A Clinical Trial of LY3962681 in Healthy Volunteers and in Patients With Parkinson's Disease

NCT06565195 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: J5F-MC-OOAA
• Study Type: interventional
• Target: 108
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and PK/PD of LY3962681 in healthy volunteers and patients with Parkinson's disease. The study will be comprised of two parts, the Single Ascending Dose (SAD) study and the Multiple Ascending Doses (MAD) study. During the SAD portion of the study, healthy volunteers will receive a single dose of LY3962681 or placebo (artificial cerebrospinal fluid (aCSF), no active drug) given into the spinal fluid. During the MAD portion of the study, patients with Parkinson's disease will receive two doses of either LY3962681 or placebo (aCSF) administered into the spinal fluid.

• The treatment period in the SAD study will be 1 day. The treatment period in the MAD study will be 2 days, 12 to 24 weeks apart.
• The follow-up period in the SAD study will be up to 52 weeks. The follow-up period in the MAD study will be up to 52 weeks post Dose 2.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Healthy volunteers

Outcome Measures

Primary Outcomes (3)

• Incidence of Serious Adverse Events (SAEs)

  Up to 76 weeks

• Incidence of Treatment Emergent Adverse Events (TEAEs)

  Up to 76 weeks

• Number of discontinuations due to Adverse Events (AEs)

  Up to 76 weeks

Secondary Outcomes (3)

• LY3962681 Maximum Observed Concentration (Cmax)

  Up to 76 weeks

• LY3962681 area under the concentration versus time curve

  Up to 76 weeks

• Change from baseline in CSF total alpha-synuclein

  Up to 76 weeks

Study Arms (2)

LY3962681 (SAD)

EXPERIMENTAL

Single ascending dose of LY3962681 or placebo (aCSF) administered intrathecally (IT) to healthy volunteers.

Drug: LY3962681; Other: Placebo (aCSF)

LY3962681 (MAD)

EXPERIMENTAL

Multiple ascending doses of LY3962681 or placebo (aCSF) administered IT to participants with Parkinson's disease.

Drug: LY3962681; Other: Placebo (aCSF)

Interventions

LY3962681 DRUG

IT injection

LY3962681 (MAD); LY3962681 (SAD)

Placebo (aCSF) OTHER

IT injection

LY3962681 (MAD); LY3962681 (SAD)

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is overtly healthy as determined by medical evaluation. Rescreening is allowed in this study.
• A Montreal Cognitive Assessment score greater than or equal to 24.
• Stable use of background medications at least 8 weeks prior to IP administration, including but not limited to those used for treatment of Parkinson's disease (including deep brain stimulation), and the investigator must expect that participant can tolerate a minimum of 6 months without dose adjustment.
• MAD study only
• Participant has a diagnosis of Parkinson's disease per UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria.
• Modified Hoehn and Yahr Stage 1 to 2.5 in the practically defined OFF state.
• A positive result on CSF alpha-synuclein Seed Amplification Assay. (A prior positive result \[within 1 year of screening\] accepted with sponsor approval if patient did not participate in another Parkinson's disease clinical trial during this period.) (US and Japan only)
• UPSIT score of 10 percentile or less, corrected for age and sex (EU and UK only).
• An abnormal DaT-SPECT consistent with parkinsonism. (History of an abnormal DaTSPECT with the report confirmed by study investigator will be accepted.)
• For participants not taking Parkinson's disease medications, not expected to initiate treatment within 6 months.
• Have a body weight within 40 kg (88 pounds) to 110 kg (242 pounds), inclusive, and body mass index within the range of 17 to 34 kg/m\^2, inclusive.

You may not qualify if:

• MAD study only: Significant neurological disease affecting the central nervous system other than Parkinson's disease that may be a cause for the participant's clinical symptoms or may confound study objectives.
• Current concomitant disease or serious or unstable illnesses, including central nervous system (SAD study only), cardiovascular, hepatic, renal, gastroenterology, respiratory, endocrinologic, neurologic (MAD study only: other than Parkinson's disease), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the conduct of the study or that would, in the opinion of the investigator, pose an unacceptable safety risk to the participant.
• Participant is generally frail or has any medical disorders that, in the opinion of the investigator, could interfere with study-related procedures (including safe performance of IT injection or LP), such as prohibitive spinal diseases, bleeding diathesis, clinically significant coagulopathy, thrombocytopenia, or increased intracranial pressure.
• Have a 12-lead ECG abnormality at screening that, in the opinion of the investigator, increases the risks associated with participating in the study or may confound ECG data analysis.
• MAD study only: Treatment with continuous intestinal delivery Parkinson's disease medication (for example, Duodopa).

Sponsors & Collaborators

• Prevail Therapeutics: lead

Study Sites (4)

Austin Clinic PPD

Austin, Texas, 78744-1625, United States

RECRUITING

Ehime University Hospital

Tōon, Ehime, 791-0295, Japan

NOT YET RECRUITING

Oita University Hospital

Yufu, Oita Prefecture, 879-5593, Japan

NOT YET RECRUITING

P-One Clinic, Keikokai Medical Corporation

Hachiōji, Tokyo, 192-0071, Japan

RECRUITING

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Travis Lewis

  Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Prevail Therapeutics

CONTACT

917-336-9310; Prevail.Patients@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Both the SAD and MAD studies are double blinded (sponsor unblinded); that is, both the participants and the site personnel are blinded to the study intervention.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2024
• First Posted: August 21, 2024
• Study Start: August 27, 2024
• Primary Completion (Estimated): May 5, 2029
• Study Completion (Estimated): May 5, 2029
• Last Updated: January 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); JP (3)