A Clinical Trial of LY3962681 in Healthy Volunteers and in Patients With Parkinson's Disease (PROSPECT-PD)

August 27, 2026 updated by: Prevail Therapeutics

A Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled, Single-ascending-dose Study in Healthy Volunteers and a Double-blind (Sponsor-unblinded), Placebo-controlled, Multiple-ascending-dose Study in Patients With Parkinson's Disease to Evaluate the Safety, Tolerability, and PK/PD of LY3962681

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of LY3962681 in healthy volunteers and patients with Parkinson's disease.

The study consists of two parts, the Single Ascending Dose (SAD) study and the Multiple Ascending Dose (MAD) study.

During the SAD portion of the study, healthy volunteers will receive a single dose of LY3962681 or placebo (artificial cerebrospinal fluid [aCSF]) administered intrathecally (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 intrathecally (into the spinal fluid), 12 to 24 weeks apart.

  • The treatment period in the SAD study will be 1 day. The treatment period in the MAD study will be 2 dosing 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 after Dose 2.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

124

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Germany
    • North Rhine-Westphalia
      • Düsseldorf, North Rhine-Westphalia, Germany, 40225
        • Not yet recruiting
        • Universitätsklinikum Düsseldorf
      • Münster, North Rhine-Westphalia, Germany, 48149
        • Not yet recruiting
        • Universitätsklinikum Münster
  • Japan
    • Ehime
      • Tōon, Ehime, Japan, 791-0295
    • Oita Prefecture
      • Yufu, Oita Prefecture, Japan, 879-5593
        • Not yet recruiting
        • Oita University Hospital
        • Contact:
    • Tokyo
      • Hachiōji, Tokyo, Japan, 192-0071
        • Recruiting
        • P-One Clinic, Keikokai Medical Corporation
        • Contact:
  • Netherlands
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Not yet recruiting
        • Radboud Universitair Medisch Centrum
        • Contact:
          • Bas Bloem
    • Provincie Groningen
      • Groningen, Provincie Groningen, Netherlands, 9713 GZ
  • United Kingdom
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6TH
        • Not yet recruiting
        • Southampton General Hospital, NHS Trust
    • Oxfordshire
      • Oxford, Oxfordshire, United Kingdom, OX3 9DU
        • Not yet recruiting
        • John Radcliffe Hospital
  • United States
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Not yet recruiting
        • CenExel
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Not yet recruiting
        • XingImaging LLC
    • Florida
      • Naples, Florida, United States, 34105
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Not yet recruiting
        • Northwestern University Feinberg School of Medicine Dept of Neurology
    • Michigan
      • Farmington Hills, Michigan, United States, 48334
        • Not yet recruiting
        • Quest Research Institute - Alcanza
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Not yet recruiting
        • University of Pennsylvania, Dept of Neurology
    • Texas
      • Austin, Texas, United States, 78744-1625
        • Completed
        • Austin Clinic PPD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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.

MAD study only

  • 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.
  • 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 20 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.

Exclusion Criteria:

  • 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).
  • MAD study only: Significant renal impairment (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m^2).

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LY3962681 (SAD)
Single ascending dose of LY3962681 administered intrathecally (IT) to healthy volunteers.
Drug: LY3962681
IT injection
Placebo Comparator: Placebo (SAD)
Single ascending dose of placebo (aCSF) administered intrathecally (IT) to healthy volunteers.
Other: Placebo (aCSF)
IT injection
Experimental: LY3962681 (MAD)
Multiple ascending doses of LY3962681 administered IT to participants with Parkinson's disease.
Drug: LY3962681
IT injection
Placebo Comparator: Placebo (MAD)
Multiple ascending doses of placebo (aCSF) administered IT to participants with Parkinson's disease.
Other: Placebo (aCSF)
IT injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of Serious Adverse Events (SAEs)
Time Frame: Up to 76 weeks
Up to 76 weeks
Incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame: Up to 76 weeks
Up to 76 weeks
Number of discontinuations due to Adverse Events (AEs)
Time Frame: Up to 76 weeks
Up to 76 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
LY3962681 Maximum Observed Concentration (Cmax)
Time Frame: Up to 76 weeks
Up to 76 weeks
Change from baseline in CSF total alpha-synuclein
Time Frame: Up to 76 weeks
Up to 76 weeks
LY3962681 area under the concentration versus time curve (AUC)
Time Frame: Up to 76 weeks
Up to 76 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Prevail Therapeutics

Investigators

  • Study Director: Travis Lewis, Prevail Therapeutics, a Wholly Owned Subsidiary of Eli Lilly and Company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 27, 2024

Primary Completion (Estimated)

July 23, 2030

Study Completion (Estimated)

July 23, 2030

Study Registration Dates

First Submitted

August 19, 2024

First Submitted That Met QC Criteria

August 19, 2024

First Posted (Actual)

August 21, 2024

Study Record Updates

Last Update Posted (Actual)

September 1, 2026

Last Update Submitted That Met QC Criteria

August 27, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • J5F-MC-OOAA
  • 2024-513411-27-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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