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

Trial Summary

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.

What data supports the effectiveness of the drug BMS-9894923, ALX-001 for Parkinson's Disease?

The research highlights the potential of targeting metabotropic glutamate receptors, like mGluR4, for treating Parkinson's disease symptoms. Similar treatments, such as TAS-4, have shown promise in animal models by improving movement issues without worsening side effects, suggesting that BMS-9894923, ALX-001 might also be effective. ^{1 2 3 4 5}

How is the drug BMS-984923 different from other Parkinson's disease treatments?

BMS-984923 (also known as ALX-001) is unique because it may target specific receptors or pathways not addressed by current Parkinson's treatments, potentially offering a new approach to managing symptoms or side effects like dyskinesia (involuntary movements) associated with long-term use of existing medications like L-DOPA. ^{4 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

Laurie Sanders, Ph.D

Principal Investigator

Duke University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Priorities in Parkinson's disease research. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. New Zealand 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. [2018]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic potential of metabotropic glutamate receptor 4-positive allosteric modulator TAS-4 in rodent models of movement disorders. [2019]

5. Germany 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. [2023]

6. England pubmed.ncbi.nlm.nih.gov

L-745,870 reduces the expression of abnormal involuntary movements in the 6-OHDA-lesioned rat. [2022]

7. United States 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. [2013]

8. England pubmed.ncbi.nlm.nih.gov

New medical and surgical treatments for Parkinson's disease. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Levodopa-induced dyskinesias improved by a glutamate antagonist in Parkinsonian monkeys. [2017]