A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease

Early-stage Parkinson's Disease Clinical Trial

— ORCHESTRA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04658186
• Other study ID #: PD0053
• Secondary ID: 2020-003265-19
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 30, 2020
• Est. completion date: October 11, 2024

Study information

• Verified date: June 2024
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 496
• Est. completion date: October 11, 2024
• Est. primary completion date: October 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Early-stage Parkinson's Disease
• Parkinson Disease

Intervention

Drug:
• UCB0599
Drug: UCB0599 Pharmaceutical form: Granules in capsules Route of administration: Oral use Participants will receive UCB0599 in a pre-specified sequence during the Treatment Period.
• Placebo
Drug: Placebo Pharmaceutical form: Capsules Route of administration: Oral use Participants will receive Placebo in a pre-specified sequence during the Treatment Period.

Locations

Country	Name	City	State
Canada	Pd0053 50374	Calgary
Canada	Pd0053 50390	Kelowna
Canada	Pd0053 50387	Ottawa
Canada	Pd0053 50389	Toronto
France	Pd0053 40197	Amiens
France	Pd0053 40527	Bordeaux
France	Pd0053 40424	Créteil
France	Pd0053 40526	Lille
France	Pd0053 40130	Marseille
France	Pd0053 40635	Nantes
France	Pd0053 40524	Nimes
France	Pd0053 40525	Paris
France	Pd0053 40131	Strasbourg
France	Pd0053 40528	Toulouse Cedex 09
Germany	Pd0053 40515	Berlin
Germany	Pd0053 40138	Bonn
Germany	Pd0053 40530	Dresden
Germany	Pd0053 40711	Erbach
Germany	Pd0053 40023	Erlangen
Germany	Pd0053 40710	Essen
Germany	Pd0053 40532	Haag in Oberbayern
Germany	Pd0053 40024	Hanover
Germany	Pd0053 40249	Kiel
Germany	Pd0053 40174	Mainz
Germany	Pd0053 40529	Marburg
Germany	Pd0053 40531	Regensburg
Italy	Pd0053 40555	Brescia
Italy	Pd0053 40533	Padova
Italy	Pd0053 40257	Roma
Italy	Pd0053 40534	Roma
Italy	Pd0053 40697	Roma
Netherlands	Pd0053 40359	Nijmegen
Poland	Pd0053 40694	Bydgoszcz
Poland	Pd0053 40719	Jelenia Gora
Poland	Pd0053 40539	Katowice
Poland	Pd0053 40538	Krakow
Poland	Pd0053 40696	Krakow
Poland	Pd0053 40700	Lodz
Poland	Pd0053 40702	Lublin
Poland	Pd0053 40535	Oswiecim
Poland	Pd0053 40536	Warszawa
Poland	Pd0053 40699	Warszawa
Poland	Pd0053 40705	Warszawa
Spain	Pd0053 40045	A Coruña
Spain	Pd0053 40159	Barcelona
Spain	Pd0053 40267	Barcelona
Spain	Pd0053 40046	Cordoba
Spain	Pd0053 40540	Madrid
Spain	Pd0053 40542	Móstoles
Spain	Pd0053 40352	Pamplona
Spain	Pd0053 40541	San Sebastián
Spain	Pd0053 40049	Sevilla
United Kingdom	Pd0053 40175	London
United Kingdom	Pd0053 40543	London
United Kingdom	Pd0053 40698	London
United Kingdom	Pd0053 40544	Motherwell
United Kingdom	Pd0053 40306	Newcastle Upon Tyne
United Kingdom	Pd0053 40457	Plymouth
United States	Pd0053 50544	Augusta	Georgia
United States	Pd0053 50529	Baltimore	Maryland
United States	Pd0053 50547	Baltimore	Maryland
United States	Pd0053 50140	Birmingham	Alabama
United States	Pd0053 50396	Boca Raton	Florida
United States	Pd0053 50243	Boston	Massachusetts
United States	Pd0053 50524	Bradenton	Florida
United States	Pd0053 50107	Burlington	Vermont
United States	Pd0053 50084	Charleston	South Carolina
United States	Pd0053 50542	Charlottesville	Virginia
United States	Pd0053 50310	Chicago	Illinois
United States	Pd0053 50401	Chicago	Illinois
United States	Pd0053 50311	Cleveland	Ohio
United States	Pd0053 50372	Cleveland	Ohio
United States	Pd0053 50255	Columbus	Ohio
United States	Pd0053 50402	Crab Orchard	West Virginia
United States	Pd0053 50392	Danbury	Connecticut
United States	Pd0053 50531	Englewood	Colorado
United States	Pd0053 50410	Fairfax	Virginia
United States	Pd0053 50538	Farmington	Connecticut
United States	Pd0053 50386	Farmington Hills	Michigan
United States	Pd0053 50519	Fountain Valley	California
United States	Pd0053 50385	Fresno	California
United States	Pd0053 50113	Houston	Texas
United States	Pd0053 50525	Houston	Texas
United States	Pd0053 50549	Iowa City	Iowa
United States	Pd0053 50074	Kansas City	Kansas
United States	Pd0053 50292	Kirkland	Washington
United States	Pd0053 50532	Knoxville	Tennessee
United States	Pd0053 50416	La Jolla	California
United States	Pd0053 50397	Las Vegas	Nevada
United States	Pd0053 50121	Lexington	Kentucky
United States	Pd0053 50539	Little Rock	Arkansas
United States	Pd0053 50118	Los Angeles	California
United States	Pd0053 50543	Memphis	Tennessee
United States	Pd0053 50199	Miami	Florida
United States	Pd0053 50299	New Brunswick	New Jersey
United States	Pd0053 50395	New Orleans	Louisiana
United States	Pd0053 50077	New York	New York
United States	Pd0053 50119	New York	New York
United States	Pd0053 50521	New York	New York
United States	Pd0053 50526	Philadelphia	Pennsylvania
United States	Pd0053 50081	Phoenix	Arizona
United States	Pd0053 50506	Phoenix	Arizona
United States	Pd0053 50510	Portland	Oregon
United States	Pd0053 50536	Saint Paul	Minnesota
United States	Pd0053 50400	San Antonio	Texas
United States	Pd0053 50419	Spokane	Washington
United States	Pd0053 50530	Stony Brook	New York
United States	Pd0053 50394	Tampa	Florida
United States	Pd0053 50527	Toledo	Ohio
United States	Pd0053 50391	Tucson	Arizona
United States	Pd0053 50398	Tulsa	Oklahoma
United States	Pd0053 50534	Virginia Beach	Virginia
United States	Pd0053 50535	Williamsville	New York
United States	Pd0053 50399	Winfield	Illinois
United States	Pd0053 50546	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
UCB Biopharma SRL

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III sum score	Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I-III includes several items assessing motor and non-motor signs and symptoms including cognitive impairment, sleep problems, speech, facial expression etc. Each of the items in the UPDRS parts is measured on a scale of 0 to 4, where 0 is normal and 4 (higher score) represents severe abnormalities/worse outcome. The scores from all 3 parts will be added together in which higher scores indicate worse disease.	From Baseline up to 18 Months
Secondary	MDS-UPDRS Part III subscale	Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III includes motor items assessing speech, facial expression, rigidity, finger tapping, hand movements, pronation supination movements of hands, toe tapping, leg agility, arising from chair, gait, freezing of gait, postural stability, posture, global spontaneity of movement (body bradykinesia), postural tremor of the hands, kinetic tremor of the hands, rest tremor amplitude, and constancy of rest tremor. Each of the items in the UPDRS is measured on a scale of 0 to 4, where 0 is normal and 4 (higher score) represents severe abnormalities/worse outcome.	From Baseline up to 18 Months
Secondary	MDS-UPDRS Part III early-stage Parkinson's disease (ePD) subscore on selected items	Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III includes motor items assessing speech, facial expression, rigidity, finger tapping, hand movements, pronation supination movements of hands, toe tapping, leg agility, arising from chair, gait, freezing of gait, postural stability, posture, global spontaneity of movement (body bradykinesia), postural tremor of the hands, kinetic tremor of the hands, rest tremor amplitude, and constancy of rest tremor. Each of the items in the UPDRS is measured on a scale of 0 to 4, where 0 is normal and 4 (higher score) represents severe abnormalities/worse outcome. The ePD subscore targets the early-stage PD population using a subset of items from the MDS-UPDRS Part III subscale.	From Baseline up to 18 Months
Secondary	MDS-UPDRS Part II subscale	Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II includes motor items assessing speech, saliva and drooling, chewing and swallowing, eating tasks (cutting food and handling utensils), dressing, hygiene, handwriting, doing hobbies and other activities, turning in bed, tremor, getting out of bed, a car or a deep chair, walking and balance, and freezing. Each of the items in the UPDRS is measured on a scale of 0 to 4, where 0 is normal and 4 (higher score) represents severe abnormalities/worse outcome.	From Baseline up to 18 Months
Secondary	MDS-UPDRS Part I subscale	Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I includes several non-motor aspects of experiences of daily living including cognitive impairment, hallucinations and psychosis, depressed mood, anxious mood, apathy, features of dopamine dysregulation syndrome during part 1A and sleep problems, daytime sleepiness, pain and other sensation, urinary problems, constipation problems, lightheadedness on standing, and fatigue during Part 1B. Each of the items in the UPDRS is measured on a scale of 0 to 4, where 0 is normal and 4 (higher score) represents severe abnormalities/worse outcome.	From Baseline up to 18 Months
Secondary	Emerging symptoms as measured by MDS-UPDRS Part II	The participant is considered to have an emerging symptom for the item, if the change from Baseline for the item is greater than 0 for 2 consecutive visits. The magnitude of change from Baseline will not be considered to determine the emerging symptom. Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II includes motor items assessing speech, saliva and drooling, chewing and swallowing, eating tasks (cutting food and handling utensils), dressing, hygiene, handwriting, doing hobbies and other activities, turning in bed, tremor, getting out of bed, a car or a deep chair, walking and balance, and freezing. Each of the items in the UPDRS is measured on a scale of 0 to 4, where 0 is normal and 4 (higher score) represents severe abnormalities/worse outcome.	From Baseline up to 18 Months
Secondary	Time to worsening of the disease as measured by MDS-UPDRS Part III	Time to worsening of the disease on the MDS-UPDRS III scale as defined by a 5 point increase in MDS-UPDRS III, within the 18-month period.	From Baseline up to 18 Months
Secondary	Montreal Cognitive Assessment (MoCA)	The Montreal Cognitive Assessment (MoCA) assesses different cognitive domains (visuospatial/executive, naming, memory, attention, language, abstraction, delayed recall, and orientation). Participants are assessed on a 30-point scale. A score of 26 or above is considered normal, a lower score indicate cognitive impairment.	From Screening up to 18 Months
Secondary	Change in Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) mean striatum specific binding ratios (SBR)	The change from baseline (screening) in mean striatum specific binding ratios (SBR) will be assessed by Dopamine Transporter Imaging with Single Photon Emission Computed Tomography using 123I-Ioflupane as radiopharmaceutical.	From Screening up to 18 Months
Secondary	Time to start of symptomatic treatment (ST)	Time to start of symptomatic treatment (ST) within the 18-month period.	From Baseline up to 18 Months
Secondary	Symptomatic treatment (ST) intake	Number of participants on symptomatic treatment (ST) at 18 months	From Baseline up to 18 Months
Secondary	Incidence of treatment-emergent adverse events (TEAEs)	Adverse event: Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.	From Baseline up to 19 Months
Secondary	Incidence of serious adverse events (SAEs)	Serious adverse event: Death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.	From Screening up to 19 Months
Secondary	Incidence of TEAEs leading to participant withdrawal	Adverse event: Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.	From Baseline up to 19 Months