A Study to Assess the Safety of BMS-984923 Compared to Placebo, in People With Parkinson's

NCT06309147 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ALX-923-107
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1, randomized, double-blind, placebo-controlled study of BMS-984923 administered orally twice daily (BID) for 28 days in participants with Parkinson's disease.

Conditions

Parkinson Disease

Keywords

Synapses; mGluR5 receptor; Silent allosteric modulator; Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (TEAEs)

  Safety

  Up to 14 days after last dose

Secondary Outcomes (1)

• Area under the curve for the first 24 hours of dosing (AUC24h) and at steady state as determined by pharmacokinetic modeling

  Up to 14 days after last dose

Other Outcomes (3)

• To evaluate changes in α-synuclein

  Up to 14 days after last dose

• Change from baseline dopamine transporter

  Up to 3 days after last dose

• Assess changes in motor function

  Up to 14 days after last dose

Study Arms (3)

50 mg Active

EXPERIMENTAL

50mg BID

Drug: BMS-9894923

100mg Active

EXPERIMENTAL

100mg BID

Drug: BMS-9894923

Matching Placebo

PLACEBO COMPARATOR

50 and 100 mg matching placebo

Drug: BMS-9894923

Interventions

BMS-9894923 DRUG

50 mg capsules, oral administration

Also known as: ALX-001

100mg Active; 50 mg Active; 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:

• Men or women between the ages of 50 and 80 years, inclusive at the time of screening.
• Clinical diagnosis of Parkinson's disease as defined by the United Kingdom Parkinson's disease (PD) Society Brain Bank Clinical Diagnostic Criteria and Movement Disorder Society Parkinson's disease Criteria (must meet both criteria); must include bradykinesia and responsiveness to levodopa.
• Maintenance on stable Parkinson's disease therapy for at least 28 days prior to Screening/Visit 1 through treatment period to Day 42, with demonstratable medication efficacy as assessed by the Investigator.
• Severity of Parkinson's disease symptoms assessed by Hoehn and Yahr Staging score ≤3.0 (assessed in the "ON" state).
• Maintenance on permitted stable non-Parkinson's disease therapy for at least 28 days prior to Day 1 through the treatment period to Day 42.
• Female participants of childbearing potential must have a negative urine pregnancy test at Screening and baseline, as well as be non-lactating and must agree to use a highly effective method of contraception during the study and for 30 days following last dose of study drug.
• Male participants must be sterile or sexually inactive or agree not to father a child during the study and for 1 month after the last dose of study medication and must agree to use a barrier method for contraception. Female partners of male subjects must adopt a highly effective method of contraception
• Adequate visual, hearing, cognitive and physical ability and willingness to comply with study drug administration, scheduled visits, treatment plan, laboratory tests, and other study-related procedures to complete the study
• Institutional Review Board/Ethics Committee-approved consent form signed and dated by the participant

You may not qualify if:

• Diagnosis of secondary or atypical parkinsonism
• Severe or disabling fluctuations or dyskinesias that would, in the opinion of the Investigator, interfere with completion of the study
• Previous surgical procedure for Parkinson's disease (e.g. Duopa, deep brain stimulation)
• Clinically significant cognitive impairment with a Montreal Cognitive Assessment score \<18
• Has a history or current evidence of long QT syndrome
• Has bradycardia or tachycardia on the electrocardiogram (ECG) at Screening
• Clinical or laboratory findings consistent with another primary neurodegenerative disease or cognitive disorder other than Parkinson's disease, including but not limited to, frontotemporal lobar disease, Huntington's disease, progressive supranuclear palsy, multisystem atrophy, Jacob-Creutzfeld Disease, Down's syndrome, amyotrophic lateral sclerosis, seizure disorder, or other infectious, metabolic or systemic disease affecting the central nervous system including but not limited to, syphilis, present hypothyroidism, present vitamin B12 deficiency, or other laboratory abnormalities
• Suicidality, defined as active suicidal thoughts or ideation or history of suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious risk of suicide
• Currently active major depression as determined by Beck Depression Inventory (BDI)-II score of \>19
• Has a history or current diagnosis of a psychiatric disorder such as schizophrenia, bipolar disorder or major depression according to the criteria of the most current version of the Diagnostic and Statistical Manual of Mental Disorders.
• Clinically significant or unstable medical condition, including uncontrolled hypertension, or significant cardiac, pulmonary, hepatic, endocrine, or other systemic disease that in the Investigator's opinion may either put the participant at risk because of participation in the study, or influence the results, or impair the participant's ability to participate in the study
• Any disorder that could interfere with absorption, distribution, metabolism or excretion of drugs (e.g., small bowel disease, Crohn's disease, celiac disease or liver disease)
• Hospitalization or change of chronic concomitant medication within 8 weeks prior to baseline
• Body mass index (BMI) \>38 kg/m2 or body weight \<50 kg
• Has uncontrolled type 1 or type 2 diabetes. A subject with glycated hemoglobin (HbA1c) levels up to 7.5% can be enrolled if the Investigator believes the participant's diabetes is under control.

Sponsors & Collaborators

• Allyx Therapeutics: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

Duke Clinical Research Institute

Durham, North Carolina, 27701, United States

RECRUITING

Related Publications (2)

• Ferreira DG, Temido-Ferreira M, Vicente Miranda H, Batalha VL, Coelho JE, Szego EM, Marques-Morgado I, Vaz SH, Rhee JS, Schmitz M, Zerr I, Lopes LV, Outeiro TF. alpha-synuclein interacts with PrPC to induce cognitive impairment through mGluR5 and NMDAR2B. Nat Neurosci. 2017 Nov;20(11):1569-1579. doi: 10.1038/nn.4648. Epub 2017 Sep 25.

  PMID: 28945221 BACKGROUND

• Corbett GT, Wang Z, Hong W, Colom-Cadena M, Rose J, Liao M, Asfaw A, Hall TC, Ding L, DeSousa A, Frosch MP, Collinge J, Harris DA, Perkinton MS, Spires-Jones TL, Young-Pearse TL, Billinton A, Walsh DM. PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins. Acta Neuropathol. 2020 Mar;139(3):503-526. doi: 10.1007/s00401-019-02114-9. Epub 2019 Dec 18.

  PMID: 31853635 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease; Alzheimer Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Tauopathies; Neurocognitive Disorders; Mental Disorders

Study Officials

• Laurie Sanders, Ph.D

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexis Schuettke

CONTACT

919-668-2842; Alexis.schuettke@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double blind, parallel, 3-arm, placebo controlled

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 13, 2024
• Study Start: March 15, 2024
• Primary Completion: February 15, 2025
• Study Completion: July 15, 2025
• Last Updated: March 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)