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Terminated

NCT Number: NCT04374136

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

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.

Why the study stopped: The trial did not meet the clinical co-primary endpoint of slowing FTD-GRN progression, as measured by the Clinical Dementia Rating® plus National Alzheimer's Coordinating Center Frontotemporal Lobar Degeneration Sum of Boxes (CDR® plus NACC FTLD-SB)
Terminated

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Key information

Conditions

Frontotemporal Dementia Brain Diseases Central Nervous System Diseases Dementia Frontotemporal Lobar Degeneration Mental Disorders Metabolic Diseases Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies TDP-43 Proteinopathies

Age range

25 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Fundación Para La Lucha Contra Las Enfermedades Neurológicas de La Infancia, Buenos Aires, Argentina

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Part 1 Blinded - AL001

Drug

Administered via intravenous (IV) infusion

Part 1 Blinded - Placebo

Drug

Administered via intravenous (IV) infusion

Part 2 (OLE Treatment) - AL001

Drug

Administered via intravenous (IV) infusion

Part 2 (OLE Treatment) - Placebo Switched to AL001

Drug

Administered via intravenous (IV) infusion

Primary outcomes

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

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

    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.

  2. 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

    Time frame: Baseline to 96 weeks

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

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

    Time frame: 96 weeks

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

Secondary outcomes

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

    Time frame: Baseline to 96 weeks

    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.

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

    Time frame: Baseline to 96 weeks

    Actual values at Weeks 48, 72, and 96 on the CGI-I. 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.

  3. 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

    Time frame: Baseline to 96 weeks

    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.

  4. Part 1 Double Blind - Evaluation of the Safety and Tolerability of AL001 Compared With Placebo as Measured by Safety Assessments

    Time frame: Baseline to 96 weeks

    Incidence of adverse events

  5. Part 1 Double Blind: Clinical Progression as Measured by Frontotemporal Dementia Rating Scale (FRS) Logit Score in Symptomatic Participants

    Time frame: baseline to 96 weeks

    The FRS is a 30-item scale with item responses of 'All the time,' 'Sometimes,' 'Never,' or 'Not applicable' for each item. The total percentage score is calculated as the number of items with a response of 'Never,' divided by the number of applicable items, excluding those marked 'not applicable.' The percentage score ranges from 0 to 100, inclusive, with higher scores indicating better function (fewer behavioral/functional problems) and lower scores indicating worse function. The percentage score is converted to a logit score ranging from -6.66 to 5.39 using a look-up table defined as part of the FRS instrument, where a higher (more positive) logit score indicates better function/less disease severity (5.39 = normal) and a lower (more negative) logit score indicates worse function/greater disease severity (-6.66 = advanced/profound impairment). A decrease in logit score over time reflects clinical progression

Interested in participating?

Terminated

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Sponsors and collaborators

Lead sponsor

Alector Inc.

Industry

Collaborators

  • GlaxoSmithKline

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2025
Study completion
2026
First posted
May 5, 2020
Registry last updated
Sep 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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