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

NCT05418673 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 283PD3022022-000747-77
• Study Type: interventional
• Target: 7
• Locations: 6 countries
• Sites: 27

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.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III

  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 Parkinson's disease (PD).

  From Week 96 to Week 180

Secondary Outcomes (5)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From the first dose (Day 1) of the study drug up to the end of follow-up (up to 336 days)

• Time to Confirmed Worsening in MDS-UPDRS Part II Score

  From Week 96 to Week 180

• Change From Baseline in MDS-UPDRS Parts II and III Combined Score at Week 96

  Baseline, Week 96

• Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score

  From Week 96 to Week 180

• Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score at Week 96

  Baseline, Week 96

Study Arms (2)

BIIB122 225 mg

EXPERIMENTAL

Participants will receive 225 mg of BIIB122 tablets, orally, once daily (QD) for up to 180 weeks.

Drug: BIIB122

BIIB122-Matching Placebo

PLACEBO COMPARATOR

Participants will receive BIIB122-matching placebo tablets, orally, QD for up to 180 weeks.

Drug: BIIB122-Matching Placebo

Interventions

BIIB122 DRUG

Administered as specified in the treatment arm.

Also known as: DNL151

BIIB122 225 mg

BIIB122-Matching Placebo DRUG

Administered as specified in the treatment arm.

BIIB122-Matching Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Biogen: lead
• Denali Therapeutics Inc.: collaborator

Study Sites (27)

University of California San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Rocky Mountain Movement Disorders Center, PC

Englewood, Colorado, 80113, United States

Location

Parkinson's Disease and Movement Disorders Center

Boca Raton, Florida, 33486, United States

Location

USF Health Byrd Institute

Tampa, Florida, 33613, United States

Location

University of Kansas Medical Center Research Institute, Inc.

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mount Sinai Beth Israel

New York, New York, 10003, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Evergreen Hospital Medical Center

Kirkland, Washington, 98034, United States

Location

Inland Northwest Research

Spokane, Washington, 99202, United States

Location

Hôpital de la Timone

Marseille, Bouches-du-Rhône, 13385, France

Location

Hopital Purpan

Toulouse, Haute Garonne, 31059, France

Location

CHU Rennes - Hopital Pontchaillou

Rennes, Ille Et Vilaine, 35033, France

Location

Centre Hospitalier Universitaire de Lyon-Hospices Civils de Lyon-Hopital Pierre Wertheimer

Bron, Rhone, 69500, France

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, 75013, France

Location

Universitaetsklinikum Tuebingen

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, 1307, Germany

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Hospital General de Catalunya

Sant Cugat del Vallès, Barcelona, 8190, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 38003, Spain

Location

Hospital Universitario Donostia

Donostia / San Sebastian, Guipuzcoa, 20014, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Ninewells Hospital

Dundee, Tayside Region, DD1 9SY, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

DNL151

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Limitations and Caveats

Sponsor decided to stop study based on operational and strategic considerations and not for reasons related to efficacy/safety. Due to the early cessation of the study before participants reached the time window for efficacy assessments, efficacy analysis was not possible.

Results Point of Contact

• Title: US Biogen Clinical Trial Center
• Organization: Biogen

clinicaltrials@biogen.com

866-633-4636

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2022
• First Posted: June 14, 2022
• Study Start: August 26, 2022
• Primary Completion: July 27, 2023
• Study Completion: July 27, 2023
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

IT (1); GB (1); DE (2); US (12); FR (5); ES (6)