Ended Therapeutic exploratory (Phase II) Parkinson’s Disease

Efficacy, Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of BIA 28-6156 in GBA-PD (ACTIVATE study)

EU CTIS ID: 2022-501783-18-00

What this study is testing

To assess the efficacy of BIA 28-6156 in delaying meaningful clinical motor progression in subjects with Parkinson’s disease (PD) who have a pathogenic variant in the GBA1 gene (GBA-PD) as assessed by the Movement Disorder Society - Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part II and Part III

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Part A (Genetic Screening): The subject is ≥35 and ≤80 years of age at the time of informed consent.
6. Part B (Double-Blind Treatment): The subject is capable of giving signed informed consent, which includes understanding the purpose and risks of the study, compliance with the requirements and restrictions that are listed in the ICF and in this protocol, and authorization to use confidential health information in accordance with national and local subject privacy regulations.
7. Part B (Double-Blind Treatment): The subject has a known GBA-PD risk-associated variant (as determined in Part A [Genetic Screening] in this study). A list of permissible GBA1 mutations is presented in Appendix 4 of the study protocol.
8. Part B (Double-Blind Treatment): The subject has a score ≥22 on the MoCA scale.
9. Part B (Double-Blind Treatment): The subject does not have moderate motor complications as assessed by a score ≥3 in any of the subitems of the MDS-UPDRS Part IV.
14. Part B (Double-blind treatment): The subject does not have clinically significant psychosis in the clinical judgment of the investigator.

You likely can't join if

1. Part A (Genetic Screening): Individuals who do not satisfy the inclusion criteria for Part A (Genetic Screening; Section 5.2.1 of study protocol) will be excluded.
18. Part B (Double-Blind Treatment): The subject has renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min at screening.
19. Part B (Double-Blind Treatment): The subject has cirrhosis (Child-Pugh A, B, or C) or any of the following laboratory values at screening: serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN) or bilirubin >2 × ULN except if the subject has known or suspected Gilbert’s disease.
2. Part B (Double-Blind Treatment): The subject has 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.
20. Part B (Double-Blind Treatment): The subject has a QTcF (QT interval corrected for heart rate by Fridericia’s method) value >450 msec if male or >470 msec if female at screening.
21. Part B (Double-Blind Treatment): The subject provides a positive response on Question 4 or 5 of the C-SSRS based on the last 6 months or, in the opinion of the investigator, presents a serious risk of suicide at screening.

See the full eligibility criteria

Who can join

1. Part A (Genetic Screening): The subject is ≥35 and ≤80 years of age at the time of informed consent.
6. Part B (Double-Blind Treatment): The subject is capable of giving signed informed consent, which includes understanding the purpose and risks of the study, compliance with the requirements and restrictions that are listed in the ICF and in this protocol, and authorization to use confidential health information in accordance with national and local subject privacy regulations.
7. Part B (Double-Blind Treatment): The subject has a known GBA-PD risk-associated variant (as determined in Part A [Genetic Screening] in this study). A list of permissible GBA1 mutations is presented in Appendix 4 of the study protocol.
8. Part B (Double-Blind Treatment): The subject has a score ≥22 on the MoCA scale.
9. Part B (Double-Blind Treatment): The subject does not have moderate motor complications as assessed by a score ≥3 in any of the subitems of the MDS-UPDRS Part IV.
14. Part B (Double-blind treatment): The subject does not have clinically significant psychosis in the clinical judgment of the investigator.
10. Part B (Double-Blind Treatment): The subject has been on stable doses of PD medications (as listed in Table 6) for at least 30 days (at least 60 days for rasagiline) before initiation of screening in Part B (Double-Blind Treatment).
11. Part B (Double-Blind Treatment): The subject is able to comply with the study restrictions and is willing and able to use a Smartphone application and to wear a Smartwatch to measure PD-related motor signs for the duration of the study.
12. Part B (Double-Blind Treatment): The subject has a body mass index (BMI) of 18 to 40 kg/m2 .
13. Part B (Double-Blind Treatment): If a sexually active man or a woman of childbearing potential, the subject agrees to use highly effective birth control (Appendix 3 of the study protocol) or to remain abstinent during the trial and for 30 days after the last dose of IMP. Acceptable (highly effective) methods of contraception for this study include hormonal contraceptives (combined oral contraceptive, patch, vaginal ring, injectable, or implant); intrauterine device or system; 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).
2. Part A (Genetic Screening): 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 (Postuma, 2015).
3. Part A (Genetic Screening): The subject has a modified Hoehn and Yahr score ≤2.5.
4. Part A (Genetic Screening): The subject is receiving symptomatic treatment for PD.
5. Part A (Genetic Screening): The subject is capable of giving signed informed consent, which includes understanding the purpose and risks of the study, compliance with the requirements and restrictions that are listed in the ICF and this protocol, and authorization to use confidential health information in accordance with national and local subject privacy regulations.

What rules you out

1. Part A (Genetic Screening): Individuals who do not satisfy the inclusion criteria for Part A (Genetic Screening; Section 5.2.1 of study protocol) will be excluded.
18. Part B (Double-Blind Treatment): The subject has renal insufficiency as defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min at screening.
19. Part B (Double-Blind Treatment): The subject has cirrhosis (Child-Pugh A, B, or C) or any of the following laboratory values at screening: serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN) or bilirubin >2 × ULN except if the subject has known or suspected Gilbert’s disease.
2. Part B (Double-Blind Treatment): The subject has 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.
20. Part B (Double-Blind Treatment): The subject has a QTcF (QT interval corrected for heart rate by Fridericia’s method) value >450 msec if male or >470 msec if female at screening.
21. Part B (Double-Blind Treatment): The subject provides a positive response on Question 4 or 5 of the C-SSRS based on the last 6 months or, in the opinion of the investigator, presents a serious risk of suicide at screening.
22. Part B (Double-Blind Treatment): The subject had a positive SARS-CoV-2 test (any type) result within the 30 days before signing informed consent for Part B (Double-Blind Treatment) or has 2 or more current symptoms (e.g., sore throat, cough, fever) at the same time that are consistent with COVID-19 infection (not tested) in the opinion of the investigator.
23. Part B (Double-Blind Treatment): The subject has a clinical history that is consistent with a previous COVID-19 infection and has not recovered fully, maintaining nonspecific symptoms like, for example, fatigue, shortness of breath, difficulty concentrating, sleep disorders, fever, anxiety, and depression.
24. Part B (Double-Blind Treatment): The subject has previously received BIA 28-6156 or has a known allergy or hypersensitivity to BIA 28-6156 or any components of the formulation.
25. Part B (Double-Blind Treatment): The subject is an unsuitable candidate to receive BIA 28-6156 or is unable or unlikely to comply with the dosing schedule or study evaluations in the judgment of the investigator.
3. Part B (Double-Blind Treatment): 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 (N370S, D409H, H255Q, D140H, G202R, L324P, I260T, L444P, A190T, R120W).
10. Part B (Double-Blind Treatment): The subject is currently pregnant, is planning pregnancy within the timeframe of the study, or is breastfeeding.
4. Part B (Double-Blind Treatment): The subject carries a known PD-associated LRRK2 pathogenic variant. A list of exclusionary LRRK2 pathogenic variants is provided in Appendix 4 of the study protocol.
5. Part B (Double-Blind Treatment): 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.
6. Part B (Double-Blind Treatment): 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.
7. Part B (Double-Blind Treatment): 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.
8. Part B (Double-Blind Treatment): 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.
9. Part B (Double-blind treatment): The subject has a positive test for drugs of abuse at screening or before administration of the first dose of IMP that the investigator judges as clinically relevant. Use of cannabinoids is not exclusionary if the subject agrees to abstain from using cannabinoids within 12 hours before study visits. A positive drug screen that is attributed to an allowed prescription, including medicines containing THC, or over-the-counter (OTC) drug is not exclusionary but should be agreed with the medical monitor
26. Part B (Double-blind treatment): The subject is a member of a protected/vulnerable population, defined as persons who are pregnant, parturient, or breastfeeding; minors; persons who are deprived of liberty; persons who are under psychiatric hospital care; persons who are admitted to a health or social institution for purposes other than research; adults who are under legal protection or who are unable to express their consent; persons who are in an emergency situation and are unable to express their prior consent; and persons are who are non-affiliated or a non-beneficiary of a social security system [This does not apply to persons in the United States without health insurance].
27. Part B (Double-blind treatment): The subject is a relative of the investigator or sponsor or the relative of an employee of the sponsor
11. Part B (Double-Blind Treatment): The subject is using a strong CYP3A4 modulator at the time of screening for Part B (Double-Blind Treatment). CYP3A4 strong inhibitors and inducers include, but are not limited to, the medications that are listed in Appendix 4 of the study protocol.
12. 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 BCRP substrate medications that are considered exclusionary (based on concomitant use with BCRP inhibitors, as provided in the Summary of Product Characteristics [SmPC], for the medication) are included, but are not limited to, the medications that are listed in Appendix 4 of the study protocol.
13. 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, quetiapine, risperidone, and aripiprazole); metoclopramide; prochlorperazine; methyldopa; tetrabenazine; deutetrabenazine; valbenazine; or reserpine or a prior history or continuation or initiation during the study of ambroxol at doses >120 mg/day.
14. Part B (Double-Blind Treatment): The subject has received a vaccination within 14 days before administration of the first dose of IMP.
15. Part B (Double-Blind Treatment): The subject has a prior history of or there is a plan to conduct 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.
16. Part B (Double-Blind Treatment): 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.
17. Part B (Double-Blind Treatment): The subject has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), or human immunodeficiency virus 1 (HIV-1) or 2 (HIV-2) at screening. If reflex testing for hepatitis B or HCV DNA is negative, the subject may be eligible for the study.

The study team makes the final eligibility decision.

Where it's taking place

Canada
United Kingdom
United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Canada; United Kingdom; United States. Enter your location above to see the nearest site and check your eligibility.

Explore other conditions

Obesity Type 2 diabetes Type 1 diabetes Prediabetes Weight loss Metabolic syndrome High cholesterol High triglycerides High blood pressure PCOS Hypothyroidism Thyroid disease Gout Fatty liver disease (NAFLD/NASH)Heart failure Coronary artery disease

BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.