What is the mechanism of action of this treatment?

Common treatments for Parkinson's Disease (PD) include levodopa, dopamine agonists, MAO-B inhibitors, and amantadine. Levodopa is converted to dopamine in the brain, replenishing the diminished dopamine levels characteristic of PD. Dopamine agonists mimic dopamine by stimulating dopamine receptors. MAO-B inhibitors prevent the breakdown of dopamine, thereby increasing its availability. Amantadine helps reduce symptoms by modulating glutamate activity. These treatments are crucial as they address the core issue of dopamine deficiency, improving motor function and quality of life for PD patients. BIA 28-6156, which targets the glucocerebrosidase pathway, aims to enhance the degradation of misfolded proteins, potentially offering a disease-modifying approach by addressing underlying cellular dysfunctions.

What side effects are associated with this type of intervention?

Common treatments for Parkinson's Disease, such as levodopa, dopamine agonists (DAs), and MAO B inhibitors, often come with side effects. Levodopa can cause nausea, orthostatic hypotension, confusion, hallucinations, and motor complications like dyskinesia. Dopamine agonists may lead to nausea, somnolence, dizziness, and compulsive behaviors. MAO B inhibitors generally have fewer side effects but can still cause nausea and orthostatic hypotension. Cholinesterase inhibitors, used for cognitive impairment in PD, can worsen tremors and cause nausea. These side effects are important considerations when managing PD treatment plans.

What prior FDA approvals exist?

FDA-approved treatments for Parkinson's Disease primarily include dopaminergic therapies such as levodopa, dopamine agonists, and MAO-B inhibitors. Levodopa is often combined with carbidopa to enhance its efficacy and reduce side effects. Dopamine agonists like pramipexole and ropinirole mimic dopamine's effects in the brain. MAO-B inhibitors, such as selegiline and rasagiline, help prevent the breakdown of dopamine. While there are no specific FDA-approved treatments targeting the glucocerebrosidase pathway for Parkinson's Disease, ongoing research, including the trial of BIA 28-6156, aims to explore this potential therapeutic avenue.

What other types of research exist?

Promising novel alternatives to BIA 28-6156 for Parkinson's Disease patients include: 1) LY344864, which stimulates mitochondrial biogenesis and attenuates dopaminergic neuron loss; 2) S-181, a small-molecule modulator of glucocerebrosidase that restores lysosomal function and reduces α-synuclein accumulation; 3) GM1 ganglioside, which decreases α-synuclein accumulation and alleviates mitochondrial dysfunction; 4) UCP0054278, which interacts with DJ-1 to produce antioxidant effects and prevent dopaminergic neural cell death; and 5) ACS84, a hydrogen sulfide-releasing L-Dopa derivative that alleviates movement dysfunction and dopaminergic neuron loss.

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Enzyme Inhibitor

BIA 28-6156 for Parkinson's Disease (ACTIVATE Trial)

Verified Trial

Phase 2

Recruiting

Research Sponsored by Bial R&D Investments, S.A.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

- The subject is ≥35 and ≤80 years of age at the time of informed consent.

- The subject has a modified Hoehn and Yahr score ≤2.5.

Must not have

Individuals who do not satisfy the inclusion criteria for Part A (Genetic Screening) will be excluded.

- The subject has Gaucher's disease (GD), as defined by clinical signs and symptoms (i.e., hepatosplenomegaly, cytopenia, skeletal disease), and/or a medical history of marked deficiency of GCase activity compatible with GD.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from baseline up to week 78

Summary

This trial is testing a new drug called BIA 28-6156 to see if it can slow down movement problems in people with Parkinson's disease who have a specific genetic mutation. The study will compare the drug to another treatment over a period of several months.

Who is the study for?

This trial is for adults aged 35-80 with Parkinson's disease (PD) diagnosed between 1 and 7 years, carrying a specific GBA1 gene variant but not Gaucher's disease. They must have mild to moderate PD severity, stable PD medication use, no severe motor issues or surgery plans that could affect the study, and agree to birth control if applicable. Excluded are those with atypical parkinsonism, substance abuse history, certain medical conditions or treatments that might interfere with the study.

What is being tested?

The trial tests BIA 28-6156 (10 mg or 60 mg) against a placebo in delaying motor progression over 78 weeks in patients with GBA-PD. It's randomized and double-blind meaning neither participants nor researchers know who receives the drug or placebo during the study.

What are the potential side effects?

While specific side effects of BIA 28-6156 aren't listed here, common clinical trial risks may include allergic reactions to components of the drug formulation, general discomforts like headaches or nausea related to medication intake.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 35 and 80 years old.

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My Parkinson's disease is in the early or mid-stage.

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I am currently receiving treatment for Parkinson's disease symptoms.

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I have a genetic variant linked to Parkinson's disease.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I did not meet the genetic screening requirements for Part A.

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I have Gaucher's disease, confirmed by symptoms or tests showing low GCase activity.

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I have a genetic mutation linked to Gaucher's disease.

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I have a genetic mutation linked to Parkinson's disease.

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I am not using strong CYP3A4 inhibitors or inducers currently.

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I have had or am planning to have advanced treatments for Parkinson's disease.

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My kidney function is reduced with an eGFR below 60 mL/min.

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I have cirrhosis or my liver tests are higher than normal.

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I am allergic or have had a reaction to BIA 28-6156.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from baseline up to week 78

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from baseline up to week 78

This trial's timeline: 3 weeks for screening, Varies for treatment, and from baseline up to week 78 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Time from baseline to clinically meaningful progression on motor aspects of experiences of daily living (assessed by MDS-UPDRS Part II score and MDS-UPDRS Part III score)

Secondary study objectives

Change from Baseline to Week 78 in the 39-Item Parkinson's Disease Questionnaire (PDQ-39) score

Change from Baseline to Week 78 in the MDS-UPDRS Total (Part I-IV) score

Change from Baseline to Week 78 in the Modified Hoehn and Yahr score

+3 more

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: BIA 28-6156 60 mgExperimental Treatment1 Intervention

Participants will be randomized to receive BIA 28-6156 60 mg during the Treatment Period.

Group II: BIA 28-6156 10 mgExperimental Treatment1 Intervention

Participants will be randomized to receive BIA 28-6156 10 mg during the Treatment Period.

Group III: PlaceboPlacebo Group1 Intervention

Placebo

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Parkinson's Disease (PD) include levodopa, dopamine agonists, MAO-B inhibitors, and amantadine. Levodopa is converted to dopamine in the brain, replenishing the diminished dopamine levels characteristic of PD. Dopamine agonists mimic dopamine by stimulating dopamine receptors. MAO-B inhibitors prevent the breakdown of dopamine, thereby increasing its availability. Amantadine helps reduce symptoms by modulating glutamate activity. These treatments are crucial as they address the core issue of dopamine deficiency, improving motor function and quality of life for PD patients. BIA 28-6156, which targets the glucocerebrosidase pathway, aims to enhance the degradation of misfolded proteins, potentially offering a disease-modifying approach by addressing underlying cellular dysfunctions.

Therapeutic innovation in Parkinson's disease: a 2020 update on disease-modifying approaches.c-Abl Inhibition Exerts Symptomatic Antiparkinsonian Effects Through a Striatal Postsynaptic Mechanism.Alterations in the nigrostriatal system following conditional inactivation of α-synuclein in neurons of adult and aging mice.