A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of LY3884963 in Patients With Fronto-Temporal Dementia With Progranulin Mutations (FTD-GRN)
Study J4B-MC-OKAA is a Phase 1/2, multi-center, open-label ascending dose, first-in-human study that will evaluate the safety and effect of intra-cisternal LY3884963 administration on progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin mutations (FTD-GRN). Two escalating dose (low dose and medium dose) cohorts are planned, as well as one bridging cohort which will allocate patients to receive either low or medium dose. The duration of the study is 5 years. During the first year, patients will be evaluated for the effect of LY3884963 on safety, tolerability, immunogenicity, biomarkers, and efficacy. Patients will follow up for an additional 4 years to monitor safety and changes on selected biomarkers and clinical outcomes.
• Men or women aged 30 to 85 years (inclusive), at the time of informed consent.
• Body weight range of ≥40 kg (88 lbs) to ≤110 kg (242 lb) and a BMI of 18 to 34 kg/m2.
• Has symptomatic frontotemporal dementia (FTD), including mild behavioral, cognitive, motor or language impairment per Investigator's assessment (behavioral-variant FTD, primary progressive aphasia-FTD, FTD with corticobasal syndrome, or a combination of syndromes are allowed for enrollment).
• Score ≥0.5 and ≤15 on CDR plus NACC FTLD sum of boxes.
• Stable use of background medications at least 8 weeks prior to LY3884963 dosing.
• Carrier of a pathogenic progranulin gene (GRN) mutation.
• Negative screening test for Mycobacterium tuberculosis (MTB) or documented negative MTB test within 1year prior to screening.
• Age- and gender-appropriate cancer screenings are up-to-date and completed.
• Patient and/or patient's legally authorized representative has the ability to understand the purpose and risks of the study, and provide written informed consent and authorization to use protected health information.
• Patient has a reliable study partner/informant (e.g. family member, friend) willing and able to participate in the study as a source of information on the patient's health status and cognitive and functional abilities.
• Patient is not dependent on a walker or wheelchair.
• Patient is living in the community (i.e. not in nursing home); some levels of assisted living may be permitted at the discretion of the investigator.
• Pneumococcal pneumonia and shingles vaccines are required within 10 years of Screening (allowed to be performed during Screening but must be given at least 4 weeks prior to initiation of immunosuppressant regimen).