A Study to Assess if BIIB122 Tablets Are Safe and Can Slow Worsening of Early-Stage Parkinson's Disease in Participants With Specific LRRK2 Genetic Variants Between the Ages of 30 and 80 Using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (LIGHTHOUSE)

• ClinicalTrials.gov Identifier: NCT05418673
• Recruitment Status: Terminated
• First Posted: June 14, 2022
• Last Update Posted: December 20, 2023
• Sponsor: Biogen
• Collaborator: Denali Therapeutics Inc.
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: June 10, 2022
• First Posted Date: June 14, 2022
• Last Update Posted Date: December 20, 2023
• Actual Study Start Date: August 26, 2022
• Actual Primary Completion Date: July 27, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2022)

Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III Over the Treatment Period [ Time Frame: Up to Week 180 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 25, 2023)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: AEs: Day 1 up to Week 187; SAEs: Screening up to Week 187 ]
  An adverse event (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 [ Time Frame: Up to Week 180 ]
  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 [ Time Frame: Baseline up to Week 96 ]
  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. Positive change from baseline indicates severe PD.
• Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score Over the Treatment Period [ Time Frame: Up to Week 180 ]
  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 [ Time Frame: Baseline up to Week 96 ]
  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. Positive change from baseline indicates severe PD.

Original Secondary Outcome Measures (submitted: June 10, 2022)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: AEs: Day 1 up to Week 187; SAEs: Screening up to Week 187 ]
  An adverse event (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 [ Time Frame: Up to Week 180 ]
  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 [ Time Frame: Baseline up to Week 96 ]
  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. Positive change from baseline indicates severe PD.
• Time to Confirmed Worsening in Schwab and England Activities of Daily Living Scale (SE-ADL) Score Over the Treatment Period [ Time Frame: Up to Week 180 ]
  Time to confirmed worsening is defined as a worsening event sustained over 2 consecutive assessments. The SE-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 [ Time Frame: Baseline up to Week 96 ]
  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. Positive change from baseline indicates severe PD.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Assess if BIIB122 Tablets Are Safe and Can Slow Worsening of Early-Stage Parkinson's Disease in Participants With Specific LRRK2 Genetic Variants Between the Ages of 30 and 80 Using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale
• Official Title: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Determine the Efficacy and Safety of BIIB122/DNL151 in Participants With Parkinson's Disease and Pathogenic LRRK2 Variants

Brief Summary

In this study, researchers will learn more about a study drug called BIIB122 in participants with early-stage Parkinson's disease (PD). The study will focus on participants with a specific genetic variant in their LRRK2 gene.

The main question researchers are trying to answer is if taking BIIB122 slows the worsening of PD more than placebo in the early stages of PD.

To help answer this question, researchers will use a questionnaire called the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, also known as the MDS-UPDRS.

• The MDS-UPDRS measures impairment and disability in people living with PD. It was created in the 1980s and is one of the most used rating scales for PD symptoms.
• The MDS-UPDRS has 4 parts, and a higher score means more severe PD symptoms.
• Part I assesses non-motor experiences of daily living, including but not limited to memory loss, problems sleeping, pain, depression, and anxiety.
• Part II measures motor experiences of daily living.
• Part III is the results of a motor symptoms exam by a medical professional.
• Part IV records PD complications caused by motor symptoms.

Researchers will also learn more about the safety of BIIB122.

A description of how the study will be done is given below.

• Participants will take BIIB122 or a placebo as tablets by mouth. A placebo looks like the study drug but contains no real medicine.
• Participants will be in the study for 103 weeks to 187 weeks. This includes the screening and follow-up periods.
• Participants will take BIIB122 or placebo 1 time a day for 96 to 180 weeks.
• Participants can continue to take certain medications for PD. Participants must be on the same dose of medication for at least 90 days before the study begins.
• Participants will visit the clinic less often as the study continues, ranging every 4 weeks to every 24 weeks.

• Detailed Description: BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of LRRK2 kinase
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson Disease

Intervention

• Drug: BIIB122
  Administered as specified in the treatment arm.
  Other Name: DNL151
• Drug: BIIB122-Matching Placebo
  Administered as specified in the treatment arm.

Study Arms

• Experimental: BIIB122 225 mg
  Participants will receive 225 mg of BIIB122 tablets, orally, once daily (QD) for up to 180 weeks.
  Intervention: Drug: BIIB122
• Placebo Comparator: BIIB122-Matching Placebo
  Participants will receive BIIB122-matching placebo tablets, orally, QD for up to 180 weeks.
  Intervention: Drug: BIIB122-Matching Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 19, 2023): 7
• Original Estimated Enrollment (submitted: June 10, 2022): 400
• Actual Study Completion Date: July 27, 2023
• Actual Primary Completion Date: July 27, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria within 5 years of the Screening Visit, inclusive, and at least 30 years of age at the time of diagnosis
• Modified Hoehn and Yahr scale (mHY), Stages 1 to 2.5 (in OFF state), inclusive, at Screening
• MDS-UPDRS Parts II and III (in OFF state) combined score ≤40 at Screening
• Screening genetic test results verifying the presence of a pathogenic leucine-rich repeat kinase 2 (LRRK2) variant

Key Exclusion Criteria:

• Clinically significant neurologic 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Germany, Italy, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05418673
• Other Study ID Numbers: 283PD302; 2022-000747-77 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
• URL: https://vivli.org/

• Current Responsible Party: Biogen
• Original Responsible Party: Same as current
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: Denali Therapeutics Inc.

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: December 2023