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

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ClinicalTrials.gov Identifier: NCT04374136
Recruitment Status : Recruiting
First Posted : May 5, 2020
Last Update Posted : July 27, 2020
Sponsor:
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 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




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 48 or 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 48 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 48 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 Frontotemporal Dementia Rating Scale (FRS) Score [ Time Frame: Baseline to 48 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 will be calculated as the number of items with response of "Never" divided by the number items that do not have response of "Not applicable". The percentage score will be converted to a logit score ranging from 5.39 to -6.66 as well as a categorized severity score of Very Mild, Mild, Moderate, Severe, Very Severe, or Profound.

  4. Change in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score [ Time Frame: Baseline to 48 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.

  5. Pharmacodynamic Biomarkers [ Time Frame: Baseline to 48 weeks ]
    Change in magnetic resonance imaging and blood-based biomarkers and optional CSF biomarkers (neurofilament light chain and progranulin)

  6. Evaluation of safety and tolerability of AL001: Incidence of adverse events [ Time Frame: Baseline to 48 weeks ]
    Incidence of adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 of the criteria for the diagnosis of probable behavioral variant FTD, or FTD-semantic subtype or FTD-Progressive nonfluent 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 unresolved cancer.
  • 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 ClinicalTrials.gov identifier (NCT number): NCT04374136


Contacts
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Contact: Study Lead 1-833-346-3383 info@alector.com

Locations
Show Show 47 study locations
Sponsors and Collaborators
Alector Inc.
Investigators
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Principal Investigator: Peter Ljubenkov, MD University of California, San Francisco
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Responsible Party: Alector Inc.
ClinicalTrials.gov Identifier: NCT04374136    
Other Study ID Numbers: AL001-3
First Posted: May 5, 2020    Key Record Dates
Last Update Posted: July 27, 2020
Last Verified: July 2020

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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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Dementia
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
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms