A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS PRASINEZUMAB IN PARTICIPANTS WITH EARLY-STAGE PARKINSON’S DISEASE
Topic / Pathology
- Parkinson's Disease
Objectives
Primary objective: To evaluate the efficacy of prasinezumab compared with placebo (in participants on stable symptomatic monotherapy with levodopa, irrespective of their increase in LEDD during the study, and study treatment discontinuation).
Secondary Objectives :
1) To evaluate the efficacy of prasinezumab compared with placebo (in participants on stable symptomatic monotherapy with levodopa, irrespective of their increase in LEDD during the study, and study treatment discontinuation).
2) To evaluate the efficacy of prasinezumab compared with placebo (in participants on stable symptomatic monotherapy with levodopa, irrespective of their increase in LEDD during the study, and study treatment discontinuation).
3) To evaluate the safety of prasinezumab compared with placebo (in participants on stable symptomatic monotherapy with levodopa, irrespective of their increase in LEDD during the study, and study treatment discontinuation)
4) To further characterize PK of prasinezumab
5) To further evaluate the immunogenicity of prasinezumab
Sponsor
F. Hoffmann-La Roche Ltd
Investigator
Jean Christophe Corvol
Critères d'inclusion
• Signed Informed Consent Form
• Ability and willingness to comply with all aspects of the protocol including completion of procedures, interviews, questionnaires, assessments, for the duration of the study
• Age ≥ 50 to 85 years at the time of signing Informed Consent Form
• Body weight within 40−110 kg (88−242 lbs) and a body mass index within the range 18−34 kg/m2
• Diagnosis of idiopathic PD based on Movement Disorder Society (MDS) criteria (Postuma et al. 2015) with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), without any other known or suspected cause of parkinsonism
• Has received monotherapy treatment with up to 450 mg levodopa per day with stable doses for at least 3 months prior to baseline and is considered optimally managed on this regimen by the investigator at the time of randomization – ′Monotherapy treatment′ implies that the participant has been treated with the same unique treatment (levodopa only) for at least 3 months prior to baseline – ′Stable doses′ for at least 3 months prior to baseline imply that the daily dose and the daily frequency of dosing was stable for at least 3 months prior to baseline – For participants on carbidopa and levodopa extended-release capsules (Crexont, Rytary), the equivalent dose of immediate release levodopa needs to be calculated, and this value needs to be ≤ 450 mg/day, with stable doses for at least 3 months prior to baseline
• No anticipated changes in PD medication from baseline throughout the study duration based on clinical status during screening and prior to randomization • A diagnosis of PD for at least 3 months to a maximum of 3 years at screening
• An MDS-UPDRS Part IV score of 0 at screening and prior to randomization • H&Y Stage 1 or 2 off medication at screening and prior to randomization • Fluency in the language of the outcome measures at the site
• No acute or chronic infectious hepatitis B virus (HBV; [i.e., hepatitis B surface antigen (HBsAg positive test)]), for hepatitis C virus (HCV), or HIV 1 or 2. Successfully treated patients with HCV (undetectable HCV RNA) are eligible for enrollment. Participants who are immune due to HBV natural infection or HBV vaccination are eligible. o Negative HBsAg test at screening o Positive hepatitis B core antibody (HBsAb) test at screening or a negative HBsAb at screening accompanied by either of the following: – Negative hepatitis B core antibody (HBcAb) – A Positive HBcAb test followed by a negative (per local laboratory definition) HBV DNA test The HBV DNA test must be performed for individuals who have a negative HBsAg test, a negative HBsAb test, and a positive HBcAb test. o Negative HCV antibody test at screening or a positive HCV antibody test followed by a negative HCV RNA test at screening The HCV RNA test must be performed for individuals who have a positive HCV antibody test. o Negative HIV – 1 and HIV - 2 antibody test at screening
• Agreement to adhere to the contraception requirements
Critères de non-inclusion
• Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required (Section 5.5.2) Participants of childbearing potential must have a negative serum pregnancy test result during screening prior to initiation of study treatment
• Medical history indicating a parkinsonian syndrome other than idiopathic PD, including but not limited to progressive supranuclear palsy, multiple system atrophy, drug-induced parkinsonism, vascular parkinsonism, primary dystonia
• Known carriers of PD gene mutations (PRKN, PINK1, or DJ1) – Note: Carriers of GBA, synuclein, or LRRK2 mutations are allowed
• History of MDS-UPDRS Part IV > 0 and/or of PD-related motor complications (e.g., dyskinesias and motor fluctuations)
• History of PD-related freezing episodes or falls
• History of brain surgery for PD or intention to perform brain surgery for PD for the duration of the double-blind treatment period of the trial • Diagnosis of PD dementia
• Diagnosis of a significant neurologic disease other than PD (including but not limited to Huntington’s disease, normal pressure hydrocephalus, cerebrovascular disease including stroke, frontotemporal dementia, Alzheimer’s disease, dementia with Lewy bodies, multiple sclerosis, brain tumor); history of repeated head injury; history of epilepsy or seizure disorder other than febrile seizures as a child
• History of a condition that could interfere with the assessment of the motor aspects of the disease, e.g., chronic pain • History of, or screening brain MRI scan indicative of, clinically significant abnormality including but not limited to prior hemorrhage or infarct > 1 cm3 or > 3 lacunar infarcts • History of clinically significant psychiatric symptoms (e.g., confusion, hallucination, delusion, excitation, delirium, abnormal behavior) or any clinically significant psychiatric disease other than mild depression or depressive mood, or mild anxiety arising in the context of PD
• 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
• Within the last year, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction) – Heart failure classified as New York Heart Association Class I or II cardiac disease is allowed if not associated with hospitalization within the previous 12 months
• Chronic uncontrolled hypertension (e.g., systolic blood pressure/diastolic blood pressure readings generally > 165/ > 100 mmHg • Currently active infection or serious infection (e.g., pneumonia, septicemia) within 8 weeks before baseline, as determined by the Investigator
• Drug and/or alcohol abuse within 12 months prior to screening, and/or expected anytime during the study, in the investigator's judgment – Abuse is defined as a maladaptive pattern of use that leads to failure to fulfill major work or social obligations or use in situations where it leads to physical danger or legal problems and may be the focus of clinical attention – Nicotine is allowed – Marijuana is not allowed (this includes all forms of cannabidiol and tetrahydrocannabinol), even if given for therapeutic use. Participants with a positive urine drug screen are not eligible
• Clinically significant abnormalities in laboratory test results at the screening visit, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis, including: – Total bilirubin, ALT or AST > 2x the upper limit of normal (ULN) – Serum creatinine > 1.5x the ULN – Hematocrit less than 35% for males and less than 32% for females, or ANC count of < 1500/µL (with the exception of a documented history of a chronic benign neutropenia), or platelet cell count of < 120,000/ µL; INR > 1.4 (in patients not treated with anticoagulants) or other coagulopathy – A positive urine drug screen for a drug of abuse as outlined in the central laboratory manual Investigators should use their best clinical judgment in cases where results may be erroneous (e.g., permitted use of benzodiazepines, ingestion of food/food supplements, etc.)
• Concomitant disease or unstable medical condition within 6 months of screening, or as specified below, that could interfere with, or treatment that might 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
• Autoimmune disease However, well controlled conditions such as quiescent rheumatoid arthritis, controlled type I diabetes, or mild-to-moderate psoriasis are acceptable
• Any previous administration of prasinezumab or other compound targeting aSyn
• Enrollment in another investigational study
Status
Recruiting
