A 18-month Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Oral UCB0599 in Study Participants With Early-stage Parkinson's Disease (ORCHESTRA)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04658186 |
|
Recruitment Status :
Active, not recruiting
First Posted : December 8, 2020
Last Update Posted : May 13, 2024
|
Sponsor:
UCB Biopharma SRL
Information provided by (Responsible Party):
UCB Pharma ( UCB Biopharma SRL )
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Early-stage Parkinson's Disease | Drug: UCB0599 Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 496 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | December 30, 2020 |
| Estimated Primary Completion Date : | October 7, 2024 |
| Estimated Study Completion Date : | November 5, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Parkinson disease
MedlinePlus related topics:
Parkinson's Disease
| Arm | Intervention/treatment |
|---|---|
|
Experimental: UCB0599 High Dose Arm
Participants will be randomized to receive a predefined high dosage of UCB0599 during the Treatment Period.
|
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 Comparator: Placebo Arm
Participants will be randomized to receive a predefined dosage of Placebo during the Treatment Period.
|
Drug: Placebo
Drug: Placebo Pharmaceutical form: Capsules Route of administration: Oral use Participants will receive Placebo in a pre-specified sequence during the Treatment Period. |
|
Experimental: UCB0599 Low Dose Arm
Participants will be randomized to receive a predefined low dosage of UCB0599 during the Treatment Period.
|
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. |
Primary Outcome Measures :
- Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III sum score [ Time Frame: From Baseline up to 18 Months ]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.
Secondary Outcome Measures :
- MDS-UPDRS Part III subscale [ Time Frame: From Baseline up to 18 Months ]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.
- MDS-UPDRS Part III early-stage Parkinson's disease (ePD) subscore on selected items [ Time Frame: From Baseline up to 18 Months ]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.
- MDS-UPDRS Part II subscale [ Time Frame: From Baseline up to 18 Months ]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.
- MDS-UPDRS Part I subscale [ Time Frame: From Baseline up to 18 Months ]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.
- Emerging symptoms as measured by MDS-UPDRS Part II [ Time Frame: From Baseline up to 18 Months ]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.
- Time to worsening of the disease as measured by MDS-UPDRS Part III [ Time Frame: From Baseline up to 18 Months ]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.
- Montreal Cognitive Assessment (MoCA) [ Time Frame: From Screening up to 18 Months ]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.
- Change in Dopamine Transporter Imaging with Single Photon Emission Computed Tomography (DaT-SPECT) mean striatum specific binding ratios (SBR) [ Time Frame: From Screening up to 18 Months ]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.
- Time to start of symptomatic treatment (ST) [ Time Frame: From Baseline up to 18 Months ]Time to start of symptomatic treatment (ST) within the 18-month period.
- Symptomatic treatment (ST) intake [ Time Frame: From Baseline up to 18 Months ]Number of participants on symptomatic treatment (ST) at 18 months
- Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: From Baseline up to 19 Months ]Adverse event: Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
- Incidence of serious adverse events (SAEs) [ Time Frame: From Screening up to 19 Months ]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.
- Incidence of TEAEs leading to participant withdrawal [ Time Frame: From Baseline up to 19 Months ]Adverse event: Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 40 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04658186
Locations
Show 115 study locations
Sponsors and Collaborators
UCB Biopharma SRL
Investigators
| Study Director: | UCB Cares | 001 844 599 2273 |
| Responsible Party: | UCB Biopharma SRL |
| ClinicalTrials.gov Identifier: | NCT04658186 |
| Other Study ID Numbers: |
PD0053 2020-003265-19 ( EudraCT Number ) |
| First Posted: | December 8, 2020 Key Record Dates |
| Last Update Posted: | May 13, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion. |
| Access Criteria: | Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. |
| URL: | https://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by UCB Pharma ( UCB Biopharma SRL ):
|
Early-stage parkinson's disease UCB0599 Phase 2 Early-stage PD |
Additional relevant MeSH terms:
|
Parkinson Disease Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Movement Disorders Synucleinopathies Neurodegenerative Diseases |