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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 496
- 试验地点
- 115
- 主要终点
- Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Day 0
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
UCB0599 High Dose Arm
Participants will be randomized to receive a predefined high dosage of UCB0599 during the Treatment Period.
干预措施: UCB0599 (Drug)
Placebo Arm
Participants will be randomized to receive a predefined dosage of Placebo during the Treatment Period.
干预措施: Placebo (Drug)
UCB0599 Low Dose Arm
Participants will be randomized to receive a predefined low dosage of UCB0599 during the Treatment Period.
干预措施: UCB0599 (Drug)
结局指标
主要结局
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Day 0
时间窗: Day 0
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 2
时间窗: Month 2
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 4
时间窗: Month 4
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 6
时间窗: Month 6
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 16
时间窗: Month 16
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 8
时间窗: Month 8
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 10
时间窗: Month 10
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 12
时间窗: Month 12
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 14
时间窗: Month 14
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I-III Sum Score at Month 18
时间窗: Month 18
MDS-UPDRS is a multimodal scale. Part I assessed non-motor experiences of daily living and has 2 components (0-52 possible points). Part IA contains 6 questions and is assessed by the examiner (0-24 possible points). Part IB contains 7 questions on non-motor experiences of daily living completed by participant (0-28 possible points). Part II assessed motor experiences of daily living (0-52 possible points) and includes 13 questions completed by participant. Part III assessed motor signs of PD and was administered by rater (0-52 possible points). Part III contained 33 questions based on 18 items. For all questions of each part, numeric score response options linked to accepted clinical terms: 0 to 4, 0=Normal, 1=Slight, 2=Mild, 3=Moderate, 4=Severe. Total Score equals sum of Parts I, II, and III (Score: 0-236). Higher score = more severe PD symptoms.
次要结局
- MDS-UPDRS Part III Subscale(Day 0, Months 2, 4, 6, 8, 10, 12, 14, 16, 18)
- MDS-UPDRS Part III Early-stage Parkinson's Disease (ePD) Subscore on Selected Items(Day 0, Months 2, 4, 6, 8, 10, 12, 14, 16, 18)
- MDS-UPDRS Part II Subscale(Day 0, Months 2, 4, 6, 8, 10, 12, 14, 16, 18)
- MDS-UPDRS Part I Subscale(Day 0, Months 2, 4, 6, 8, 10, 12, 14, 16, 18)
- Emerging Symptoms in Participants as Measured by MDS-UPDRS Part II(Baseline to Month 18)
- Time to Worsening of the Disease as Measured by MDS-UPDRS Part III(Baseline to Month 18)
- Montreal Cognitive Assessment (MoCA)(Screening, Month 18)
- Change From Screening in Dopamine Transporter Imaging With Single Photon Emission Computed Tomography (DaT-SPECT) Mean Striatum Specific Binding Ratios (SBR)(Screening, Months 12 and 18)
- Time to Start of Symptomatic Treatment (ST)(Baseline to Month 18)
- Symptomatic Treatment (ST) Intake(Month 18)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)(From Baseline up to 30 days of safety follow-up after the last dose of the study drug (up to 19 months))
- Percentage of Participants With Serious TEAEs(From Baseline up to 30 days of safety follow-up after the last dose of the study drug (up to 19 months))
- Percentage of Participants With TEAEs Leading to Participant Withdrawal(From Baseline up to 30 days of safety follow-up after the last dose of the study drug (up to 19 months))