A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in Subjects With Parkinson's Disease With a Pathogenic Variant in the Glucocerebrosidase (GBA1) Gene
Overview
- Phase
- Phase 2
- Intervention
- BIA 28-6156 10 mg
- Conditions
- Parkinson's Disease
- Sponsor
- Bial R&D Investments, S.A.
- Enrollment
- 237
- Locations
- 95
- Primary Endpoint
- 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)
- Status
- Active, Not Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
The purpose of this randomized, double-blind, placebo-controlled study is to assess the efficacy of BIA 28-6156 over placebo in delaying clinical meaningful motor progression over 78 weeks in subjects with Parkinson's disease who have a pathogenic variant in the glucocerebrosidase 1 (GBA1) gene (GBA-PD).
Detailed Description
This is a 2-part (Part A \[Genetic Screening\] and Part B \[Double-Blind Treatment\]), Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics of 2 fixed dose levels of BIA 28-6156 (10 and 60 mg/day) in approximately 237 subjects with genetically confirmed GBA-PD. Part A (Genetic Screening) will identify individuals with a PD risk-associated variant in the GBA1 gene for potential enrolment into Part B (Double-Blind Treatment) of the study. Part B will consist of a screening period to ensure that all protocol inclusion/exclusion criteria for Part B of the study are met (up to 5 weeks). After screening period, eligible subjects will be randomized into 1 of 3 treatment arms (BIA 28-6156 10 mg/day, BIA 28-6156 60 mg/day, or placebo) in a 1:1:1 ratio, and enter a double-blind treatment period up to 78 weeks, followed by a 30-day (4 weeks) of safety follow-up period. Subjects must be receiving a stable dose of PD medication for at least 30 days before screening (for Part B \[Double-Blind Treatment\]) and will continue to receive their usual PD medications throughout the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects who satisfy all of the following criteria will be eligible for Part A (Genetic Screening) of the study:
- •The subject is ≥35 and ≤80 years of age at the time of informed consent.
- •The subject has a clinical diagnosis of PD for at least 1 year and for no longer than 7 years before initiation of screening (for Part A), as confirmed by a neurologist using the MDS Criteria for Parkinson's Disease.
- •The subject has a modified Hoehn and Yahr score ≤2.
- •The subject is receiving symptomatic treatment for PD.
- •The subject is capable of giving signed informed consent.
- •Subjects who satisfy all the following criteria will be eligible for Part B (Double-Blind Treatment) of the study:
- •Informed Consent - The subject is capable of giving signed informed consent.
- •The subject has a known GBA-PD risk-associated variant (as determined in Part A \[Genetic Screening\] of this study).
- •The subject has a score ≥22 on the Montreal Cognitive Assessment (MoCA) scale.
Exclusion Criteria
- •Individuals who do not satisfy the inclusion criteria for Part A (Genetic Screening) will be excluded.
- •Subjects who meet any of the following criteria for Part B (Double-Blind Treatment) are not eligible for the study.
- •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.
- •The subject is homozygous for a GBA1 pathogenic variant that is known to be associated with GD or compound heterozygous for 2 alleles that are known to be associated with GD.
- •The subject carries a known PD-associated LRRK2 pathogenic variant.
- •The subject has atypical or secondary parkinsonism by medical history or in the opinion of the investigator. Atypical parkinsonism includes, but is not limited to, diagnoses of progressive supranuclear palsy, cortico-basal syndrome, and multiple system atrophy. Secondary parkinsonism includes drug-induced, toxin-induced, postinfectious, posttraumatic, or vascular parkinsonism.
- •The subject has a history of (within 60 days before initiation of screening) or has planned upcoming major surgery that could interfere with, or for which the treatment might interfere with, the conduct of the study or that would pose an unacceptable risk to the subject in the opinion of the investigator.
- •The subject has any active or chronic disease or condition other than PD that could interfere with, or for which the treatment might interfere with, the conduct of the study or pose an unacceptable risk to the subject in the opinion of the investigator based on medical history, physical examination, vital signs, 12-lead ECG, or clinical laboratory tests. Minor deviations of laboratory values from the normal range may be acceptable if judged by the investigator to have no/minor clinical relevance.
- •The subject has a recent history (last 6 months) of abuse of addictive substances (alcohol, illegal substances), currently uses \>21 units of alcohol per week, or is a regular recreational user of sedatives, hypnotics, tranquillizers, or any other addictive agent in the opinion of the investigator.
- •The subject has a positive test for drugs of abuse at screening or before administration of the first dose of investigational medicinal product (IMP) that the investigator judges as clinically relevant. A positive test for tetrahydrocannabinol (THC) is exclusionary. A positive test for cannabinoids (not containing THC) is not exclusionary if the subject is a recreational user (not an abuser) of cannabinoids, in the opinion of the investigator, and agrees to abstain from using cannabinoids within 12 hours before study visits. A positive drug screen that is attributed to an allowed prescription drug is not exclusionary but should be agreed with the medical monitor.
Arms & Interventions
BIA 28-6156 10 mg
Participants will be randomized to receive BIA 28-6156 10 mg during the Treatment Period.
Intervention: BIA 28-6156 10 mg
BIA 28-6156 60 mg
Participants will be randomized to receive BIA 28-6156 60 mg during the Treatment Period.
Intervention: BIA 28-6156 60 mg
Placebo
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
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)
Time Frame: From Baseline up to Week 78
Time from baseline to clinically meaningful progression on motor aspects of experiences of daily living, as assessed by ≥2-point increase from baseline in Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score and no improvement in the Motor Examination, as assessed by ≥0-point increase from baseline in MDS-UPDRS Part III score. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (Range 0-52). It contains 13 questions which are to be rated by the patient and/or caregiver. Part III assesses the motor signs of PD and is rated by the investigator (Range 0-132). Part III contains 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicates more severe symptoms of PD.
Secondary Outcomes
- Time from baseline to clinically meaningful progression on motor signs of the disease (assessed by MDS-UPDRS Part III score)(From Baseline up to Week 78)
- Change from Baseline to Week 78 in the 39-Item Parkinson's Disease Questionnaire (PDQ-39) score(From Baseline up to Week 78)
- Time from baseline to any worsening on the Patient Global Impression - Change (PGI-C) scale(From Baseline up to Week 78)
- Change from Baseline to Week 78 in the MDS-UPDRS Total (Part I-IV) score(From Baseline up to Week 78)
- Change from Baseline to Week 78 in the Modified Hoehn and Yahr score(From Baseline up to Week 78)
- Time from baseline to any worsening on the Clinical Global Impression - Change (CGI-C) scale(From Baseline up to Week 78)