Parkinson Disease
Conditions
Keywords
Early-stage Parkinson Disease
Brief summary
In this study, researchers will learn more about BIIB122 in participants with early-stage Parkinson's disease (PD). The study will include adults aged 30 to 80 who were diagnosed with PD within 2 years of starting the study. The main objective of the study is to learn about the effect BIIB122 has on slowing down the worsening of PD symptoms. The main question researchers want to answer is: \- How long does it take for PD symptoms to worsen during BIIB122 treatment? Researchers will answer this and other questions by measuring the symptoms of PD over time using a variety of scoring tools. These include the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the modified Schwab and England Activities of Daily Living Scale (mSE-ADL). The MDS-UPDRS is used to measure symptoms of PD. It has 4 parts: Part I, II, III, and IV. Each part measures different aspects of motor and non-motor symptoms. The mSE-ADL measures a participant's ability to perform daily activities or personal chores. Researchers will also learn more about the safety of BIIB122. They will check participants for adverse events. Adverse events are unwanted health problems that may or may not be caused by the study drug. The study will be done as follows: * Participants will be randomly assigned to take either BIIBB122 or placebo. A placebo looks like the study drug but contains no real medicine. * Neither the researchers nor the participants will know if the participants are receiving BIIB122 or placebo. * Participants will take BIIB122 or placebo tablets by mouth once a day. * The treatment period for each participant will last between 48 and 144 weeks. * There will be a safety follow-up period for 2 weeks after the last dose of BIIB122. * In total, participants will have up to 29 study visits. * Participants will stay in the study for at least 1 year, up to about 3 years.
Detailed description
BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of leucine-rich repeat kinase 2 (LRRK2). Participants who completed the early termination (ET) visit of the study 283PD302 (NCT05418673) would be eligible for screening of this study and if enrolled, these participants are not eligible for the sub studies of 283PD201.
Interventions
DRUGBIIB122
Administered as specified in the treatment arm
Administered as specified in the treatment arm
Sponsors
Denali Therapeutics Inc.
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria within 2 years of the Screening Visit, inclusive, and at least 30 years of age at the time of diagnosis * Modified Hoehn and Yahr scale stages 1 to 2 (in OFF state), inclusive, at screening * MDS-UPDRS Parts II and III (in OFF state) combined score less than or equal to (≤)50 at screening Key
Exclusion criteria
* Clinically significant neurological disorder other than PD, including but not limited to stroke, dementia, or seizure, within 5 years of screening visit, in the opinion of the Investigator * Clinical evidence of atypical parkinsonism (e.g., multiple-system atrophy or progressive supranuclear palsy) or evidence of drug-induced parkinsonism. * Montreal Cognitive Assessment (MoCA) score \<24 at the screening visit. NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Combined Score Over the Treatment Period | Up to Week 144 | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (Range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (Range 0-132). Part III contains 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Part II and III combined score equals the sum of Parts II and III (Range 0-184). A higher score indicates more severe symptoms of PD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Week 144 | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death; in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect or is a medically important event. |
| Time to Confirmed Worsening in MDS-UPDRS Part II Score Over the Treatment Period | Up to a minimum of 48 weeks and a maximum of 144 weeks | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (Range 0-52). It contains 13 questions which are to be completed by the participant. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicates more severe symptoms of PD. |
| Change From Baseline in MDS-UPDRS Parts II and III Combined Score | From Baseline up to Week 48 | MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part II assesses motor experiences of daily living (Range 0-52). It contains 13 questions which are to be completed by the participant. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicates more severe symptoms of PD. Part III assesses the motor signs of PD and is administered by the rater (Range 0-132). Part III contains 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS Parts II and III combined score equals the sum of Part II and III (Range 0-184). A higher score indicates more severe symptoms of PD. |
| Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Over the Treatment Period | Up to a minimum of 48 weeks and a maximum of 144 weeks | Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. The mSE-ADL scale reflects the speed, ease, and independence with which an individual performs daily activities or personal chores with 100% indicating total independence, falling to 0%, which indicates a state of complete dependence. The individual is asked to rate his or her function using an 11-point scale (10% increments), from 100% (completely independent; able to do all chores without slowness, difficulty, or impairment; essentially normal; unaware of any difficulty) to 0% (vegetative functions such as swallowing, bladder and bowels are not functioning; bedridden). The lower the score, the worse the functional status. |
| Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score | From Baseline up to Week 48 | MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of 4 parts. Part I assesses non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and is assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which are to be completed by the participant (Range 0-28). Part II assesses motor experiences of daily living (Range 0-52). It contains 13 questions which are to be completed by the participant. Part III assesses the motor signs of PD and is administered by the rater (Range 0-132). Part III contains 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. MDS-UPDRS total score equals the sum of Parts I, II, and III (Range 0-236). A higher score indicates more severe symptoms of PD. |
Countries
Austria, Canada, China, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Spain, United Kingdom, United States
Outcome results
None listed