Evaluating LY3962681 in Healthy Volunteers and Parkinson's Disease Patients

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

This study is testing a new drug called LY3962681 to see how safe it is and how it works in both healthy people and those with Parkinson's disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 108 (estimated)
• Ages: 30 Years to 80 Years
• Sex: All
• Sponsor: Prevail Therapeutics (Industry-sponsored)
• Locations: 4 sites (Austin, Texas and 3 other locations)
• Trial ID: NCT06565195 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics of LY3962681 in both healthy volunteers and patients diagnosed with Parkinson's disease. The study consists of two parts: a Single Ascending Dose (SAD) study where healthy participants receive a single dose of the drug or placebo, and a Multiple Ascending Doses (MAD) study where Parkinson's patients receive two doses of the drug or placebo. The treatment will be administered via spinal fluid, with follow-up periods extending up to 52 weeks. The trial seeks to gather data on the drug's effects and safety profile in these populations.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with Parkinson's disease who meet specific clinical criteria and healthy volunteers who are medically evaluated as fit.

Not a fit: Patients with advanced Parkinson's disease or those not meeting the study's eligibility criteria may not benefit from this trial.

Why it matters

Potential benefit: If successful, this study could lead to new treatment options for patients with Parkinson's disease.

How similar studies have performed: While this approach is being explored, similar studies have shown promise in evaluating new treatments for Parkinson's disease, indicating potential for success.

Eligibility criteria

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.
* 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.

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).

Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

Austin, Texas and 3 other locations

• Austin Clinic PPD — Austin, Texas, United States (Recruiting)
• Ehime University Hospital — Tōon, Ehime, Japan (Not_yet_recruiting)
• Oita University Hospital — Yufu, Oita Prefecture, Japan (Not_yet_recruiting)
• P-One Clinic, Keikokai Medical Corporation — Hachiōji, Tokyo, Japan (Recruiting)

Study contacts

• Study coordinator: Prevail Therapeutics

Conditions Parkinson's Disease; Parkinson's disease; Healthy volunteers