A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson's Disease (REASON)

A Phase 1 Single- and Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB094 Administered Intrathecally to Adults With Parkinson's Disease

The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses of BIIB094 administered via intrathecal (IT) injection to participants with Parkinson's Disease (PD). The secondary objective of this study is to evaluate the pharmacokinetic (PK) profile of BIIB094.The study is open for PD patients with verified presence or absence of variations in the leucine-rich repeated kinase 2 (LRRK2) gene, but also for patients without any verified PD-related genetic variant.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Placebo; Drug: BIIB094

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, QC H3A 2B4
      • Montreal Neurological Institute and Hospital
• Israel
  • Tel Aviv, Israel, 64239
    • Sourasky Medical Center
• Norway
  • Bergen, Norway, 5053
    • Neuro-SysMed Center
  • Trondheim, Norway, 7030
    • St. Olav University Hospital
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Seville, Spain
    • Research Site
  • Bizkaia
    • Barakaldo, Bizkaia, Spain, 48903
      • Laboratorios de Investigación Biocruces 3., Hospital de Cruces
  • Vizcaya
    • Barcelona, Vizcaya, Spain, 08195
      • Hospital General de Catalunya
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • Queen Square (Neurology) CRF Site Institute of Neurology & the National Hospital for Neurology and Neurosurgery UCLH
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University PD and Movement Disorders Center
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • University of Pennsylvania
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty Research
  • Washington
    • Spokane, Washington, United States, 99202
      • Inland Northwest Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
• Diagnosed with PD within 7 years at the time of initial enrollment (i.e., at time of SAD enrollment for rollover participants), without major motor fluctuations or dyskinesia that may interfere with study treatment and assessments in the opinion of the investigator after consultation with the Sponsor.
• Modified Hoehn and Yahr Stage ≤ 3.

Key Exclusion Criteria:

• Montreal Cognitive Assessment (MoCA) score less than (<) 23, dementia, or other significant cognitive impairment that, in the opinion of the Investigator, would interfere with study evaluation.
• History of any brain surgery for PD or a history of focused ultrasound treatment at any time; or history of neuromodulation procedures.
• Transient ischemic attack or stroke or any unexplained loss of consciousness within 1 year before Screening.
• History of unstable angina, myocardial infarction, chronic heart failure, or clinically significant conduction abnormalities within 1 year before Screening.
• Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within 3 months before dosing (Day 1) or glycosylated hemoglobin value greater than or equal to (≥) 8 percent (%) at Screening.
• History or positive test result at Screening for human immunodeficiency virus.
• History or positive test result at Screening for hepatitis C virus antibody.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A (SAD): BIIB094 Dose 1; Participants will receive a single IT injection of BIIB094 during Part A [Single Ascending Dose (SAD)].	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part A (SAD): BIIB094 Dose 2; Participants will receive a single IT injection of BIIB094 during Part A (SAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part A (SAD): BIIB094 Dose 3; Participants will receive a single IT injection of BIIB094 during Part A (SAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part A (SAD): BIIB094 Dose 4; Participants will receive a single IT injection of BIIB094 during Part A (SAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part A (SAD): BIIB094 Dose 5; Participants will receive a single IT injection of BIIB094 during Part A (SAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part A (SAD): BIIB094 Dose 6; Participants will receive a single IT injection of BIIB094 during Part A (SAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part B (MAD): BIIB094 Dose 1; Participants will receive a single IT injection of BIIB094 on multiple days during Part B [Multiple Ascending Dose (MAD)].	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part B (MAD): BIIB094 (Non LRRK2) Dose 2; Participants [Non leucine-rich repeat kinase 2 (Non LRRK2)] will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part B (MAD): BIIB094 (LRRK2) Dose 2; Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part B (MAD): BIIB094 (Non LRRK2) Dose 3; Participants (Non LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Experimental: Part B (MAD): BIIB094 (LRRK2) Dose 3; Participants (LRRK2) will receive a single IT injection of BIIB094 on multiple days during Part B (MAD).	Drug: BIIB094; Administered as specified in the treatment arm.
Placebo Comparator: Part A (SAD): Matching Placebo; Participants will receive matching placebo during Part A [Single Ascending Dose (SAD)].	Drug: Placebo; Administered as specified in the treatment arm.
Placebo Comparator: Part B (MAD): Matching Placebo; Participants will receive matching placebo on multiple days during Part B (MAD).	Drug: Placebo; Administered as specified in the treatment arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An 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 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); however, this does not include an event that, had it occurred in a more severe form, might have caused death; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in a congenital anomaly/birth defect; is a medically important event.	Part A: Screening (Day -42) up to Day 85, Part B: Screening (Day -77) up to Day 253

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Concentrations of BIIB094	Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BIIB094	Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of BIIB094	Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Maximum Concentration (Cmax) of BIIB094	Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Time to Reach Maximum Concentration (Tmax) of BIIB094	Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Terminal Elimination Half-Life (t1/2) of BIIB094	Part A: pre-dose through Day 57, Part B: pre-dose through Day 169

Collaborators and Investigators

• Sponsor: Ionis Pharmaceuticals, Inc.
• Collaborators: Ionis Pharmaceuticals, Inc.
• Investigators: Study Director: Medical Director, Biogen

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): August 12, 2024

Study Registration Dates

• First Submitted: June 4, 2019
• First Submitted That Met QC Criteria: June 4, 2019
• First Posted (Actual): June 6, 2019

Study Record Updates

• Last Update Posted (Estimated): September 23, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Substandard Drugs; Pharmaceutical Preparations; BIIB094
• Other Study ID Numbers: 254PD101; 2018-002995-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No