A Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of UCB0022 in Study Participants With Advanced Parkinson's Disease

Study Overview
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Brief Summary
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The primary purpose of this study is to demonstrate the superiority of UCB0022 as an adjunctive treatment to stable dose of standard-of-care (SoC) (including at least levodopa therapy) over placebo with regard to motor fluctuations time spent in the OFF state (OFF time) in study participants with advanced Parkinson's Disease (PD).

Official Title
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A Multicenter Phase 2, Double-blind, Placebo-controlled, Randomized, Parallel-group Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of UCB0022 in Study Participants With Advanced Parkinson's Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Other: Placebo
* Drug: UCB0022


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participant must be 35 to 80 years of age (inclusive) at the time of signing the informed consent form (ICF) Study participant is diagnosed with Parkinson's disease (PD) (based on the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic criteria performed at the Screening Visit) and diagnosed ≥5 years before the Screening Visit (based on historical medical- information documented by the investigator) Study participant has significant daily motor fluctuations Study participant is able to complete a Hauser PD symptoms diary and differentiate between the ON and OFF states Study participant is responsive to levodopa and currently receiving treatment with oral daily doses of levodopa combination (levodopa/carbidopa or levodopa/benserazide) with or without oral adjunctive antiparkinsonian therapies (based on historical clinical data) Study participant has disease severity Stages I-III (modified Hoehn and Yahr staging) during ON state Study participant agrees to not post personal medical data or information related to the study on social media until study completion Study participant has body weight ≥45 kg and body mass index within 18 to 30 kg/m^2 (inclusive) Study participant may be male or female: A male study participant must agree to use contraception during the Treatment Period and for at least 2 weeks after the last dose of study treatment and refrain from donating sperm during this period A female study participant must not be a woman of childbearing potential (WOCBP) Exclusion Criteria: Study participant is diagnosed with any form of Parkinsonism other than idiopathic PD (eg, atypical or secondary Parkinsonism) Study participant is diagnosed with dementia or has important cognitive dysfunction, as determined by Montreal Cognitive Assessment (MoCA) <23 at screening Study participant has a history of neurosurgical intervention for PD (including DBS, thalamotomy, and experimental cell therapy or gene therapy) Participant has a severe peak dose or biphasic dyskinesia at screening, defined by Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) items 4.2 score 4 or as per investigator opinion Participant has a history of major depression or psychotic disorder or any other psychiatric condition within the past 5 years, that, as per investigator opinion, could jeopardize or would compromise the study participant's ability to participate in the study Study participant has a history of narrow angle glaucoma Study participant has a history of melanoma Study participant has current untreated hypertension Study participant has a history of hypertensive crisis and/or hypertensive encephalopathy, unless the underlying cause was unequivocally identified and has been removed Study participant has orthostatic hypotension requiring medication or a current history of clinically significant orthostatic hypotension as per the investigator's opinion (eg, recurrent orthostatic presyncope or syncope) Study participant has a history over the past 12 months or between the Screening and Baseline Visits of any clinically significant arrythmia, myocardial infarction, stroke, transient ischemic attack, moderate or severe congestive heart failure (either New York Heart Association Class III or IV or known ejection fraction <40%)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: UCB0022-Dose A<br>Study participants randomized to this arm will receive UCB0022 Dose A orally administered as tablet during the Treatment Period. | Drug: UCB0022<br>* Study participants will receive UCB0022 dose A or B orally administered as tablet at pre-specified time points during the Treatment Period.<br>|
| Experimental: UCB0022-Dose B<br>Study participants randomized to this arm will receive UCB0022 Dose B orally administered as tablet during the Treatment Period. | Drug: UCB0022<br>* Study participants will receive UCB0022 dose A or B orally administered as tablet at pre-specified time points during the Treatment Period.<br>|
| Placebo Comparator: Placebo<br>Study participants randomized to this arm will receive matching placebo orally administered as tablet during the Treatment Period. | Other: Placebo<br>* Study participants will receive placebo orally administered as tablet at pre-specified time points during the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Visit 9 (Day 70) in the average number of hours/day of OFF time, as assessed by the study participant-completed Hauser PD symptoms diary over 3 consecutive days | The Hauser Parkinson's disease (PD) symptoms diary is a study participant-completed diary that records the daily ON time and OFF time of study participants with PD with motor fluctuations and dyskinesia. | From Baseline (Day 1) to Visit 9 (Day 70) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 2 weeks after the final dose. | From Baseline (Day 1) to End of Safety Follow-up (up to Week 12) | 
| Incidence of treatment-emergent serious adverse events (SAEs) | A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical events Treatment-emergent AEs are defined as those AEs that have a start date on or following the first dose of investigational medicinal product (IMP). | From Baseline (Day 1) to End of Safety Follow-up (up to Week 12) | 
| Incidence of TEAEs leading to withdrawal from the study | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of IMP, whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. TEAEs are defined as AEs starting after the time of first IMP administration up to and including 2 weeks after the final dose. | From Baseline (Day 1) to End of Safety Follow-up (up to Week 12) | 
| Average Ctrough of UCB0022 and its active N-desmethyl-UCB0022 metabolite at Visit 9 (Day 70) | Ctrough: The predose observed plasma concentration (average, per visit) will be plotted and depicted graphically to assess trajectory to steady-state for parent and active metabolites. | at Visit 9 (Day 70) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson Disease, Phase 2, UCB0022, wearing-off, motor fluctuations