A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants with Early Parkinson's Disease

• Register: EUCTR
• Last refreshed on: 7 October 2024
• Main ID: EUCTR2020-004997-23-FR
• Date of registration: 02/03/2021
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants with Early Parkinson's Disease
• Scientific title: A PHASE IIB, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS PRASINEZUMAB IN PARTICIPANTS WITH EARLY PARKINSON'S DISEASE
• Date of first enrolment: 11/05/2021
• Target sample size: 575
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004997-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Canada, France, Italy, Luxembourg, Poland, Spain, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
• Age >=50-85 years at time of signing the Informed Consent Form
• Diagnosis of idiopathic Parkinson's disease (PD) based on Movement disorder society (MDS) criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), without any other known or suspected cause of parkinsonism
• On symptomatic PD medication for at least 6 months, with stable doses for 3 months prior to baseline
• A diagnosis of PD for at least 6 months to maximum 3 years at screening
• Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV score= 0
• Hoehn and Yahr (H&Y) Stage I or II in ON and OFF states
• Dopamine transporter imaging with single photon emission computed tomography (DaT-SPECT) imaging consistent with dopamine transporter deficit, as assessed by the central reader
• No anticipated changes in PD medication from baseline throughout the study duration based on clinical status during screening
• Willingness and ability to use a smartphone application to measure PD-related symptoms for the duration of the study
• Willingness and ability to wear a smartwatch to measure PD-related motor signs

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 259
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 316

Exclusion criteria:
• Medical history indicating a Parkinsonian syndrome other than idiopathic PD
• Diagnosis of PD dementia
• Diagnosis of a significant central nervous system (CNS) disease other than Parkinson’s disease
• Within the last year, unstable or clinically significant cardiovascular disease
• Uncontrolled hypertension
• Drug and/or alcohol abuse within 12 months prior to screening, in the investigator's judgment (Nicotine is allowed, Marijuana use is not allowed)
• Clinically significant abnormalities in laboratory test results at the screening visit, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis
• Allergy to any of the components of prasinezumab, a known hypersensitivity, or a previous IRR following administration of any other monoclonal antibody
• Any contraindications to obtaining a brain MRI
• Any contraindications to DaT-SPECT imaging


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Early Parkinson's disease
MedDRA version: 20.0 Level: PT Classification code 10061536 Term: Parkinson's disease System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: aSyn Mab
Product Code: RO7046015
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Prasinezumab
Current Sponsor code: RO7046015
Other descriptive name: PRX002, ELT2, anti-alpha-synuclein monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 180-
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use
Pharmaceutical form of the placebo: Solution for injection/infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: • To evaluate the efficacy of prasinezumab compared with placebo on basis of time-to-worsening of patient’s motor function as reported by the patient and confirmed by the clinician, time to meaningful worsening in the overall disease as reported by the patient and by the clinician, change from baseline in motor function, change from baseline in bradykinesia and change from baseline in motor aspects of experiences of daily living
• To evaluate the safety of prasinezumab compared with placebo
• To characterize the prasinezumab pharmacokinetic (PK) profile
• To evaluate the immune response to prasinezumab

Primary end point(s): Time to meaningful progression on motor signs of the disease, as assessed by >5 points increase in MDS-UPDRS Part III score from baseline

Main Objective: To evaluate the efficacy of prasinezumab compared with placebo on basis of time to meaningful progression on motor signs of the disease

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Outcome(s)

Secondary end point(s): 1. Time-to-worsening of patient’s motor function as reported by the patient in MDS-UPDRS Part II and confirmed by the clinician in MDS-UPDRS Part III
2. Time to meaningful worsening in Patient Global Impression of Change (PGI-C, Overall Disease Subscale)
3. Time to meaningful worsening in Clinician Global Impression of Change (CGI-C, Overall Disease Subscale)
4. Change in motor function from baseline to Week 76, as measured by the MDS-UPDRS Part III total score
5. Change in bradykinesia from baseline to Week 76, as measured by the MDS-UPDRS Part III bradykinesia subscore
6. Change in motor aspects of experiences of daily living from baseline to Week 76, as measured by MDS-UPDRS Part II
7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
8. Incidence of adverse events of special interest
9. Incidence of treatment discontinuation due to adverse events
10. Incidence and severity of infusion-related reactions (IRRs)
11. Change from baseline in vital signs
12. Incidence of abnormal vital sign measurements
13. Change from baseline in electrocardiogram (ECG) assessments
14. Incidence of abnormal ECG assessments
15. Change from baseline in laboratory measurements
16. Incidence of abnormal laboratory measurements
17. Incidence of physical and neurologic examination abnormalities
18. Change from baseline in suicidal ideation, as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
19. Serum concentration of prasinezumab at specified timepoints
20. Prevalence of anti-drug antibodies (ADAs) against prasinezumab at baseline
21. Incidence of ADAs against prasinezumab during the study

Timepoint(s) of evaluation of this end point: 1-3. Throughout the study
4-6. Baseline (Day 0) to 76 weeks
7-10. Up to end of study visit
11. Baseline to end of study visit
12. Up to end of study visit
13. Baseline to end of study visit
14. Up to end of study visit
15. Baseline to end of study visit
16-17. Up to end of study visit
18. Baseline end of study visit
19. At weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76 and after week 76 every 12 weeks until the end of the study. 20. At Baseline
21. Up to end of study visit

Secondary ID(s)

BN42358

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 09/04/2021
Contact: