Clinical trial NCT05418673: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Parkinson Disease
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Denali Therapeutics Inc.
First posted: 2022-06-14
Enrollment: 7
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Time to Confirmed Worsening in Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts II and III
timeFrame: From Week 96 to Week 180
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the first dose (Day 1) of the study drug up to the end of follow-up (up to 336 days)
measure: Time to Confirmed Worsening in MDS-UPDRS Part II Score
timeFrame: From Week 96 to Week 180
measure: Change From Baseline in MDS-UPDRS Parts II and III Combined Score at Week 96
timeFrame: Baseline, Week 96
measure: Time to Confirmed Worsening in Modified Schwab and England Activities of Daily Living Scale (mSE-ADL) Score
timeFrame: From Week 96 to Week 180
measure: Change From Baseline in MDS-UPDRS Parts I, II, and III Combined Score at Week 96
timeFrame: Baseline, Week 96
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco (UCSF)
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Movement Disorders Center, PC
state: Colorado
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Institute
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute, Inc.
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Mount Sinai Beth Israel
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Kirkland
country: United States
facility: Evergreen Hospital Medical Center
state: Washington
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Marseille
country: France
facility: Hôpital de la Timone
state: Bouches-du-Rhône
city: Toulouse
country: France
facility: Hopital Purpan
state: Haute Garonne
city: Rennes cedex 09
country: France
facility: CHU Rennes - Hopital Pontchaillou
state: Ille Et Vilaine
city: Bron
country: France
facility: Centre Hospitalier Universitaire de Lyon-Hospices Civils de Lyon-Hopital Pierre Wertheimer
state: Rhone
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
state: Baden Wuerttemberg
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico Carlo Besta
city: Sant Cugat del Valles
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: San Sebastian
country: Spain
facility: Hospital Universitario Donostia
state: Guipuzcoa
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Tayside Region
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: