BMS-984923 for Parkinson's Disease

Overseen By Alexis Schuettke

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Allyx Therapeutics

Must be taking: Parkinson's therapy

Must not be taking: Anticoagulants, Investigational agents

Disqualifiers: Atypical parkinsonism, Cognitive impairment, Depression, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral medication, BMS-984923, for people with Parkinson's disease. Researchers aim to determine its safety and effectiveness when taken twice daily for 28 days. Participants will receive either 50 mg or 100 mg of the medication or a placebo (a pill with no active ingredient). The trial seeks individuals with Parkinson's who have been on stable treatment for at least 28 days and respond well to their current medication.

As a Phase 1 trial, participants will be among the first to help researchers understand how this new treatment works in people.

Will I have to stop taking my current medications?

The trial requires that you stay on your current Parkinson's disease medications and any other stable non-Parkinson's medications for at least 28 days before starting and throughout the study. However, you cannot take medications that might interact with the study drug during the trial.

Is there any evidence suggesting that BMS-984923 is likely to be safe for humans?

Research has shown that BMS-984923, also known as ALX-001, has undergone testing in earlier studies to ensure its safety for humans. In these studies involving older adults without memory problems, the treatment was safe at all doses tested. Participants tolerated the medicine well, with no serious side effects, which is encouraging for its potential use in treating Parkinson's disease.

The current trial for BMS-984923 is testing two doses, 50 mg and 100 mg, taken twice daily. The aim is to further assess its safety and tolerability in people with Parkinson's disease. As the treatment progresses to more advanced trials, early evidence suggests it is likely safe for humans. However, as with any new treatment, considering possible risks and consulting a doctor before joining the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Researchers are excited about BMS-984923 for Parkinson's disease because it offers a novel mechanism of action compared to traditional treatments like Levodopa or dopamine agonists. Unlike these standard options, which primarily aim to replenish dopamine levels or mimic its effects, BMS-984923 targets a different pathway that could potentially modify the disease's progression. Additionally, it comes in two dosages, 50 mg and 100 mg, allowing for tailored treatment approaches. By exploring this new pathway, BMS-984923 holds the promise of providing more effective symptom management and possibly slowing down the progression of Parkinson's disease.

What evidence suggests that BMS-984923 might be an effective treatment for Parkinson's disease?

Research shows that BMS-984923, also known as ALX-001, interacts with a specific part of the brain, potentially alleviating symptoms of Parkinson’s disease. In earlier studies, this treatment improved memory and brain connections in mice with Alzheimer's disease. Although these results are promising, researchers are still in the early stages of understanding BMS-984923's effectiveness for Parkinson’s disease in humans. This trial includes different treatment arms, with participants receiving either 50 mg or 100 mg of BMS-984923, or a matching placebo. Initial studies focus on its safety and tolerability over a 28-day period. ^{1 2 3 4 6}

Who Is on the Research Team?

Laurie Sanders, Ph.D

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

Adults aged 50-80 with Parkinson's disease, able to follow the study plan and on stable PD therapy. They must not have severe symptoms, cognitive impairment, or a history of certain medical conditions. Participants need to use effective contraception if they can have children.

Inclusion Criteria

Institutional Review Board/Ethics Committee-approved consent form signed and dated by the participant

My Parkinson's symptoms are mild to moderate.

I have been diagnosed with Parkinson's disease and respond to levodopa.

Exclusion Criteria

Suspected or known allergy to any components of the study medication

Thrombocytopenia defined as platelet count <100,000/microliter

Neutropenia defined as absolute neutrophil count of <1,500/microliter

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-984923 or placebo orally twice daily for 28 days

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-9894923

Trial Overview The trial is testing BMS-9894923, an oral medication taken twice daily for 28 days against a placebo in people with Parkinson's Disease to see its effects and safety.

How Is the Trial Designed?

Group I: 50 mg Active Experimental Treatment 1 Intervention

50mg BID

Group II: 100mg Active Experimental Treatment 1 Intervention

100mg BID

Group III: Matching Placebo Placebo Group 1 Intervention

50 and 100 mg matching placebo

Who Is Running the Clinical Trial?

Allyx Therapeutics

Lead Sponsor

Trials

4

Recruited

120+

Michael J. Fox Foundation for Parkinson's Research

Collaborator

Trials

117

Recruited

537,000+

Published Research Related to This Trial

The Phase I clinical trial of PF-06669571, a novel dopamine D1 receptor partial agonist, demonstrated that the drug was safe and well tolerated in 20 subjects with Parkinson's disease, with no serious safety concerns reported.

Although the primary endpoint for significant improvement in motor symptoms did not meet pre-specified criteria, a sensitivity analysis suggested potential efficacy, particularly when excluding an outlier with a very high L-DOPA dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Novel Dopamine D1 Receptor Partial Agonist, PF-06669571, in Subjects with Idiopathic Parkinson's Disease. Gurrell, R., Duvvuri, S., Sun, P., et al.[2018]

LY-404,039 significantly reduced dyskinesia by 55% and psychosis-like behaviors by 50% in MPTP-lesioned marmosets when combined with L-DOPA, indicating its potential efficacy in treating Parkinson's disease symptoms.

The study suggests that LY-404,039, which also acts on dopamine D2 receptors, may offer broader therapeutic benefits compared to other mGluR2/3 agonists, supporting its potential repurposing for Parkinson's disease treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The mGluR2/3 orthosteric agonist LY-404,039 reduces dyskinesia, psychosis-like behaviours and parkinsonism in the MPTP-lesioned marmoset. Kang, W., Nuara, SG., Bédard, D., et al.[2023]

In a study involving L-DOPA-primed rats, the dopamine D4 receptor antagonist L-745,870 significantly reduced L-DOPA-induced abnormal involuntary movements (AIMs) by 84% at a dose of 1 mg/kg, indicating its potential as an antidyskinetic agent.

However, L-745,870 did not improve motor performance on the rotarod test, suggesting that while it alleviates dyskinesia, it may compromise the antiparkinsonian effects of L-DOPA in this rat model, indicating a narrow therapeutic window for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-745,870 reduces the expression of abnormal involuntary movements in the 6-OHDA-lesioned rat. Huot, P., Johnston, TH., Koprich, JB., et al.[2022]

The study evaluated the mGluR4 positive allosteric modulator TAS-4 in rodent models of Parkinson's disease, showing it effectively reversed symptoms like catalepsy and enhanced the effects of l-DOPA without increasing side effects.

TAS-4, when combined with a low dose of l-DOPA, provided similar antiparkinsonian benefits to a higher dose of l-DOPA, suggesting it could improve treatment outcomes while minimizing adverse motor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of metabotropic glutamate receptor 4-positive allosteric modulator TAS-4 in rodent models of movement disorders. Dube, A., Chaudhary, S., Mengawade, T., et al.[2019]

Current dopamine replacement therapies can alleviate motor symptoms of Parkinson's disease, but there is a significant need for improved treatments that also address non-motor symptoms and provide neuroprotection.

Research is focusing on identifying promising biological targets and therapeutic agents, with an emphasis on understanding genetic factors and enhancing the translation of findings from animal models to human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Priorities in Parkinson's disease research. Meissner, WG., Frasier, M., Gasser, T., et al.[2022]

Motor fluctuations and dyskinesias are common and debilitating complications in Parkinson's disease patients within the first few years of treatment, significantly impacting their quality of life.

New therapeutic options, such as subcutaneous apomorphine and deep-brain stimulation, are available for patients who continue to experience motor complications despite optimal medical management, potentially improving both motor and nonmotor symptoms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of motor complications in Parkinson disease: current and emerging therapies. Espay, AJ.[2013]

In a study involving six macaques with L-DOPA-induced dyskinesia, the dopamine D(4) receptor antagonist L-745,870 significantly reduced dyskinesia severity by up to 59% when combined with L-DOPA, without affecting the overall antiparkinsonian benefits.

L-745,870 also increased the duration of 'ON-time' without disabling dyskinesia by 204%, suggesting it could be a promising therapeutic option for managing L-DOPA-induced dyskinesia in Parkinson's disease, with a favorable safety profile based on previous clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

L-745,870 reduces L-DOPA-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease. Huot, P., Johnston, TH., Koprich, JB., et al.[2013]

COMT inhibitors have been shown to effectively prolong the action of levodopa in Parkinson's disease patients experiencing the 'wearing off' phenomenon, providing a new treatment option for those with fluctuating responses to standard therapy.

Clozapine not only alleviates levodopa-induced psychosis but also helps reduce tremors and dyskinesias, highlighting its dual role in managing symptoms of Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New medical and surgical treatments for Parkinson's disease. Klockgether, T., Löschmann, PA., Wüllner, U.[2019]

The NMDA receptor antagonist LY235959 significantly reduced oral dyskinesias by 68% and diminished choreic dyskinesias in a study involving six monkeys with Parkinson's disease, indicating its potential to alleviate side effects of long-term levodopa therapy.

Importantly, LY235959 did not impair the antiparkinsonian effects of levodopa, suggesting that NMDA receptor blockade could be a safe and effective strategy to manage dyskinesias without compromising the treatment of Parkinson's symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. Papa, SM., Chase, TN.[2017]

Citations

1. dcri.org dcri.org/news/first-parkinsons-disease-patient-treated-alx-001-allyx-therapeutics-dcri-study

First Parkinson's Disease Patient Treated with ALX-001 in ... The 28-day Parkinson's disease study (NCT06309147) is assessing the safety of ALX-001 dosed twice daily at either 50 mg or 100 mg versus placebo ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06309147

NCT06309147 | A Study to Assess the Safety of BMS- ... This research study will assess the safety and tolerability of multiple doses of BMS-984923 for the treatment of early Parkinson's disease and investigate ...

3. neurologylive.com neurologylive.com/view/alx001-advance-phase-2-studies-following-positive-phase-1b-mad-data

ALX001 to Advance to Phase 2 Studies Following Positive ... Building on positive phase 1a data, ALX-001 demonstrated target engagement of mGluR5 receptor and maintained a safe profile across multiple ...

4. withpower.com withpower.com/trial/phase-1-parkinson-disease-2-2024-481d5

BMS-984923 for Parkinson's Disease This Phase 1 medical study run by Allyx Therapeutics is evaluating whether BMS-9894923 will have tolerable side effects & efficacy for patients with ...

5. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/BMS-984923_%28ALX-001%29_UPDATE_%28drug_in_development%29.pdf

BMS-984923 (ALX-001) BMS-984923 restores cognitive deficits and synaptic loss in mouse models of Alzheimer's disease. Early phase clinical trials are currently ongoing.

6. ddw-online.com ddw-online.com/early-trial-data-supports-neurodegenerative-disease-modifying-drug-28941-202403/

Trial supports neurodegenerative disease-modifying drug Study results show that ALX-001 was safe in cognitively normal older adults at all tested doses. ALX-001 achieved high exposure and successfully ...