Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD

NCT05819359 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: BIA 28-6156-2012022-501783-18-00
• Study Type: interventional
• Target: 237
• Locations: 11 countries
• Sites: 95

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).

Conditions

Parkinson's Disease

Keywords

Parkinson Disease; Neurodegenerative Diseases; Central Nervous System Diseases; Glucocerebrosidase (GCase) activity; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; GBA1 gene; BIA 28-6156; Phase 2

Outcome Measures

Primary Outcomes (1)

• 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 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.

  From Baseline up to Week 78

Secondary Outcomes (6)

• 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

• Time from baseline to any worsening on the Clinical Global Impression - Change (CGI-C) scale

  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

Study Arms (3)

BIA 28-6156 10 mg

EXPERIMENTAL

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

Drug: BIA 28-6156 10 mg

BIA 28-6156 60 mg

EXPERIMENTAL

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

Drug: BIA 28-6156 60 mg

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

BIA 28-6156 10 mg DRUG

BIA 28-6156 10 mg, once daily, oral administration.

BIA 28-6156 10 mg

BIA 28-6156 60 mg DRUG

BIA 28-6156 60 mg, once daily, oral administration.

BIA 28-6156 60 mg

Placebo DRUG

Placebo, once daily, oral administration.

Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤2.5.
• 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.
• The subject does not have severe motor fluctuations or disabling dyskinesias in the clinical judgment of the investigator.
• The subject has been on stable doses of PD medications for at least 30 days (at least 60 days for rasagiline) before initiation of screening in Part B (Double-Blind Treatment).
• The subject is able to comply with the study restrictions.
• The subject has a body mass index (BMI) of 18 to 40 kg/m2.
• If a sexually active man or a women of childbearing potential, the subject agrees to use highly effective birth control or to remain abstinent during the trial and for 30 days after the last dose of IMP. Complete abstinence from sexual intercourse if this is the subject's usual and preferred lifestyle; or sexual partner with surgical sterilization (e.g., tubal ligation, hysterectomy and/or bilateral oophorectomy, vasectomy).

You may not qualify if:

• 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 is currently pregnant, is planning pregnancy within the timeframe of the study, or is breastfeeding.
• The subject is using a strong inhibitors and inducers CYP3A4 at the time of screening for Part B (Double-Blind Treatment).
• The subject is using a breast cancer resistance protein (BCRP) substrate (e.g., pravastatin, rosuvastatin, glyburide) at the time of screening for Part B (Double-Blind Treatment).
• The subject has used any of the following medications within 60 days before Baseline: typical or atypical antipsychotics (including, but not limited to, clozapine, pimavanserin, olanzapine, risperidone, and aripiprazole), metoclopramide, prochlorperazine, methyldopa, tetrabenazine, deutetrabenazine, valbenazine, or reserpine.
• The subject has received a vaccination within 14 days before administration of the first dose of IMP.
• The subject has a prior history of or there is a plan to conduct deep brain stimulation (DBS), lesional procedures, (i.e., thalamotomy), or focused ultrasound; to initiate gene therapy treatment for PD; or to initiate use of any formulation of intestinal infusion or continuous subcutaneous infusion of PD medications.
• The subject is currently participating in or has participated in an investigational drug study within 3 months or 5 half-lives, whichever is longer; in a therapeutic device study within 3 months before the first dose of IMP; or has previously participated in a gene therapy trial. Concurrent participation in an observational study is acceptable.

Sponsors & Collaborators

• Bial R&D Investments, S.A.: lead

Study Sites (95)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

University of California San Diego

La Jolla, California, 92037, United States

Location

Cedars-Sinai

Los Angeles, California, 90048, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Parkinson's Center and Movement Disorders of Boca Raton

Boca Raton, Florida, 33486, United States

Location

University of Miami, Dept. of Neurology

Miami, Florida, 33136, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Morehouse School of Medicine

Atlanta, Georgia, 30310, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Baylor University Medical Center

Baltimore, Maryland, 21287, United States

Location

The Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Quest Research Institute, LLC

Farmington Hills, Michigan, 48334, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Struthers Parkinson's Center- East

Saint Paul, Minnesota, 55130, United States

Location

Park Nicollet Struther's Parkinson's Center (Struthers Parkinsons Center at HealthPartners)

Saint Paul, Minnesota, 55427, United States

Location

Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08901, United States

Location

Icahn School of Medicine at Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Weil Cornell Medical Center

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Northwell Health Physician Partners

New York, New York, 10075-1851, United States

Location

Northwell Health

New York, New York, 10075, United States

Location

University of Rochester Neurology

Rochester, New York, 14642, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University Hospitals Cleveland Medical Center

South Euclid, Ohio, 44121, United States

Location

Univerity of Toledo

Toledo, Ohio, 43614, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Parkinson's Disease and Movement Disorders Cente at University of Pennyslvania

Philadelphia, Pennsylvania, 19107, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MUSC

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center - San Antonio

San Antonio, Texas, 78229, United States

Location

Intermountain Healthcare

Salt Lake City, Utah, 84107, United States

Location

Evergreen Neuroscience Institute

Kirkland, Washington, 98034, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Inland Northwest Research

Spokane, Washington, 99202, United States

Location

Clinique Neuro-Outaouais (Neuro-Outaouais Clinic)

Gatineau, Quebec, Canada

Location

Montreal Neurological Institute & Hospital

Montreal, Quebec, 3801, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Canada

Location

CHU de Nantes - Hopital Nord Laennec

Nantes, France

Location

CHU de Nice Hopital Pasteur

Nice, 6002, France

Location

CHU de Nimes

Nîmes, France

Location

Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Pitie-Salpetriere - Centres d'Investigation Clinique (CIC) Paris-Est

Paris, France

Location

CHU de Rennes Hopital Pontchaillou

Rennes, France

Location

CIC Toulouse

Toulouse, France

Location

Hopital Paule de Viguier

Toulouse, France

Location

Neurologisches Fachkrankenhaus für, Bewegungsstörungen und Parkinson

Beelitz-Heilstätten, 14547, Germany

Location

Gertrudis Clinic Biskirchen, Parkinson-Center

Biskirchen, 35638, Germany

Location

Paracelsus-Elena-Klinik

Kassel, 34128, Germany

Location

Universitats klinikum Marburg

Marburg, 35039, Germany

Location

Klinikum der Universität München, Campus Grosshadern, Neurologische Klinik und Poliklinik

Munich, 81377, Germany

Location

Ludwig-Maximilians University Munich

Munich, Germany

Location

Parkinson-Klinik Ortenau GmbH&Co KG

Wolfach, 77709, Germany

Location

IRCCS Istituto Delle Scienze Neurologiche DI

Bologna, Italy

Location

Spedali Civilia di Brescia

Brescia, 25123, Italy

Location

Ospedale Antonio Perrino

Brindisi, 72100, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

IRCCS Carlo Besta Neurological Institute

Milan, 20133, Italy

Location

Universita degli Studi della Campania Luigi Vanvitelli - Clinica Neurologia I

Naples, 80138, Italy

Location

Universita degli Studi di Padova - Azienda Ospedaliera di Padova - Clinica Neurologica

Padova, 35128, Italy

Location

IRCSS San Raffaele Pisana

Roma, 163, Italy

Location

Istituto Clinico Humanitas

Rozzano, 20086, Italy

Location

A.O.U. San Giovanni di Dio Ruggi d'Aragona Centro Parkinson- Piano Rialzato Corpo QT

Salerno, 84125, Italy

Location

Amsterdam Medical Center UMC

Amsterdam, Netherlands

Location

University Medical Center Groningen

Groningen, Netherlands

Location

St. Antonius Ziekenhuis (St. Antonius Hospital) - Utrecht

Utrecht, Netherlands

Location

Centrum Medyczne NEUROMED Sp. z o.o. ul.

Bydgoszcz, 85-163, Poland

Location

Krakowkska Akademia Neurologii Sp. z o.o

Krakow, 31-505, Poland

Location

NeuroKlinika Gabinet Lekarski

Lodz, 90-640, Poland

Location

Centro Hospitalar Universitario de Coimbra

Coimbra, Portugal

Location

Hospital Senhora da Oliveira de Guimaraes

Guimarães, 4835-044, Portugal

Location

Centro Hospitalar Universitario de Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital S.JOÃO

Porto, 4200-319, Portugal

Location

CNS - Campus Neurologico

Torres Vedras, Portugal

Location

Hospital Universitari Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Hospital Vall D´Hebron

Barcelona, 08035, Spain

Location

Hospital Universitaio de La Princesa

Madrid, 28006, Spain

Location

Hospital Ruber Internacional

Madrid, 28034, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Skane University Hospital, Lund University

Lund, 221 85, Sweden

Location

Neurologmottagningen, QD 62

Uppsala, Sweden

Location

NHS Tayside-Ninewells Hospital and Medical School

Dundee, United Kingdom

Location

Glasgow Memory Clinic

Glasgow, United Kingdom

Location

King's College London - David Goldberg Centre

London, United Kingdom

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital

Newcastle upon Tyne, United Kingdom

Location

University Hospitals Plymouth NHS Trust

Plymouth, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease; Neurodegenerative Diseases; Central Nervous System Diseases; Motor Activity; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders

Condition Hierarchy (Ancestors)

Brain Diseases; Nervous System Diseases; Synucleinopathies; Behavior

Study Officials

• Raquel Costa

  Bial R&D Investments, S.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2023
• First Posted: April 19, 2023
• Study Start: March 31, 2023
• Primary Completion: April 2, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: May 13, 2026

Record last verified: 2026-05

Locations

PT (5); IT (10); CA (3); NL (3); SE (2); PL (3); FR (7); ES (7); GB (5); US (43); DE (7)