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)

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

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.

Study Overview

• Status: Terminated
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: BIIB122; Drug: BIIB122-Matching Placebo

Detailed Description

BIIB122 is an investigational central nervous system-penetrant small molecule inhibitor of LRRK2 kinase

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: US Biogen Clinical Trial Center; Phone Number: 866-633-4636; Email: clinicaltrials@biogen.com
• Study Contact Backup: Name: Global Biogen Clinical Trial Center; Email: clinicaltrials@biogen.com

Study Locations

• France
  • Paris, France, 75013
    • Groupe Hospitalier Pitie-Salpetriere
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13385
      • Hopital de la Timone
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • Hopital Purpan
  • Ille Et Vilaine
    • Rennes cedex 09, Ille Et Vilaine, France, 35033
      • CHU Rennes - Hôpital Pontchaillou
  • Rhone
    • Bron, Rhone, France, 69500
      • Centre Hospitalier Universitaire de Lyon-Hospices Civils de Lyon-Hopital Pierre Wertheimer
• Germany
  • Dresden, Germany, 1307
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Baden Wuerttemberg
    • Tuebingen, Baden Wuerttemberg, Germany, 72076
      • Universitaetsklinikum Tuebingen
• Italy
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Neurologico Carlo Besta
• Spain
  • Barcelona, Spain, 8035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8036
    • Hospital Clinic de Barcelona
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocío
  • Barcelona
    • Sant Cugat del Valles, Barcelona, Spain, 8190
      • Hospital General de Catalunya
  • Cantabria
    • Santander, Cantabria, Spain, 38003
      • Hospital Universitario Marques de Valdecilla
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20014
      • Hospital Universitario Donostia
• United Kingdom
  • Tayside Region
    • Dundee, Tayside Region, United Kingdom, DD1 9SY
      • Ninewells Hospital
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco (UCSF)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Movement Disorders Center, PC
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center
    • Tampa, Florida, United States, 33613
      • USF Health Byrd Institute
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute, Inc.
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10003
      • Mount Sinai Beth Israel
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Hospital Medical Center
    • Spokane, Washington, United States, 99202
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIIB122 225 mg; Participants will receive 225 mg of BIIB122 tablets, orally, once daily (QD) for up to 180 weeks.	Drug: BIIB122; Administered as specified in the treatment arm.; Other Names: DNL151
Placebo Comparator: BIIB122-Matching Placebo; Participants will receive BIIB122-matching placebo tablets, orally, QD for up to 180 weeks.	Drug: BIIB122-Matching Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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.	Up to Week 180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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.	AEs: Day 1 up to Week 187; SAEs: Screening up to Week 187
Time to Confirmed Worsening in MDS-UPDRS Part II Score Over the Treatment Period	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.	Up to Week 180
Change From Baseline in MDS-UPDRS Parts II and III Combined Score	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.	Baseline up to Week 96
Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score	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.	Baseline up to Week 96
Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score Over the Treatment Period	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.	Up to Week 180

Collaborators and Investigators

• Sponsor: Biogen
• Collaborators: Denali Therapeutics Inc.
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

Helpful Links

• Click here to learn more about this trial, visit our study website.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Actual): July 27, 2023
• Study Completion (Actual): July 27, 2023

Study Registration Dates

• First Submitted: June 10, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Estimated): December 20, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: 283PD302; 2022-000747-77 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No