Effect of PXS-4728A on Microglia Activation in Participants With Isolated Rapid Eye Movement Sleep Behaviour Disorder

NCT05904717 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: PXS4728A-IRBD-201
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 3

Brief Summary

This study is to investigate the safety and efficacy of PXS-4728A as an intervention therapy in participants with iRBD. This study will be conducted in participants aged 50 to 80 years of age and will investigate a single dose level.

Conditions

REM Sleep Behavior Disorder

Outcome Measures

Primary Outcomes (2)

• To assess the reduction of microglial activation across striato-cortical regions

  Measured by translocator protein (TSPO) positron emission tomography (PET) imaging.

  Up to Week 12

• To assess the safety and tolerability of PXS-4728A as determined by adverse events (AEs)

  AEs will be coded using the most recent version of MedDRA®

  Up to Week 24

Secondary Outcomes (1)

• To assess the reduction of microglial activation across the whole brain and cortical and subcortical regions of interest (ROIs)

  Up to Week 12

Study Arms (2)

A (PXS-4728)

EXPERIMENTAL

IP Name: PXS-4728 Dosage: 15 mg Mode: oral administration (PO)

Drug: PXS-4728 (A)

B (Matching Placebo)

PLACEBO COMPARATOR

Matching placebo to PXS-4728

Drug: Matching Placebo (B)

Interventions

PXS-4728 (A) DRUG

Participants will receive once daily (QD) for period of 12 weeks

A (PXS-4728)

Matching Placebo (B) DRUG

Participants will receive once daily (QD) for period of 12 weeks

B (Matching Placebo)

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide written informed consent in accordance with GCP, International Council for Harmonisation (ICH) and local regulations.
• Male or female aged 50 to 80 (inclusive) as of the date of Baseline visit.
• Clinical diagnosis of iRBD according to International Classification of Sleep Disorders (ICSD)-3 criteria.
• Objective evidence of 1 or more features of parkinsonism, impaired olfaction and/or impaired color vision discrimination, which have been associated with an increased risk for transitioning to a synucleinopathy in the opinion of the Investigator.
• Screening PET scan demonstrates robust PK11195 signal in striato-cortical region of interest in the opinion of the Investigator.
• Liver Function Tests (LFTs): alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN); total bilirubin ≤ 1.5 × ULN; serum albumin ≥ 2.8 g/dL.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (human chorionic gonadotropin \[hCG\]) at Screening. WOCBP who engage in heterosexual intercourse and men whose sexual partners are WOCBP must agree to use highly effective, double barrier contraception during the study and for a period of 90 days following final dosing. Double barrier contraception is defined as a condom and 1 other form of the following:
• Contraceptive pill
• Depot or injectable birth control
• Intrauterine Device (IUD)
• Contraceptive skin implant, (eg, Implanon NXT®)
• Hormonal vaginal ring, (eg, NuvaRing®)
• Documented evidence of surgical sterilization at least 6 months prior to the Screening visit, (ie, bilateral tubal ligation, oophorectomy, salpingectomy, or total hysterectomy for women or vasectomy for men).
• Must be willing to remain on their current form of contraception for the duration of the study.
• Note: For participants with same-sex partners or who are otherwise abstinent from heterosexual intercourse, total abstinence (defined as abstinence from penile-vaginal intercourse), when this is the preferred and usual lifestyle of participants, may be considered an acceptable form of contraception.

You may not qualify if:

• Meets diagnostic criteria for a degenerative neurologic disorder such as Parkinson's disease, Multiple System Atrophy, Dementia with Lewy Bodies, etc.
• Screening PET scan does not demonstrate robust PK11195 signal in striato-cortical region of interest in the opinion of the Investigator.
• RBD associated with narcolepsy.
• Dementia (Mild Cognitive Impairment permitted).
• Unstable medications (stable use \[minimum 4 weeks\] allowed for treatment of affective symptoms \[mood disorders\] and dream enactment \[eg, melatonin, clonazepam, etc\]).
• Untreated or uncontrolled severe obstructive sleep apnea (OSA).
• Females who are pregnant or breastfeeding.
• Body mass index (BMI) \> 35.0 kg/m2.
• Any known hypersensitivity to the IP, radioligand or their constituents.
• Serious neurological disorder, such as uncontrolled epilepsy or stroke.
• History of psychotic symptoms requiring antipsychotic treatment or exposure to typical or atypical antipsychotics or other dopamine blocking agents within 6 months prior to Screening.
• History of suicidal attempt/s or ideation/s within the prior 6 months.
• Gastrointestinal conditions that may affect the absorption of IP (eg, ulcerative colitis, gastric bypass, or active duodenal or gastric ulcers).
• History of significant medical event/s within 6 months prior to the Screening visit, at the discretion of the PI. This includes, but is not limited to, a cerebrovascular event or a myocardial infarction.
• Any significant uncontrolled cardiac arrhythmia, including but not limited to second and third degree atrioventricular (AV) block.

Sponsors & Collaborators

• Syntara: lead

Study Sites (3)

Parkinsons Disease Research Clinic - Macquarie University

Macquarie, New South Wales, 2109, Australia

Location

Cognitive Neuroscience Brain & Mind Centre

Camperdown, Sydney, 2050, Australia

Location

Clinical Neuroscience Nuffield Department of Clinical Neurosciences

Oxford, United Kingdom

Location

MeSH Terms

Conditions

REM Sleep Behavior Disorder

Condition Hierarchy (Ancestors)

REM Sleep Parasomnias; Parasomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2023
• First Posted: June 15, 2023
• Study Start: November 8, 2023
• Primary Completion: September 30, 2024
• Study Completion: January 31, 2026
• Last Updated: April 11, 2025

Record last verified: 2025-04

Locations

AU (2); GB (1)