---
title: Reduce toxic brain protein clumps
nct_id: NCT06565195
phase: PHASE1
status: RECRUITING
sponsor: Prevail Therapeutics
study_type: INTERVENTIONAL
canonical_url: "https://parkinsonspathways.com/trial/NCT06565195"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT06565195"
last_fetched: "2026-05-10T14:05:33.945Z"
source: "Parkinson's Pathways (curated)"
---
# Reduce toxic brain protein clumps

**Goal (in five words):** Reduce toxic brain protein clumps

**Official Title:** 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

**Trial ID:** [NCT06565195](https://clinicaltrials.gov/study/NCT06565195)

## Key Facts

- **Phase:** PHASE1
- **Status:** RECRUITING
- **Study Type:** INTERVENTIONAL
- **Sponsor:** Prevail Therapeutics
- **Target Enrollment:** 108 participants
- **Start Date:** 2024-08-27
- **Completion Date:** 2029-05-05
- **Conditions:** Parkinson's Disease
- **Interventions:** LY3962681, Placebo (aCSF)
- **Intervention Types:** DRUG, OTHER

## Summary For Families

The goal is to test whether LY3962681 can be safely given into the cerebrospinal fluid and alter alpha-synuclein-related biology that is thought to drive Parkinson's progression, by studying safety, tolerability, and how the drug moves and acts in the body. LY3962681 is an experimental agent delivered by lumbar puncture into the CSF, intended to engage and reduce toxic alpha-synuclein seeds in the brain, and it is being compared to placebo while allowing participants to stay on stable Parkinson medications, including levodopa. The trial enrolls healthy adults for single ascending doses and people with early-stage Parkinson's aged 30 to 80, with Hoehn and Yahr stage 1 to 2.5 OFF, a positive CSF alpha-synuclein assay and supportive tests like DaT-SPECT or smell loss, plus a MoCA of 24 or higher. People with other major neurological diseases, unstable medical conditions, or bleeding risks that would make lumbar puncture unsafe are excluded.

## Eligibility

- **Minimum age:** 30 Years
- **Maximum age:** 80 Years
- **Sex:** ALL

### Full 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.
```

## Locations (4)

- Austin Clinic PPD, Austin, Texas, United States _(30.2672, -97.7431)_
  - Ashley Pham — (CONTACT) — 512-447-2985 — ashley.pham@ppdi.com
- Ehime University Hospital, Tōon, Ehime, Japan _(33.7943, 132.8901)_
- Oita University Hospital, Yufu, Oita Prefecture, Japan _(33.1956, 131.3783)_
- P-One Clinic, Keikokai Medical Corporation, Hachiōji, Tokyo, Japan _(35.6558, 139.3239)_

## Central Contacts

- Prevail Therapeutics — (CONTACT) — 917-336-9310 — Prevail.Patients@lilly.com

---

*Canonical: https://parkinsonspathways.com/trial/NCT06565195*  
*HTML version: https://parkinsonspathways.com/trial/NCT06565195*  
*Source data: https://clinicaltrials.gov/study/NCT06565195*