Prevent Cognitive Decline in GBA-associated Parkinson's Disease

NCT07055087 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: PreCoDe2024-513496-40-00
• Study Type: interventional
• Target: 120
• Locations: 7 countries
• Sites: 8

Brief Summary

This is a proof-of-concept trial to investigate the efficacy of prasinezumab to slow or prevent cognitive decline in people with Parkinson's disease carrying a severe mutation in the GBA (glucocerebrosidase) gene. The duration of the intervention per patient will be 104 weeks with monthly infusions. The investigators plan to enroll 120 participants (60 participants per treatment arm). This study will be conducted across Europe in the following countries: France, Germany, Italy, Luxembourg, Spain, Sweden, UK.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Cognitive function; GBA; anti-α-synuclein; monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• Parkinson's Disease Cognitive Composite Score (PDCCS)

  To assess the efficacy of prasinezumab compared with placebo on cognitive function at week 104 measured by the Parkinson's Disease Cognitive Composite Score (PDCCS). Composite score that includes the following cognitive tests: * LNS (Attention) * Derived-Sem. Fluency-Animal T-Score (Executive function) * Derived-Delayed Recall T-Score (Memory) * MoCA (Global cognition) Per single Test: Group Mean and Standard Deviation (SD) at Baseline = reference ZBaseline = (xBaseline - Group MeanBaseline) / SDBaseline ZFollow-up = (xFollow-up - Group MeanBaseline) / SDBaseline Mean of Z-Scores of relevant Tests per Patient per Visit Min-Max: n.a. (higher values mean a better outcome)

  week 104

Secondary Outcomes (16)

• Cognitive function (MoCA_z)

  week 104

• PD-MCI

  week 104

• PDD

  week 104

• MDS-UPDRS I-IV

  week 104

• Levodopa-equivalent dosage

  week 104

Other Outcomes (27)

• Exploratory: cognitive function (MoCA_z)

  week 104

• Exploratory: Cognitive function (MoCA ≥ 26)

  week 104

• Exploratory: Cognitive function (PD-MCI)

  week 104

Study Arms (2)

Prasinezumab

EXPERIMENTAL

prasinezumab 1500 mg monthly infusion

Drug: Prasinezumab

Sodium chloride 0,9% infusion

PLACEBO COMPARATOR

saline infusion (0,9 % sodium chloride) monthly infusion

Drug: Sodium Chloride

Interventions

Prasinezumab DRUG

Prasinezumab 1500 mg monthly infusion

Prasinezumab

Sodium Chloride DRUG

Saline infusion (0,9 % sodium chloride) monthly infusion

Sodium chloride 0,9% infusion

Eligibility Criteria

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

You may qualify if:

• Diagnosis of PD according to MDS-Criteria.
• Known heterozygous severe GBA mutation (based on PD-related pathogenicity).
• MoCA ≥ 21.
• HY in dopaminergic ON ≤3.
• to 80 years of age at the time of signing the Informed Consent.
• Able and willing to provide written informed consent and to comply with the study protocol according to the International Council for Harmonization (ICH) and local regulations.

You may not qualify if:

• Current or Past Medical History:
• Known pathogenic mutation carriers of the following familial PD genes: PRKN, PINK1, DJ1, LRRK2.
• Medical history indicating a Parkinsonian syndrome other than sporadic PD (progressive supranuclear palsy, multiple system atrophy, drug-induced parkinsonism, essential tremor, primary dystonia).
• A diagnosis of a significant CNS disease other than PD.
• Previous, current or planned (within next 2 years) treatment with Deep Brain Stimulation (DBS) or ablation with high-intensity focused ultrasound or planned treatment with these within the next 2 years.
• History of brain MRI scan indicative of clinically significant abnormality of prior hemorrhage or ischemic infarction \> 1 cm3, \> 3 lacunar infarctions, vascular encephalopathy with white matter lesions according to Fazekas grade III. Clinical routine brain MRI scan must be available within 2 years before Screening.
• Concomitant disease or condition, or treatment thereof that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study or interfere with the participant's ability to comply with study procedures or abide by study restrictions, or with the ability to interpret safety data, including:
• Autoimmune disease (however, well controlled conditions such as quiescent rheumatoid arthritis \[RAS\], controlled type I diabetes, or mild-to-moderate psoriasis not requiring systemic medications may be acceptable after discussion with Sponsor).
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, non-metastatic prostate cancer, or Stage I uterine cancer.
• Any active infectious disease at Screening.
• Current, or history of, alcohol or drug abuse or other dependence (except nicotine dependence) within one year before Screening. Drug and/or alcohol abuse within 12 months prior to screening, in the investigator's judgment (except nicotine dependence, Marijuana use is not allowed \[this includes all forms of cannabidiol and tetrahydrocannabinol even if given for therapeutic use\]).
• Any febrile illness within one week prior to first dose administration.
• Any current psychiatric diagnosis according to Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5), International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) or equivalent, that may interfere with the participant's ability to perform the study and all assessments (e.g., major depression (BDI-II \>28, mental retardation, schizophrenia, bipolar disorder, etc.).
• Acute suicidality, as evidenced by a) Question 5 ("Lifetime"/"Since last visit") on the Columbia- Suicide Severity Rating Scale (C-SSRS), indicating active suicidal ideation with any intent to act, at Screening or baseline (Day 1), or answering "yes" for Question 3 ("In the Past Month"/"Since last visit") on the C-SSRS, indicating active suicidal ideation with any methods (not plan) without intent to act, at Screening or baseline (Day 1)
• The following cardiovascular conditions:

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (8)

Sorbonne University, Pitié-Salpêtrière Hospital

Paris, France

Location

University Hospital Tubingen

Tübingen, Germany

Location

University of Brescia and ASST Spedali Civili of Brescia

Brescia, Italy

Location

Fondazione IRCCS Ca' Granda Policlinico Hospital

Milan, Italy

Location

University of Luxemburg

Luxembourg, Luxembourg

Location

Hospital Universitario HM Puerta del Sur, Madrid

Madrid, Spain

Location

Karolinska University of Stockholm

Stockholm, Sweden

Location

University of Oxford

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Sodium Chloride

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Kathrin Brockmann, Prof. Dr.

  University Hospital Tuebingen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kathrin Brockmann, Prof. Dr.

CONTACT

+49 7071 29 80438; kathrin.brockmann@uni-tuebingen.de

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: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2025
• First Posted: July 8, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): May 1, 2031
• Last Updated: July 8, 2025

Record last verified: 2025-05

Locations

DE (1); IT (2); ES (1); GB (1); FR (1); SE (1); LU (1)