Clinical trial NCT04374136: A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Frontotemporal Dementia
Lead sponsor: Alector Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2020-05-05
Enrollment: 110
Sex: ALL
Minimum age (years): 25
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A phase 3 double blind, placebo controlled study evaluating the efficacy and safety of AL001 in participants at risk for or with frontotemporal dementia due to heterozygous mutations in the progranulin gene.

Detailed description: This is a phase 3 double blind, placebo controlled study evaluating the efficacy and safety of AL001 administered intravenously in participants at risk for or with frontotemporal dementia due to heterozygous mutations in the progranulin gene. Study completion marks the end of the open label extension period following the 96-week blinded portion of the study.

Eligibility criteria: Inclusion Criteria:

* Persons with a progranulin gene mutation and at risk of developing FTD symptoms as evidenced by a biomarker, or persons with a progranulin gene mutation and diagnosed with FTD.
* If symptomatic, one or more of the criteria for the diagnosis of possible behavioral variant FTD, or a diagnosis of Primary Progressive Aphasia.
* Study partner who consents to study participation and who cares for/visits the participant daily for at least 5 hours per week.
* Written informed consent must be obtained and documented (from the participant or, where jurisdictions allow it, from their legal decision maker).

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 within the last 5 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.

Primary outcomes:
measure: Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB
timeFrame: Through study completion, on average up to 96 weeks
Secondary outcomes:
measure: Change in Clinical Global Impression-Severity (CGI-S) Score
timeFrame: Baseline to 96 weeks
measure: Change in Clinical Global Impression-Improvement (CGI-I) Score
timeFrame: Baseline to 96 weeks
measure: Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score
timeFrame: Baseline to 96 weeks
measure: Pharmacodynamic Biomarkers
timeFrame: Baseline to 96 weeks
measure: Evaluation of safety and tolerability of AL001: Incidence of adverse events
timeFrame: Baseline to 96 weeks
Other outcomes:
measure: Optional Open-Label Extension
timeFrame: 96 weeks
Locations:
city: Phoenix
country: United States
facility: Dignity Health
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Health Neuroscience Center
state: Indiana
city: Fairway
country: United States
facility: University of Kansas Alzheimer's Disease Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Rochester
country: United States
facility: Mayo Comprehensive Cancer Center - PPDS
state: Minnesota
city: New York
country: United States
facility: Irving Institute for Clinical and Translational Research
state: New York
city: Cincinnati
country: United States
facility: University Of Cincinnati Gardner Neuroscience institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Institute for Academic Medicine
state: Texas
city: Buenos Aires
country: Argentina
facility: Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia
city: Box Hill
country: Australia
facility: Box Hill Hospital
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams Brabant
city: London
country: Canada
facility: The University of Western Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute - University of Toronto
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Lille
country: France
facility: CHRU Lille
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpétrière
city: Köln
country: Germany
facility: Uniklinik Köln
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Athens
country: Greece
facility: Eginitio University General Hospital of Athens - 1st University Neurology Clinic
state: Attica
city: Alexandroupoli
country: Greece
facility: University General Hospital of Alexandroupolis - Department of Neurology
state: Evros
city: Baggiovara
country: Italy
facility: Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
city: Brescia
country: Italy
facility: IRCCS - Centro S. Giovanni di Dio Fatebenefratelli
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
city: Tricase
country: Italy
facility: PIA Fondazione Panico
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitário de Coimbra EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
city: Lisboa
country: Portugal
facility: Hospital CUF Descobertas
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto - Hospital de Santo António
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Donostia-san Sebastián
country: Spain
facility: Hospital Universitario de Donostia
city: Huddinge
country: Sweden
facility: Karolinska Universitetssjukhuset Huddinge - PPDS
city: Basel
country: Switzerland
facility: Felix Platter Spital
city: Istanbul
country: Turkey
facility: Istanbul University Medical Faculty
state: Fatih
city: London
country: United Kingdom
facility: University College London
Study officials:
name: TBD TBD
role: PRINCIPAL_INVESTIGATOR
References: