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

Frontotemporal Dementia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04374136
• Other study ID #: AL001-3
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 23, 2020
• Est. completion date: October 11, 2027

Study information

• Verified date: May 2024
• Source: Alector Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 110
• Est. completion date: October 11, 2027
• Est. primary completion date: September 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Dementia
• Frontotemporal Dementia
• Pick Disease of the Brain

Intervention

Drug:
• AL001
Administered via intravenous (IV) infusion
• Placebo
Administered via intravenous (IV) infusion
• Open label - AL001
Administered via intravenous (IV) infusion

Locations

Country	Name	City	State
Argentina	Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia	Buenos Aires
Argentina	CENydET S.R.L.	Retiro	Ciudad Autónoma De BuenosAires
Argentina	INECO Castaño	San Juan
Australia	Box Hill Hospital	Box Hill
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	The Queen Elizabeth Hospital	Woodville
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Canada	The University of Western Ontario	London
Canada	Sunnybrook Research Institute - University of Toronto	Toronto
France	CHU de Bordeaux	Bordeaux
France	CHRU Lille	Lille
France	Groupe Hospitalier Pitié Salpétrière	Paris
France	Hopital Charles Nicolle - Hospital	Rouen	Seinne-Maritime
France	CHU de Toulouse Hopital PURPAN	Toulouse	Haute-Garonne
Germany	Uniklinik Köln	Köln
Germany	Universitätsklinikum Ulm	Ulm
Greece	University General Hospital of Alexandroupolis - Department of Neurology	Alexandroupoli	Evros
Greece	Eginitio University General Hospital of Athens - 1st University Neurology Clinic	Athens	Attica
Italy	Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara	Baggiovara
Italy	IRCCS Istituto delle Scienze Neurologiche di Bologna	Bologna
Italy	ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia	Brescia
Italy	IRCCS - Centro S. Giovanni di Dio Fatebenefratelli	Brescia
Italy	Fondazione Istituto G.Giglio	Cefalù	Palermo
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano
Italy	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta	Milano
Italy	Azienda Unita Sanita Locale (ASL) di Reggio Emilia - IRCCS	Reggio Emilia	Emilia Romagna
Italy	PIA Fondazione Panico	Tricase
Netherlands	Erasmus MC	Rotterdam
Portugal	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria	Lisboa
Portugal	Hospital CUF Descobertas	Lisboa
Portugal	Centro Hospitalar do Porto - Hospital de Santo António	Porto
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitario de Donostia	Donostia-san Sebastián
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Sweden	Karolinska Universitetssjukhuset Huddinge - PPDS	Huddinge
Switzerland	Felix Platter Spital	Basel
Turkey	Istanbul University Medical Faculty	Istanbul	Fatih
Turkey	Dokuz Eylul University	Izmir	Balcova
United Kingdom	University College London	London
United States	Emory University	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University Of Cincinnati Gardner Neuroscience institute	Cincinnati	Ohio
United States	Case Western Reserve University	Cleveland	Ohio
United States	University of Kansas Alzheimer's Disease Center	Fairway	Kansas
United States	Houston Methodist Institute for Academic Medicine	Houston	Texas
United States	Indiana University Health Neuroscience Center	Indianapolis	Indiana
United States	University of California San Diego	La Jolla	California
United States	University of Miami Medical Center	Miami	Florida
United States	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Irving Institute for Clinical and Translational Research	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Dignity Health	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Mayo Comprehensive Cancer Center - PPDS	Rochester	Minnesota
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Alector Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Optional Open-Label Extension	Assess the long-term safety and tolerability of AL001 in participants who have completed 96 week of treatment	96 weeks
Primary	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	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
Secondary	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
Secondary	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
Secondary	Pharmacodynamic Biomarkers	Change in magnetic resonance imaging and blood-based biomarkers and optional CSF biomarkers (neurofilament light chain and progranulin)	Baseline to 96 weeks
Secondary	Evaluation of safety and tolerability of AL001: Incidence of adverse events	Incidence of adverse events	Baseline to 96 weeks