Safety and Pharmacodynamic Effects of BIIB122 in Participants With LRRK2-Associated Parkinson's Disease (LRRK2-PD)

NCT06602193 | Recruiting Phase 2 FDA Drug

• 1 other identifier: DNLI-C-0009
• Study Type: interventional
• Target: 50
• Locations: 4 countries
• Sites: 20

Brief Summary

This Phase 2a, multicenter, randomized, 12-week double-blind, placebo-controlled, parallel-group study, followed by an OLE, is designed to evaluate the safety, tolerability, and pharmacodynamic effects of BIIB122 in participants with LRRK2-PD. LRRK2-PD is defined as Parkinson's Disease (PD) in individuals who are heterozygous or homozygous carriers of a pathogenic LRRK2 variant that increases LRRK2 kinase activity.

Conditions

Parkinson Disease

Keywords

LRRK2; Movement Disorders

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) with BIIB122 compared with placebo over the 12-week double-blind period

  12 weeks

Secondary Outcomes (2)

• Change from baseline in whole-blood pS935 LRRK2 with BIIB122 compared with placebo at Week 12

  12 weeks

• Change from baseline in urine BMP with BIIB122 compared with placebo at Week 12

  12 weeks

Other Outcomes (1)

• Incidence of TEAEs and SAEs during the OLE period

  2.5 years

Study Arms (2)

BIIB122 225 mg

EXPERIMENTAL

Oral 225 mg dose, once daily (QD)

Drug: BIIB122 225 mg

BIIB122 Matching Placebo

PLACEBO COMPARATOR

Oral BIIB122 matching placebo, once daily (QD)

Other: BIIB122-Matching Placebo

Interventions

BIIB122 225 mg DRUG

Administered as specified in the treatment arm

Also known as: DNL151

BIIB122 225 mg

BIIB122-Matching Placebo OTHER

Administered as specified in the treatment arm

BIIB122 Matching Placebo

Eligibility Criteria

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

You may qualify if:

• For heterozygous pathogenic LRRK2 mutation carriers: ≥ 30 to ≤ 80 years
• For homozygous pathogenic LRRK2 mutation carriers: ≥ 30 years
• Have screening genetic test results verifying the presence of a pathogenic LRRK2 variant.
• Have a clinical diagnosis of PD meeting the Movement Disorder Society Clinical Diagnostic Criteria.

You may not qualify if:

• Have a history of any clinically significant neurological disorder other than PD, including, but not limited to, stroke and dementia, in the opinion of the investigator, within 5 years of the screening visit.
• Have clinical evidence of atypical parkinsonism (eg, multiple-system atrophy or progressive supranuclear palsy) or evidence of drug-induced parkinsonism.
• Have previously participated or are currently participating in the BIIB122 LUMA study (Study 283PD201).
• Have previously participated or are currently participating in a gene therapy study for PD.
• Have a history of brain surgical intervention for PD (eg, deep-brain stimulation, pallidotomy).
• Have any physical condition that may confound the motor assessment (MDS-UPDRS) over time (eg, severe arthritis, severe dyskinesias, traumatic injuries with permanent physical disability).
• Abnormal vitals including Blood Pressure, Heart Rate, or Body Temperature
• Have abnormal PFT results at screening

Sponsors & Collaborators

• Denali Therapeutics Inc.: lead
• Biogen: collaborator

Study Sites (20)

Cedars-Sinai Department of Neurology

Los Angeles, California, 90048, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

Parkinson's Disease and Movement Disorders Center

Boca Raton, Florida, 33486, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Ichan School of Medicine at Mount Sinai/Beth Israel Downtown-Movement Disorder Center

New York, New York, 10003, United States

RECRUITING

Evergreen Health Laboratory

Kirkland, Washington, 98034, United States

RECRUITING

Inland Northwest Research

Spokane, Washington, 99202, United States

RECRUITING

Technische Universität Dresden

Dresden, Germany

RECRUITING

University of Lübeck

Lübeck, Germany

RECRUITING

University Hospital Tübingen

Tübingen, Germany

RECRUITING

Rabin Medical Center

Petah Tikva, Israel

RECRUITING

Movement Disorders Institute, Sheba Medical Center

Ramat Gan, Israel

RECRUITING

Tel Aviv Medical Center

Tel Aviv, Israel

RECRUITING

Hospital Clinic de Barcelona

Barcelona, Spain

RECRUITING

Hospital Universitari General de Catalunya

Barcelona, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, Spain

RECRUITING

Hospital Universitario Donostia

Donostia / San Sebastian, Spain

RECRUITING

Universitary Hospital La Princesa

Madrid, Spain

RECRUITING

IDIVAL/University Hospital Marques de Valdecilla

Santander, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Spain

RECRUITING

MeSH Terms

Conditions

Parkinson Disease; Movement Disorders

Interventions

DNL151

Condition Hierarchy (Ancestors)

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

Study Officials

• Danna Jennings, MD

  Denali Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials at Denali Therapeutics

CONTACT

clinical-trials@dnli.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: September 19, 2024
• Study Start: October 24, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): February 28, 2028
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); US (7); IL (3); ES (7)