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

Phase 2Active Not RecruitingNCT04777331

Hoffmann-La Roche586 enrolled

Overview

This is a multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy and safety of intravenous (IV) prasinezumab versus placebo in participants with Early Parkinson's Disease (PD) who are on stable symptomatic PD medication.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

586

Conditions

Parkinsons Disease

Interventions

PrasinezumabDRUG

Prasinezumab will be administered as an IV infusion to participants Q4W.

PlaceboDRUG

Prasinezumab placebo will be administered to participants.

Eligibility

Sex: ALLMin age: 50 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of idiopathic PD based on 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, with stable doses for at least 3 months prior to baseline * A diagnosis of PD for at least 3 months to maximum 3 years at screening * MDS-UPDRS Part IV score of 0 at screening and prior to randomization * Hoehn and Yahr (H\&Y) Stage I or II in OFF medication state at screening and prior to randomization * 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 Exclusion Criteria: * Medical history indicating a Parkinsonian syndrome other than idiopathic PD * Diagnosis of PD dementia * Diagnosis of a significant neurologic disease other than PD * 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 magnetic resonance imaging (MRI) * Any contraindications to DaT-SPECT imaging

Locations (110)

Outcomes

Primary Outcomes

DBT Period: Time to Confirmed Motor Progression Event Assessed by Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III

Time to confirmed motor progression event was the first time point of a worsening event defined as either \>= 5 points increase in MDS-UPDRS Part III score (assessed in "OFF" medication state) from baseline sustained over 2 consecutive assessments or a change in medication after first occurrence of \>= 5 points increase in MDS-UPDRS Part III score from baseline \& before follow-up assessment. MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment.

Time frame: From study start to end of DBT period to at least 76 weeks

Secondary Outcomes

DBT Period: Time-to-worsening of Participant's Motor Function as Reported by the Participant in the Presence of a Confirmed Motor Progression Event

Time to worsening of the motor function was defined as ≥3 points increase in MDS-UPDRS Part II score from baseline in the presence of a confirmed motor progression event. For the confirmed motor progression event the definition is as per primary endpoint definition. MDS-UPDRS Part II assesses motor experiences of daily living \& contained 13 questions answered by participant. For each question a numeric score is assigned between 0-4, 0 = Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Score range: 0 to 52 with higher score=severe impairment.

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Time to Meaningful Worsening in Participant Global Impression of Change (PGI-C) Overall Disease Subscale

The PGI is a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (PGI-C) was intended to measure health state changes as reported by the participant on a 7-point scale (1=Very much improved to 7=Very much worse). The meaningfulness of the change was assessed and reported by the participant.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of Alabama at Birmingham

Birmingham, Alabama, United States

Barrow Neurological Institute

Phoenix, Arizona, United States

Neurology Center of North Orange County

Fullerton, California, United States

UC San Diego

La Jolla, California, United States

Keck School of Medicine of USC

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, United States

Institute for Neurodegenerative Disorders

New Haven, Connecticut, United States

JEM Research LLC

Atlantis, Florida, United States

...and 100 more locations

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Time to Meaningful Worsening in Clinician Global Impression of Change (CGI-C) Overall Disease Subscale

The CGI was a measure commonly used in PD clinical trials to provide a concise assessment of overall health state. The change component (CGI-C) was intended to measure health state changes as reported by the clinician on a 7-point scale (1=Very much improved to 7=Very much worse).

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Time to Onset of Motor Complications as Assessed Through MDS-UPDRS Part IV

MDS-UPDRS Part IV assessed motor complications of symptomatic treatment, dyskinesias, and motor fluctuations. The rater completed this assessment only for participants on L-Dopa treatment.

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Change in Motor Function From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Score

MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. The total MDS-UPDRS Part III score (ranging from 0 to 132) is calculated by summing these 33 individual ratings, with higher scores indicating severe impairment.

Time frame: From baseline up to Week 76

DBT Period: Change in Bradykinesia and Rigidity From Baseline to Week 76, as Measured by the MDS-UPDRS Part III Bradykinesia and Rigidity Subscore

MDS-UPDRS Part III is a clinician rater scale that assessed the motor signs of PD. The scale is composed of 18 clinical domains or tasks, which yield 33 distinct scores or ratings. For each distinct rating, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, and 4 = Severe. For bradykinesia, subscore ranges from 0 to 52, while rigidity subscore ranges from 0 to 20, with higher scores indicating greater impairment. Change in bradykinesia and rigidity was assessed in "OFF" medication state. Adjusted mean is reported here.

Time frame: From baseline up to Week 76

DBT Period: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any significant hazard, contraindication, or side effect that is fatal or life-threatening, requires hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention. Number of participants with atleast 1 AE and SAE are reported here.

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Number of Participants With Adverse Events of Special Interest (AESI)

An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated alanine transaminase (ALT) \& aspartate aminotransferase (AST) in combination with either an elevated bilirubin/clinical jaundice defined by Hy's law and suspected transmission of an infectious agent by study drug.

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Number of Participants With Treatment Discontinuation Due to AEs

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Number of Participants With Infusion Related Reactions (IRRs)

IRRs were defined as any signs and symptoms (AEs) occurring during infusion and/or within 24 hours administration after the end of infusion and were considered related to study treatment by the investigator. Symptoms include flushing, rash, respiratory difficulty, hypotension, tachycardia.

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Number of Participants With in Suicidal Ideation, as Measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)

C-SSRS=assessment tool used to assess lifetime suicidality of participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, and attempts with actual/potential lethality. Categories have binary responses (yes/no) and include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.

Time frame: From study start to end of DBT period to at least 76 weeks

DBT Period: Maximum Observed Concentration at Steady-state (Cmax,SS)

Time frame: Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76

DBT Period: Minimum Observed Concentration at Steady-state (Cmin,SS)

Time frame: Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76

DBT Period: Area Under the Serum Concentration Time Curve Over the Dosing Interval (AUCTau,SS)

Time frame: Day 1 of Weeks 1, 2, 4, 8, 12, 24, 36, 52, 64, 76

DBT Period: Percentage of Participants With Anti-Drug Antibodies (ADAs) at Baseline and Post-Treatment

Time frame: From study start to end of DBT period to at least 76 weeks

OLE Period: Number of Participants With AEs and SAEs

Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)

OLE Period: Number of Participants With AESI

An AE was any untoward medical occurrence in participant administered a pharmaceutical product \& which does not necessarily have to have a causal relationship with treatment. It can therefore be any unfavorable and unintended sign (including abnormal laboratory values/ abnormal clinical test results), symptoms/disease temporally associated with use of pharmaceutical product, whether/not considered related to product. AESIs included potential drug-induced liver injury that include an elevated ALT \& AST in combination with either an elevated bilirubin/clinical jaundice defined by Hy's law and suspected transmission of an infectious agent by study drug.

Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)

OLE Period: Number of Participants With IRRs

Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)

OLE Period: Number of Participants With in Suicidal Ideation, as Measured by the C-SSRS

Time frame: From signing of informed consent form up to 70 days after final dose of study treatment (Up to 66.6 months)