Phase 1/​2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN) (PROCLAIM) [sponsored by Prevail Therapeutics]

Summary: 

LY3884963 is being developed as a single-dose gene therapy for patients with frontotemporal dementia with GRN mutations (FTD-GRN). Although still unproven, LY3884963 is designed to slow or stop disease progression in FTD-GRN patients by increasing progranulin levels through the delivery of a healthy GRN gene into the central nervous system (CNS). This study is the first use of this new experimental treatment in humans and is designed to assess the safety and efficacy of this experimental treatment.

Who is eligible?

• Men and women aged 30 to 85 years
• Body weight range of 88 lbs to 242 lbs
• Carries a pathogenic progranulin gene (GRN) variant and has symptomatic frontotemporal dementia (FTD), including behavioral-variant FTD, primary progressive aphasia-FTD, FTD with corticobasal syndrome, or a combination of syndromes
• Can walk independently (not dependent on wheelchair or walker)
• Is not living in a nursing home
• Has not had any type of gene therapy
• Has not participated in an FTD clinical trial within the 3 months prior to completing screening for this study
• Has a reliable study partner who can provide information about the participant’s health and functional abilities
• Is able to provide informed consent or has a legally authorized representative who is able to provide informed consent

Individuals meeting these requirements should contact the study coordinator for additional requirements and exclusions if interested in participating.

What will happen during the study?

This study is divided into 4 groups:

Initial cohort:

• Low dose
• Medium dose

Bridging cohort:

• Low dose
• Medium dose

The specific cohort in which a participant is placed will be based on when he/she joins the study.  

Everyone in the study will receive a single dose of the experimental treatment. The experimental treatment will be injected into an area at the base of the skull called the intra cisterna magna. In addition to the single dose of LY3884963, participants will receive methylprednisolone, a corticosteroid used to reduce inflammation, by IV every 2 weeks for the first three months. Participants may also receive additional treatment with other steroids.

​​What are they measuring to evaluate the experimental treatment?

• Side effects and reactions to the experimental treatment
• Changes in progranulin levels in blood and spinal fluid
• Changes in a clinical rating scale called the CDR plus NACC FTLD, which stands for “Clinical Dementia Rating (CDR)+ National Alzheimer's Coordinating Center (NACC) frontotemporal lobar degeneration (FTLD)”

How long will participants be involved in the study?

Study participants will be actively monitored for 12 months.  In addition, participants will be asked to report any undesired and/or unexpected effects of the experimental treatment (adverse events) for four additional years for a total of 5 years of monitoring.