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
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Alector Inc.
- Enrollment
- 119
- Locations
- 44
- Primary Endpoint
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo as Measured by the CDR® Plus NACC FTLD-SB in Symptomatic Patients
Study Overview
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.
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 completion marks the end of the open label extension period following the 96-week blinded portion of the study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 25 Years to 85 Years (Adult, Older Adult)
- Sex
- 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, 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.
Arms & Interventions
Part 2 (OLE Treatment) - Placebo Switched to AL001
Participants who received placebo during the double-blind treatment period and enroll in the optional open-label extension receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks.
Intervention: Part 2 (OLE Treatment) - Placebo Switched to AL001 (Drug)
Part 1 Blinded - AL001
Participants receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period.
Intervention: Part 1 Blinded - AL001 (Drug)
Part 1 Blinded - Placebo
Participants receive placebo administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period.
Intervention: Part 1 Blinded - Placebo (Drug)
Part 2 (OLE Treatment) - AL001
Participants who received AL001 during the double-blind treatment period and enroll in the optional open-label extension receive AL001 60 mg/kg administered by intravenous (IV) infusion every 4 weeks.
Intervention: Part 2 (OLE Treatment) - AL001 (Drug)
Outcomes
Primary Outcomes
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.
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
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
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-S(Baseline to 96 weeks)
- Part 1 Double Blind - Evaluation of Efficacy of AL001 Compared With Placebo in Symptomatic Participants as Measured by CGI-I(Baseline to 96 weeks)
- 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(Baseline to 96 weeks)
- Part 1 Double Blind - Evaluation of the Safety and Tolerability of AL001 Compared With Placebo as Measured by Safety Assessments(Baseline to 96 weeks)
- Part 1 Double Blind: Clinical Progression as Measured by Frontotemporal Dementia Rating Scale (FRS) Logit Score in Symptomatic Participants(baseline to 96 weeks)