BIIB122 for Parkinson's Disease

Recruiting at 17 trial locations

Overseen By Clinical Trials at Denali Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Denali Therapeutics Inc.

Disqualifiers: Stroke, Dementia, Atypical parkinsonism, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BIIB122 (also known as DNL151) for individuals with a specific type of Parkinson's Disease linked to a genetic variation in the LRRK2 gene. The goal is to determine the safety of BIIB122 and its effects on the disease compared to a placebo (a pill with no active medicine). Individuals diagnosed with Parkinson's and possessing a genetic test showing the LRRK2 variant might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that BIIB122 is likely to be safe for humans?

Research has shown that BIIB122 is generally safe and well-tolerated. Studies have found that the doses used in trials effectively blocked LRRK2 activity without major safety concerns. In earlier tests with both healthy individuals and those with Parkinson's Disease, BIIB122 did not cause significant side effects, indicating it was mostly free from unwanted reactions. This suggests that BIIB122 could be safe for many participants, although individual experiences may vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's Disease?

Researchers are excited about BIIB122 for Parkinson's Disease because it introduces a new approach by targeting LRRK2, a protein linked to the progression of Parkinson's. Unlike current treatments that mainly address symptoms, like dopamine replacement therapies (e.g., levodopa), BIIB122 aims to modify the disease process itself. This could not only manage symptoms but also potentially slow down the disease's progression, offering new hope for better long-term outcomes in patients.

What evidence suggests that BIIB122 might be an effective treatment for Parkinson's Disease?

Research has shown that BIIB122, which participants in this trial may receive, might help slow the worsening of symptoms in people with Parkinson's Disease who have a specific gene variant called LRRK2. This gene is linked to increased activity of a protein called LRRK2 kinase, believed to contribute to Parkinson's progression. Studies have found that BIIB122 effectively reduces the activity of LRRK2 kinase, which might help manage the disease. Early findings suggest that reducing this activity could affect biological processes related to Parkinson’s, potentially benefiting patients. While more research is needed, these initial results are promising for those with this form of Parkinson's. ^{1 4 5 6 7}

Who Is on the Research Team?

Danna Jennings, MD

Principal Investigator

Denali Therapeutics

Are You a Good Fit for This Trial?

This trial is for people aged 30-80 with Parkinson's Disease who carry a specific genetic change (LRRK2 variant) that increases LRRK2 activity. They must meet the clinical criteria for PD diagnosis and have verified genetic test results showing they have this mutation.

Inclusion Criteria

I have been diagnosed with Parkinson's disease according to specific criteria.

I am between 30 and 80 years old with a specific genetic mutation.

I am 30 years or older with a specific genetic mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either BIIB122 225 mg or a matching placebo once daily for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

What Are the Treatments Tested in This Trial?

Interventions

• BIIB122

Trial Overview The study tests BIIB122, a potential new treatment for Parkinson's Disease, against a placebo. Participants are randomly assigned to receive either BIIB122 or a fake pill without active ingredients, in order to compare effects over 12 weeks.

How Is the Trial Designed?

Group I: BIIB122 225 mg Experimental Treatment 1 Intervention

Oral 225 mg dose, once daily (QD)

Group II: BIIB122 Matching Placebo Placebo Group 1 Intervention

Oral BIIB122 matching placebo, once daily (QD)

Who Is Running the Clinical Trial?

Denali Therapeutics Inc.

Lead Sponsor

Trials

24

Recruited

1,900+

Biogen

Industry Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Published Research Related to This Trial

Mutations in the FBXO7 gene lead to PARK15, a neurodegenerative disease characterized by severe parkinsonism, and the depletion of the FBXO7 isoform 1 in patients suggests its crucial role in maintaining brain neurons.

The study found that the normal FBXO7 isoform 1 is primarily localized in the nucleus of neurons, and its mislocalization or instability due to mutations may contribute to the disease's pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of nuclear activity of the FBXO7 protein in patients with parkinsonian-pyramidal syndrome (PARK15). Zhao, T., De Graaff, E., Breedveld, GJ., et al.[2021]

A new Turkish family was identified with a homozygous mutation in the FBXO7 gene, which is linked to juvenile parkinsonism, highlighting the genetic diversity of this condition.

Affected siblings showed progressive parkinsonism and mental retardation, with a limited response to dopaminergic medications due to side effects, indicating the complexity of treatment in this genetic form of parkinsonism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new Turkish family with homozygous FBXO7 truncating mutation and juvenile atypical parkinsonism. Yalcin-Cakmakli, G., Olgiati, S., Quadri, M., et al.[2014]

Mutations in the FBXO7 gene are linked to PARK15, a form of juvenile parkinsonism, and this study found that FBXO7 protein is widely expressed in the brain, particularly in neurons of the cerebral cortex, putamen, and cerebellum.

FBXO7 was found to colocalize with α-synuclein in Lewy bodies and other inclusions in Parkinson's disease and multiple system atrophy, suggesting that FBXO7 may play a significant role in the development of these synuclein-related neurodegenerative diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FBXO7 immunoreactivity in α-synuclein-containing inclusions in Parkinson disease and multiple system atrophy. Zhao, T., Severijnen, LA., van der Weiden, M., et al.[2013]

In a study using mutated forms of human alpha-synuclein in a rat model of Parkinson's disease, the S129D mutation (mimicking phosphorylation) led to faster dopaminergic fiber loss and earlier motor deficits compared to the S129A mutation (blocking phosphorylation).

The S129A mutation showed a neuroprotective effect, resulting in larger pathological inclusions and slower degeneration, indicating that phosphorylation at S129 may exacerbate neurodegeneration in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ser129D mutant alpha-synuclein induces earlier motor dysfunction while S129A results in distinctive pathology in a rat model of Parkinson's disease. Febbraro, F., Sahin, G., Farran, A., et al.[2013]

The P123H mutation in β-synuclein (βS) transforms it from a protective, nontoxic protein into a toxic one that accelerates α-synuclein (αS) fibril formation, highlighting the mutation's significant impact on protein behavior in the context of neurodegenerative diseases.

The study reveals that the C-terminal region of βS is crucial for its protective function against αS aggregation, suggesting that targeting this area could be a potential therapeutic strategy for conditions like Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The loss of inhibitory C-terminal conformations in disease associated P123H β-synuclein. Janowska, MK., Baum, J.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05348785

NCT05348785 | A Study to Learn About the Safety of ... The main objective of the study is to learn about the effect BIIB122 has on slowing down the worsening of PD symptoms.

2. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29297

LRRK2 Inhibition by BIIB122 in Healthy Participants and ... BIIB122 treatment achieved peripheral LRRK2 kinase inhibition levels sufficient to modulate peripheral BMP, an effect that is likely translated ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11076002/

LRRK2-targeting therapies march through the Valley of Death The stakes are high. If BIIB122 were successful in slowing PD, there will be a wave of renewed enthusiasm not only for more LRRK2-targeting therapeutics, but ...

4. neurologylive.com neurologylive.com/view/biogen-denali-terminate-phase-3-lighthouse-study-biib122-lrrk2-parkinson-disease

Biogen and Denali Terminate Phase 3 LIGHTHOUSE ... To understand whether BIIB122 slows the worsening of symptoms, investigators are evaluating patients on Movement Disorder Society-Unified ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05418673

NCT05418673 | A Study to Assess if BIIB122 Tablets Are ... 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36807624/

LRRK2 Inhibition by BIIB122 in Healthy Participants and ... At generally safe and well-tolerated doses, BIIB122 achieved substantial peripheral LRRK2 kinase inhibition and modulation of lysosomal ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06602193

NCT06602193 | Safety and Pharmacodynamic Effects of ... Also called a data safety and monitoring board, or DSMB. ... Safety and Pharmacodynamic Effects of BIIB122 in Participants With LRRK2-Associated Parkinson's ...