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

Parkinson Disease Clinical Trial

— LIGHTHOUSE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05418673
• Other study ID #: 283PD302
• Secondary ID: 2022-000747-77
• Status: Terminated
• Phase: Phase 3
• Start date: August 26, 2022
• Est. completion date: July 27, 2023

Study information

• Verified date: December 2023
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: July 27, 2023
• Est. primary completion date: July 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Biogen	Denali Therapeutics Inc.

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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