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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04374136
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : May 6, 2023
Information provided by (Responsible Party):
Alector Inc.

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.

Condition or disease Intervention/treatment Phase
Frontotemporal Dementia Drug: AL001 Drug: Placebo Drug: Open label - AL001 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : July 23, 2020
Estimated Primary Completion Date : October 30, 2023
Estimated Study Completion Date : December 30, 2023

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

Primary Outcome Measures :
  1. Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB [ Time Frame: Through study completion, on average up to 96 weeks ]
    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.

Secondary Outcome Measures :
  1. Change in Clinical Global Impression-Severity (CGI-S) Score [ Time Frame: Baseline to 96 weeks ]
    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. Change in Clinical Global Impression-Improvement (CGI-I) Score [ Time Frame: Baseline to 96 weeks ]
    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. Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score [ Time Frame: Baseline to 96 weeks ]
    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. Pharmacodynamic Biomarkers [ Time Frame: Baseline to 96 weeks ]
    Change in magnetic resonance imaging and blood-based biomarkers and optional CSF biomarkers (neurofilament light chain and progranulin)

  5. Evaluation of safety and tolerability of AL001: Incidence of adverse events [ Time Frame: Baseline to 96 weeks ]
    Incidence of adverse events

Other Outcome Measures:
  1. Optional Open-Label Extension [ Time Frame: 96 weeks ]
    Assess the long-term safety and tolerability of AL001 in participants who have completed 96 week of treatment

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   25 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04374136

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Contact: Study Lead 650-826-2454

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Sponsors and Collaborators
Alector Inc.
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Principal Investigator: TBD TBD
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Responsible Party: Alector Inc. Identifier: NCT04374136    
Other Study ID Numbers: AL001-3
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: May 6, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations