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

• Sponsor: Alector Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04374136
• Collaborator: (none)
• Enrollment: 180
• Locations: 47
• Arms: 3
• Anticipated Duration (Months): 41.2
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Anticipated 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: Jul 23, 2020
• Anticipated Primary Completion Date: Oct 30, 2023
• Anticipated Study Completion Date: Dec 30, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Evaluation of efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB [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 [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 [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 [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 [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 [Baseline to 96 weeks]

   Incidence of adverse events

Other Outcome Measures

1. Optional Open-Label Extension [96 weeks]

   Assess the long-term safety and tolerability of AL001 in participants who have completed 96 week of treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 85 Years
• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dignity Health	Phoenix	Arizona	United States	85013
2	University of California San Diego	La Jolla	California	United States	92093-0648
3	University of California San Francisco	San Francisco	California	United States	94143
4	University of Colorado	Aurora	Colorado	United States	80045
5	University of Miami Medical Center	Miami	Florida	United States	33136
6	Emory University	Atlanta	Georgia	United States	30329
7	Northwestern University	Evanston	Illinois	United States	60611
8	Indiana University Health Neuroscience Center	Indianapolis	Indiana	United States	46202
9	University of Kansas Alzheimer's Disease Center	Fairway	Kansas	United States	66205
10	Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21205
11	Mayo Comprehensive Cancer Center - PPDS	Rochester	Minnesota	United States	55905
12	Irving Institute for Clinical and Translational Research	New York	New York	United States	10032
13	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7025
14	University Of Cincinnati Gardner Neuroscience institute	Cincinnati	Ohio	United States	45219
15	Case Western Reserve University	Cleveland	Ohio	United States	44106
16	Oregon Health and Science University	Portland	Oregon	United States	97239
17	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
18	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
19	Houston Methodist Institute for Academic Medicine	Houston	Texas	United States	77030
20	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
21	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
22	Box Hill Hospital	Box Hill		Australia	3128
23	Royal Prince Alfred Hospital	Camperdown		Australia	2050
24	Perron Institute for Neurological and Translational Science	Subiaco		Australia
25	The Queen Elizabeth Hospital	Woodville		Australia
26	UZ Leuven	Leuven	Vlaams Brabant	Belgium	3000
27	The University of Western Ontario	London		Canada
28	Sunnybrook Research Institute - University of Toronto	Toronto		Canada
29	CHU de Bordeaux	Bordeaux		France
30	CHRU Lille	Lille		France
31	Groupe Hospitalier Pitié Salpétrière	Paris		France
32	Klinikum rechts der Isar der Technischen Universität München	München		Germany
33	Universitätsklinikum Ulm	Ulm		Germany
34	Nuovo Ospedale Civile S. Agostino-Estense di Baggiovara	Baggiovara		Italy
35	ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia	Brescia		Italy
36	IRCCS - Centro S. Giovanni di Dio Fatebenefratelli	Brescia		Italy
37	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano		Italy
38	Fondazione IRCCS Di Rilievo Nazionale Istituto Nazionale Neurologico Carlo Besta	Milano		Italy
39	PIA Fondazione Panico	Tricase		Italy
40	Erasmus MC	Rotterdam		Netherlands
41	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra		Portugal
42	Hospital CUF Descobertas	Lisboa		Portugal
43	Hospital Clinic de Barcelona	Barcelona		Spain
44	Hospital Universitario de Donostia	Donostia-san Sebastián		Spain
45	Karolinska Universitetssjukhuset Huddinge - PPDS	Huddinge		Sweden
46	Felix Platter Spital	Basel		Switzerland
47	University College London	London		United Kingdom

Sponsors and Collaborators

• Alector Inc.

Investigators

• Principal Investigator: Peter Ljubenkov, MD, University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alector Inc.
• ClinicalTrials.gov Identifier: NCT04374136
• Other Study ID Numbers: AL001-3
• First Posted: May 5, 2020
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain

Study Results

No Results Posted as of Aug 23, 2022