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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04374136




Registration number
NCT04374136
Ethics application status
Date submitted
23/04/2020
Date registered
5/05/2020
Date last updated
6/04/2021

Titles & IDs
Public title
A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)
Scientific 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
Secondary ID [1] 0 0
AL001-3
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Frontotemporal Dementia 0 0
Condition category
Condition code
Neurological 0 0 0 0
Dementias
Neurological 0 0 0 0
Alzheimer's disease
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AL001
Treatment: Drugs - Placebo

Experimental: AL001 - AL001 every 4 weeks

Placebo Comparator: Placebo - Placebo every 4 weeks


Treatment: Drugs: AL001
Administered via intravenous (IV) infusion

Treatment: Drugs: Placebo
Administered via intravenous (IV) infusion

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Through study completion, on average up to 48 or 96 weeks
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Baseline to 48 weeks
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Baseline to 48 weeks
Secondary outcome [3] 0 0
Change in Frontotemporal Dementia Rating Scale (FRS) Score - 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.
Timepoint [3] 0 0
Baseline to 48 weeks
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Baseline to 48 weeks
Secondary outcome [5] 0 0
Pharmacodynamic Biomarkers - Change in magnetic resonance imaging and blood-based biomarkers and optional CSF biomarkers (neurofilament light chain and progranulin)
Timepoint [5] 0 0
Baseline to 48 weeks
Secondary outcome [6] 0 0
Evaluation of safety and tolerability of AL001: Incidence of adverse events - Incidence of adverse events
Timepoint [6] 0 0
Baseline to 48 weeks

Eligibility
Key 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).
Minimum age
25 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [3] 0 0
Perron Institute for Neurological and Translational Science - Subiaco
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
- Subiaco
Recruitment postcode(s) [4] 0 0
- Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Minnesota
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oregon
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Wisconsin
Country [19] 0 0
Belgium
State/province [19] 0 0
Vlaams Brabant
Country [20] 0 0
Canada
State/province [20] 0 0
London
Country [21] 0 0
Canada
State/province [21] 0 0
Toronto
Country [22] 0 0
France
State/province [22] 0 0
Bordeaux
Country [23] 0 0
France
State/province [23] 0 0
Lille
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
Germany
State/province [25] 0 0
Leipzig
Country [26] 0 0
Germany
State/province [26] 0 0
München
Country [27] 0 0
Germany
State/province [27] 0 0
Tübingen
Country [28] 0 0
Germany
State/province [28] 0 0
Ulm
Country [29] 0 0
Italy
State/province [29] 0 0
Baggiovara
Country [30] 0 0
Italy
State/province [30] 0 0
Brescia
Country [31] 0 0
Italy
State/province [31] 0 0
Milano
Country [32] 0 0
Italy
State/province [32] 0 0
Tricase
Country [33] 0 0
Netherlands
State/province [33] 0 0
Rotterdam
Country [34] 0 0
Portugal
State/province [34] 0 0
Coimbra
Country [35] 0 0
Portugal
State/province [35] 0 0
Lisboa
Country [36] 0 0
Spain
State/province [36] 0 0
Barcelona
Country [37] 0 0
Spain
State/province [37] 0 0
Donostia-san Sebastián
Country [38] 0 0
Sweden
State/province [38] 0 0
Huddinge
Country [39] 0 0
Switzerland
State/province [39] 0 0
Basel
Country [40] 0 0
United Kingdom
State/province [40] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alector Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04374136
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Peter Ljubenkov, MD
Address 0 0
University of California, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Lead
Address 0 0
Country 0 0
Phone 0 0
1-833-346-3383
Fax 0 0
Email 0 0
clinicaltrials@alector.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04374136