A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Frontotemporal Dementia
• Intervention / Treatment: Drug: AL001; Drug: Placebo; Drug: Open label - AL001

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.

• Study Type: Interventional
• Enrollment (Estimated): 110
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Study Lead; Phone Number: 650-826-2454; Email: clinicaltrials@alector.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, 2325
    • Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia
  • San Juan, Argentina, C1015ABR
    • INECO Castaño
  • Ciudad Autónoma De BuenosAires
    • Retiro, Ciudad Autónoma De BuenosAires, Argentina, C1058AAJ
      • CENydET S.R.L.
• Australia
  • Box Hill, Australia, 3128
    • Box Hill Hospital
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital
  • Woodville, Australia
    • The Queen Elizabeth Hospital
• Belgium
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven
• Canada
  • London, Canada
    • The University of Western Ontario
  • Toronto, Canada
    • Sunnybrook Research Institute - University of Toronto
• France
  • Bordeaux, France
    • CHU de Bordeaux
  • Lille, France
    • CHRU Lille
  • Paris, France
    • Groupe Hospitalier Pitié Salpétrière
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • CHU de Toulouse Hopital PURPAN
  • Seinne-Maritime
    • Rouen, Seinne-Maritime, France, 76000
      • Hopital Charles Nicolle - Hospital
• Germany
  • Köln, Germany, 50937
    • Uniklinik Koln
  • Ulm, Germany
    • Universitätsklinikum Ulm
• Greece
  • Attica
    • Athens, Attica, Greece, 115 28
      • Eginitio University General Hospital of Athens - 1st University Neurology Clinic
  • Evros
    • Alexandroupoli, Evros, Greece, 68100
      • University General Hospital of Alexandroupolis - Department of Neurology
• Italy
  • Baggiovara, Italy
    • Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara
  • Bologna, Italy, 40139
    • IRCCS Istituto delle Scienze Neurologiche di Bologna
  • Brescia, Italy
    • IRCCS - Centro S. Giovanni di Dio Fatebenefratelli
  • Brescia, Italy
    • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
  • Milano, Italy
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Milano, Italy
    • Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta
  • Tricase, Italy
    • PIA Fondazione Panico
  • Emilia Romagna
    • Reggio Emilia, Emilia Romagna, Italy, 42122
      • Azienda Unita Sanita Locale (ASL) di Reggio Emilia - IRCCS
  • Palermo
    • Cefalù, Palermo, Italy, 90015
      • Fondazione Istituto G.Giglio
• Netherlands
  • Rotterdam, Netherlands
    • Erasmus MC
• Portugal
  • Coimbra, Portugal
    • Centro Hospitalar e Universitario de Coimbra EPE
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
  • Lisboa, Portugal
    • Hospital Cuf Descobertas
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto - Hospital de Santo António
• Spain
  • Barcelona, Spain
    • Hospital Clínic de Barcelona
  • Donostia-san Sebastián, Spain
    • Hospital Universitario de Donostia
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marqués de Valdecilla
• Sweden
  • Huddinge, Sweden
    • Karolinska Universitetssjukhuset Huddinge - PPDS
• Switzerland
  • Basel, Switzerland
    • Felix Platter Spital
• Turkey
  • Balcova
    • Izmir, Balcova, Turkey, 35330
      • Dokuz Eylul University
  • Fatih
    • Istanbul, Fatih, Turkey, 34093
      • Istanbul University Medical Faculty
• United Kingdom
  • London, United Kingdom
    • University College London
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Dignity Health
  • California
    • La Jolla, California, United States, 92093-0648
      • University of California San Diego
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University
  • Illinois
    • Evanston, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Neuroscience Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Alzheimer's Disease Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Comprehensive Cancer Center - PPDS
  • New York
    • New York, New York, United States, 10032
      • Irving Institute for Clinical and Translational Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7025
      • University of North Carolina At Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Gardner Neuroscience Institute
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Institute for Academic Medicine
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AL001; AL001 every 4 weeks	Drug: AL001; Administered via intravenous (IV) infusion
Placebo Comparator: Placebo; Placebo every 4 weeks	Drug: Placebo; Administered via intravenous (IV) infusion
Experimental: Open label - AL001; AL001 every 4 weeks	Drug: Open label - AL001; Administered via intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB	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) is administered by a healthcare professional and based on individual ratings of the eight domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, personal care, language and behavior. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 8 individual domain ratings, or "box scores", were added together to give the CDR® plus NACC FTLD-SB which ranges from 0-24. Higher score indicates severe impairment.	Through study completion, on average up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Global Impression-Severity (CGI-S) Score	The CGI-S is used by a clinician to rate the severity of a participant's disease relative to the clinician's past experience with patients who have the same disease using an ordinal scale ranging from 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill patients. Higher scores indicate worsening.	Baseline to 96 weeks
Change in Clinical Global Impression-Improvement (CGI-I) Score	The CGI-I is used by a clinician to rate how much a participant's disease has improved or worsened relative to baseline using an ordinal scale ranging from 1=very much improved; 2=much improved; 3=minimally improved; 4=no change from baseline; 5=minimally worse; 6= much worse; and 7=very much worse. Higher scores indicate worsening.	Baseline to 96 weeks
Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score	RBANS is 20 to 25 minute battery developed for cognitive assessment, detection, and characterization of dementia. RBANS includes 12 subtests that measure following 5 indices: (1)Attention Index, composed of Digit Span and Coding; (2)Language Index, consisting of Picture Naming and Semantic Fluency subtests; (3)Visuospatial/Construction Index, made up of Figure Copy and Line Orientation subtests; (4)Immediate Memory Index, composed of List Learning and Story Memory subtests, and (5)Delayed Memory Index, consisting of List Recall, List Recognition, Story Recall, and Figure Recall subtests. Completion of RBANS yields 5 index scores based on participant performance on various subtests, as well as a composite Total Index score for battery. Total index scores range from 40 to 160, and are normalized to a mean of 100 and standard deviation (SD) of 15. Higher scores indicate less impairment.	Baseline to 96 weeks
Pharmacodynamic Biomarkers	Change in magnetic resonance imaging and blood-based biomarkers and optional CSF biomarkers (neurofilament light chain and progranulin)	Baseline to 96 weeks
Evaluation of safety and tolerability of AL001: Incidence of adverse events	Incidence of adverse events	Baseline to 96 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optional Open-Label Extension	Assess the long-term safety and tolerability of AL001 in participants who have completed 96 week of treatment	96 weeks

Collaborators and Investigators

• Sponsor: Alector Inc.
• Investigators: Principal Investigator: TBD TBD

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): October 11, 2027

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 30, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: AL001-3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No