Clinical trial NCT04658186: A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease
Official title: A Double-Blind, Placebo-Controlled, Randomized, 18-Month Phase 2a Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Oral UCB0599 in Study Participants With Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Early-stage Parkinson's Disease
Keywords: Early-stage parkinson's disease
UCB0599
Phase 2
Early-stage PD
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
Collaborators: name: The Parkinson Study Group
First posted: 2020-12-08
Enrollment: 496
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess the safety and tolerability of UCB0599 and to demonstrate the superiority of UCB0599 over placebo with regard to clinical symptoms of disease progression over 12 and 18 months in participants diagnosed with early-stage Parkinson's Disease.


Eligibility criteria: Inclusion Criteria:

* Study participant must be 40 to 75 years of age inclusive, at the time of signing the informed consent
* Study participant has Parkinson's Disease (PD), with a diagnosis made by a neurologist according to the 2015 Movement Disorder Society criteria within 2 years of Baseline Visit (including diagnosis during Screening)
* The following diagnostic criteria must be met: bradykinesia AND at least ONE of the following: muscular rigidity, or resting tremor
* A Screening Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT), or a historical DaT-SPECT within 3 months of the Screening Visit that has been qualified by the central reader, shows evidence of dopamine transporter deficit per study requirements and as determined by a central reader
* Study participant is in the ≤2.5 modified Hoehn and Yahr stage at Screening
* Study participant has never taken medications for the treatment of motor symptoms of PD and is not expected to require starting symptomatic treatment (ST) with a high likelihood in the next 6 months as far as clinical judgement allows
* Study participant has never taken part in disease-modifying treatment studies directed at neurodegenerative disease (NDD)
* Study participant does not take N-acetyl cysteine or other cysteine donors or glutathione precursors on a regular basis as a food supplement
* Study participant is willing, competent, and able to comply with all aspects of the protocol, including follow-up schedule and biospecimen collection
* Study participant has a body mass index (BMI) of 16 to 34kg/m² (inclusive)
* Contraception i) A male participant must agree to use contraception during the Treatment Period and for at least 90 days after the last dose ofstudy medication and refrain from donating sperm during this period ii) A female participant is eligible to participate if she is not pregnant, not breastfeeding, andat least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the Treatment Period and for at least 1 month after the last dose of study medication. The study participant must have a negative serum pregnancy test at Screening, which is to be confirmed negative by urine testing prior to the first dose of study medication at Baseline (Visit 3). If oral contraception is used, an additional barrier method will be required during the study as a study medication related-gastrointestinal upset or a drug interaction by CYP3A4 induction could interfere with efficacy

Exclusion Criteria:

* Study participant has a known hypersensitivity to any components (and/or its excipients) of the study medication or comparative drugs as stated in the protocol
* Study participant has a brain magnetic resonance imaging (MRI) scan performed during Screening indicative of a clinically significant abnormality or a historical MRI scan during the 6 months before Screening Visit 1 of sufficient quality to show such abnormalities. In case of doubt, the significance is determined on a case-by-case basis in close collaboration with the Medical Monitor and should not include abnormalities like age-appropriate brain atrophy, minor white matter signals, or mild vasculopathy
* Study participant has any contraindication for the brain MRI or Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) imaging
* Study participant has a Montreal Cognitive Assessment (MoCA) score less than 23, indicating mild cognitive impairment or other significant cognitive impairment or clinical dementia at Screening that, in the opinion of the Investigator, would interfere with study evaluation
* Study participant has abnormalities in lumbar spine previously known or determined by a Screening lumbar x-ray (if conducted) that could preclude lumbar puncture, in the opinion of the Investigator. The participant must be excluded from lumbar puncture but not from study participation
* Study participant has clinically significant electrocardiogram (ECG) abnormality at Screening, in the opinion of the Investigator
* Study participant has past history of use of medications for the treatment of motor symptoms of PD. Short (up to 4 weeks) past use of medications for the treatment of motor symptoms is permitted following a sufficient washout period. Medications included are: levodopa (maximum 400mg per day), dopamine agonists, monoamine oxidase B (MAO-B) inhibitors, anticholinergics, or amantadine. A sufficient washout period is at least 3 months prior to the Baseline Visit

Primary outcomes:
measure: Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III sum score
timeFrame: From Baseline up to 18 Months
Secondary outcomes:
measure: MDS-UPDRS Part III subscale
timeFrame: From Baseline up to 18 Months
measure: MDS-UPDRS Part III early-stage Parkinson's disease (ePD) subscore on selected items
timeFrame: From Baseline up to 18 Months
measure: MDS-UPDRS Part II subscale
timeFrame: From Baseline up to 18 Months
measure: MDS-UPDRS Part I subscale
timeFrame: From Baseline up to 18 Months
measure: Emerging symptoms as measured by MDS-UPDRS Part II
timeFrame: From Baseline up to 18 Months
measure: Time to worsening of the disease as measured by MDS-UPDRS Part III
timeFrame: From Baseline up to 18 Months
measure: Montreal Cognitive Assessment (MoCA)
timeFrame: From Screening up to 18 Months
measure: Change in Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) mean striatum specific binding ratios (SBR)
timeFrame: From Screening up to 18 Months
measure: Time to start of symptomatic treatment (ST)
timeFrame: From Baseline up to 18 Months
measure: Symptomatic treatment (ST) intake
timeFrame: From Baseline up to 18 Months
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: From Baseline up to 19 Months
measure: Incidence of serious adverse events (SAEs)
timeFrame: From Screening up to 19 Months
measure: Incidence of TEAEs leading to participant withdrawal
timeFrame: From Baseline up to 19 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Pd0053 50140
state: Alabama
city: Phoenix
country: United States
facility: Pd0053 50506
state: Arizona
city: Phoenix
country: United States
facility: Pd0053 50081
state: Arizona
city: Tucson
country: United States
facility: Pd0053 50391
state: Arizona
city: Little Rock
country: United States
facility: Pd0053 50539
state: Arkansas
city: Fountain Valley
country: United States
facility: Pd0053 50519
state: California
city: Fresno
country: United States
facility: Pd0053 50385
state: California
city: La Jolla
country: United States
facility: Pd0053 50416
state: California
city: Los Angeles
country: United States
facility: Pd0053 50118
state: California
city: Englewood
country: United States
facility: Pd0053 50531
state: Colorado
city: Danbury
country: United States
facility: Pd0053 50392
state: Connecticut
city: Farmington
country: United States
facility: Pd0053 50538
state: Connecticut
city: Boca Raton
country: United States
facility: Pd0053 50396
state: Florida
city: Bradenton
country: United States
facility: Pd0053 50524
state: Florida
city: Miami
country: United States
facility: Pd0053 50199
state: Florida
city: Tampa
country: United States
facility: Pd0053 50394
state: Florida
city: Augusta
country: United States
facility: Pd0053 50544
state: Georgia
city: Chicago
country: United States
facility: Pd0053 50401
state: Illinois
city: Chicago
country: United States
facility: Pd0053 50310
state: Illinois
city: Winfield
country: United States
facility: Pd0053 50399
state: Illinois
city: Iowa City
country: United States
facility: Pd0053 50549
state: Iowa
city: Kansas City
country: United States
facility: Pd0053 50074
state: Kansas
city: Lexington
country: United States
facility: Pd0053 50121
state: Kentucky
city: New Orleans
country: United States
facility: Pd0053 50395
state: Louisiana
city: Baltimore
country: United States
facility: Pd0053 50529
state: Maryland
city: Baltimore
country: United States
facility: Pd0053 50547
state: Maryland
city: Boston
country: United States
facility: Pd0053 50243
state: Massachusetts
city: Worcester
country: United States
facility: Pd0053 50546
state: Massachusetts
city: Farmington Hills
country: United States
facility: Pd0053 50386
state: Michigan
city: Saint Paul
country: United States
facility: Pd0053 50536
state: Minnesota
city: Las Vegas
country: United States
facility: Pd0053 50397
state: Nevada
city: New Brunswick
country: United States
facility: Pd0053 50299
state: New Jersey
city: New York
country: United States
facility: Pd0053 50077
state: New York
city: New York
country: United States
facility: Pd0053 50521
state: New York
city: New York
country: United States
facility: Pd0053 50119
state: New York
city: Stony Brook
country: United States
facility: Pd0053 50530
state: New York
city: Williamsville
country: United States
facility: Pd0053 50535
state: New York
city: Cleveland
country: United States
facility: Pd0053 50372
state: Ohio
city: Cleveland
country: United States
facility: Pd0053 50311
state: Ohio
city: Columbus
country: United States
facility: Pd0053 50255
state: Ohio
city: Toledo
country: United States
facility: Pd0053 50527
state: Ohio
city: Tulsa
country: United States
facility: Pd0053 50398
state: Oklahoma
city: Portland
country: United States
facility: Pd0053 50510
state: Oregon
city: Philadelphia
country: United States
facility: Pd0053 50526
state: Pennsylvania
city: Charleston
country: United States
facility: Pd0053 50084
state: South Carolina
city: Knoxville
country: United States
facility: Pd0053 50532
state: Tennessee
city: Memphis
country: United States
facility: Pd0053 50543
state: Tennessee
city: Houston
country: United States
facility: Pd0053 50525
state: Texas
city: Houston
country: United States
facility: Pd0053 50113
state: Texas
city: San Antonio
country: United States
facility: Pd0053 50400
state: Texas
city: Burlington
country: United States
facility: Pd0053 50107
state: Vermont
city: Charlottesville
country: United States
facility: Pd0053 50542
state: Virginia
city: Fairfax
country: United States
facility: Pd0053 50410
state: Virginia
city: Virginia Beach
country: United States
facility: Pd0053 50534
state: Virginia
city: Kirkland
country: United States
facility: Pd0053 50292
state: Washington
city: Spokane
country: United States
facility: Pd0053 50419
state: Washington
city: Crab Orchard
country: United States
facility: Pd0053 50402
state: West Virginia
city: Calgary
country: Canada
facility: Pd0053 50374
city: Kelowna
country: Canada
facility: Pd0053 50390
city: Ottawa
country: Canada
facility: Pd0053 50387
city: Toronto
country: Canada
facility: Pd0053 50389
city: Amiens
country: France
facility: Pd0053 40197
city: Bordeaux
country: France
facility: Pd0053 40527
city: Créteil
country: France
facility: Pd0053 40424
city: Lille
country: France
facility: Pd0053 40526
city: Marseille
country: France
facility: Pd0053 40130
city: Nantes
country: France
facility: Pd0053 40635
city: Nimes
country: France
facility: Pd0053 40524
city: Paris
country: France
facility: Pd0053 40525
city: Strasbourg
country: France
facility: Pd0053 40131
city: Toulouse Cedex 09
country: France
facility: Pd0053 40528
city: Berlin
country: Germany
facility: Pd0053 40515
city: Bonn
country: Germany
facility: Pd0053 40138
city: Dresden
country: Germany
facility: Pd0053 40530
city: Erbach
country: Germany
facility: Pd0053 40711
city: Erlangen
country: Germany
facility: Pd0053 40023
city: Essen
country: Germany
facility: Pd0053 40710
city: Haag in Oberbayern
country: Germany
facility: Pd0053 40532
city: Hannover
country: Germany
facility: Pd0053 40024
city: Kiel
country: Germany
facility: Pd0053 40249
city: Mainz
country: Germany
facility: Pd0053 40174
city: Marburg
country: Germany
facility: Pd0053 40529
city: Regensburg
country: Germany
facility: Pd0053 40531
city: Brescia
country: Italy
facility: Pd0053 40555
city: Padova
country: Italy
facility: Pd0053 40533
city: Roma
country: Italy
facility: Pd0053 40257
city: Roma
country: Italy
facility: Pd0053 40534
city: Roma
country: Italy
facility: Pd0053 40697
city: Nijmegen
country: Netherlands
facility: Pd0053 40359
city: Bydgoszcz
country: Poland
facility: Pd0053 40694
city: Jelenia Gora
country: Poland
facility: Pd0053 40719
city: Katowice
country: Poland
facility: Pd0053 40539
city: Krakow
country: Poland
facility: Pd0053 40538
city: Krakow
country: Poland
facility: Pd0053 40696
city: Lodz
country: Poland
facility: Pd0053 40700
city: Lublin
country: Poland
facility: Pd0053 40702
city: Oswiecim
country: Poland
facility: Pd0053 40535
city: Warszawa
country: Poland
facility: Pd0053 40536
city: Warszawa
country: Poland
facility: Pd0053 40699
city: Warszawa
country: Poland
facility: Pd0053 40705
city: A Coruña
country: Spain
facility: Pd0053 40045
city: Barcelona
country: Spain
facility: Pd0053 40159
city: Barcelona
country: Spain
facility: Pd0053 40267
city: Cordoba
country: Spain
facility: Pd0053 40046
city: Madrid
country: Spain
facility: Pd0053 40540
city: Móstoles
country: Spain
facility: Pd0053 40542
city: Pamplona
country: Spain
facility: Pd0053 40352
city: San Sebastián
country: Spain
facility: Pd0053 40541
city: Sevilla
country: Spain
facility: Pd0053 40049
city: London
country: United Kingdom
facility: Pd0053 40175
city: London
country: United Kingdom
facility: Pd0053 40543
city: London
country: United Kingdom
facility: Pd0053 40698
city: Motherwell
country: United Kingdom
facility: Pd0053 40544
city: Newcastle Upon Tyne
country: United Kingdom
facility: Pd0053 40306
city: Plymouth
country: United Kingdom
facility: Pd0053 40457
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References: