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

Phase 3TerminatedNCT04374136

Alector Inc.119 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

119

Conditions

Frontotemporal Dementia

Interventions

Part 1 Blinded - AL001DRUG

Administered via intravenous (IV) infusion

Part 1 Blinded - PlaceboDRUG

Administered via intravenous (IV) infusion

Part 2 (OLE Treatment) - AL001DRUG

Administered via intravenous (IV) infusion

Eligibility

Sex: ALLMin age: 25 YearsMax age: 85 Years

Medical Language ↔ Plain English

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, unless in remission or stable/adequately controlled. * 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.

Locations (44)

Outcomes

Primary Outcomes

Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo as Measured by the CDR® Plus NACC FTLD-SB in Symptomatic Patients

Part 1 Primary Endpoint - Change from baseline to Weeks 48, 72, and 96 in 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.

Time frame: Through study completion, on average up to 96 weeks

Part 1 Double Blind (Co-Primary US Endpoint) - Evaluation of the Treatment Effect of AL001 Compared With Placebo as Measured by Pharmacodynamic and Disease Pathology Biomarkers in Symptomatic Patients

Geometric Mean Fold Change from baseline to Week 96 in PGRN concentrations in plasma

Time frame: Baseline to 96 weeks

Part 2 OLE - To Assess the Long-term Safety and Tolerability of AL001 in Participants Who Have Completed Part 1 of the Study

Part 2 OLE Primary Endpoint - Incidence, nature, and severity of AEs and SAEs in Part 2 OLE

Time frame: 96 weeks

Secondary Outcomes

Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-S

Change from baseline to Weeks 48, 72, and 96 on the CGI-S. 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.

Data from ClinicalTrials.gov

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Dignity Health

Phoenix, Arizona, United States

University of California San Diego

La Jolla, California, United States

University of Colorado

Aurora, Colorado, United States

Emory University

Atlanta, Georgia, United States

Indiana University Health Neuroscience Center

Indianapolis, Indiana, United States

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Mayo Comprehensive Cancer Center - PPDS

Rochester, Minnesota, United States

Irving Institute for Clinical and Translational Research

New York, New York, United States

University Of Cincinnati Gardner Neuroscience institute

Cincinnati, Ohio, United States

...and 34 more locations

Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score

Change from baseline to Weeks 48, 72, and 96 on the RBANS. 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.

Time frame: Baseline to 96 weeks