Clinical trial NCT03976349: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BIIB094 in Adults With Parkinson's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Lead sponsor: Biogen
Sponsor class: INDUSTRY
Collaborators: name: Ionis Pharmaceuticals, Inc.
First posted: 2019-06-06
Enrollment: 62
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Part A: Screening (Day -42) up to Day 85, Part B: Screening (Day -77) up to Day 253
Secondary outcomes:
measure: Serum Concentrations of BIIB094
timeFrame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
measure: Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUCinf) of BIIB094
timeFrame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
measure: Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of BIIB094
timeFrame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
measure: Maximum Concentration (Cmax) of BIIB094
timeFrame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
measure: Time to Reach Maximum Concentration (Tmax) of BIIB094
timeFrame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
measure: Terminal Elimination Half-Life (t1/2) of BIIB094
timeFrame: Part A: pre-dose through Day 57, Part B: pre-dose through Day 169
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University PD and Movement Disorders Center
state: Illinois
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research
state: Tennessee
city: Spokane
country: United States
facility: Inland Northwest Research
state: Washington
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Montreal Neurological Institute and Hospital
state: Quebec
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center
city: Bergen
country: Norway
facility: Neuro-SysMed Center
city: Trondheim
country: Norway
facility: St. Olav University Hospital
city: Barakaldo
country: Spain
facility: Laboratorios de Investigación Biocruces 3., Hospital de Cruces
state: Bizkaia
city: Barcelona
country: Spain
facility: Hospital General de Catalunya
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Sevilla
country: Spain
facility: Research Site
city: London
country: United Kingdom
facility: Queen Square (Neurology) CRF Site Institute of Neurology & the National Hospital for Neurology and Neurosurgery UCLH
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: