment in the ensuing 3 years
Is considered to have low probability of recurrence
For prostate cancer, no significant progression over the previous 2 years
Current use of anticoagulant medications (e.g., coumadin, heparinoids, apixaban).
Residence in a skilled nursing facility, convalescent home, or long term care facility at screening; or requires continuous nursing care.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Frontotemporal Dementia.
MedDRA version: 21.1 Level: PT Classification code 10068968 Term: Frontotemporal dementia System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: AL001
Product Code: [AL001]
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: AL001
CAS Number: 2376132-27-1
Current Sponsor code: AL001
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of AL001 compared with placebo in carriers of progranulin gene (GRN) mutations causative of frontotemporal dementia (FTD) as measured by the Clinical Dementia Rating Dementia Staging Instrument PLUS National Alzheimer's Disease Coordinating Center frontotemporal lobar degeneration Behavior & Language Domains Sum
of Boxes (CDR® plus NACC FTLD-SB).

Primary end point(s): •The CDR® plus NACC FTLD-SB

Secondary Objective: The secondary objectives of this study are to evaluate the clinical effects, safety, and tolerability of AL001 compared with placebo in carriers of GRN mutations causative of FTD as measured by:
Secondary Objective: Clinical outcome assessments (COAs)
Secondary Pharmacodynamic (PD) Objective: Disease pathology biomarkers
Secondary Safety Objective: Safety assessments and antidrug antibodies (ADAs)

Timepoint(s) of evaluation of this end point: Baseline and weeks 16, 32 and 48 for symptomatic patients and baseline and weeks 16,32, 48, 64, 80 and 96 for pre symptomatic patients.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Secondary endpoints: every 16 weeks.
PD endpoints: MRI every 24 weeks PGRN and NfL measurements every 8 weeks and safety assessments every 4 weeks.

Secondary end point(s): •Clinical Global Impression-Severity (CGI S)
•Clinical Global Impression-Improvement (CGI I)
•The changes from baseline in the scores of the following COAs:
o Frontotemporal Dementia Rating Scale (FRS)
o Repeatable Battery for the Assessment of Neuropsychological Status
(RBANS)
Secondary PD Endpoints:
•The changes from baseline in the following:
o Structural volumetric magnetic resonance imaging (MRI) whole and
regional brain volume
o Progranulin protein (PGRN) concentrations in plasma and optional cerebrospinal fluid (CSF)
o Neurofilament-light chain (NfL) concentrations in serum and optional CSF
Secondary Safety Endpoints:
•Incidence, nature, and severity of adverse events and serious adverse events
•Physical examination abnormalities
•Neurological examination abnormalities
•Changes in vital signs from baseline over time
•Changes in electrocardiograms from baseline over time
•MRI abnormalities
•Changes in clinical laboratory tests from baseline over time
•Sheehan-Suicidality Tracking Scale (Sheehan STS)
•Incidence of ADAs to AL001

Secondary ID(s)

2019-004066-18-DE

NCT04374136

135892

AL001-3

Source(s) of Monetary Support

Alector Inc.

Ethics review

Status: Approved
Approval date: 31/03/2020
Contact: