A Randomized, Placebo-controlled, Double-blind, Phase 2a Study to Evaluate the Clinical Efficacy, Safety, Tolerability, and Biomarker Effects of 2 Dose Levels of GT-02287 in Participants With Early Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 111
- 主要终点
- Change from Baseline to Week 48 in the sum of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score and Part III score [Efficacy]
研究概览
简要总结
The purpose of this study is to assess the efficacy, the safety, and the effect on biomarkers of 2 dose levels of oral GT-02287 over placebo after 48 weeks of treatment in treated and untreated participants with early PD.
详细描述
This is a 48-week, double-blind, randomized, placebo-controlled Phase 2a study testing two doses of oral GT-02287 in people with early Parkinson's disease (PD), both treated and untreated.
The study has three parts:
- Screening Period lasting up to 45 days
- Treatment Period lasting about 341 days
- Follow-up Period lasting up to 33 days Participants will have 7 onsite visits for efficacy, safety, tolerability, and biomarker assessments (Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, and a Follow-Up Visit at Week 52). In addition, there will be 5 additional visits for laboratory blood tests (Weeks 2, 16, 20, 30, and 42).
Approximately 111 participants will be randomized into three groups (high dose, low dose, placebo).
Participants can have idiopathic PD or be heterozygous for a pathogenic variant in the GBA1 gene. Participants who have other PD-associated genetic variants (e.g., leucine rich repeat kinase 2 [LRRK2]) are ineligible. All participants will be genotyped to determine their PD-associated genetic status before enrollment.
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
- 30 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to provide written informed consent and willing to comply with the requirements and restrictions of the study
- •Willing to undergo PD-related genetic testing and analysis
- •Any sex, ≥30 and ≤85 years of age
- •Body mass index of ≥18 and ≤40 kg/m2 and a body weight of at ≥55 kg and <120 kg at Screening
- •Diagnosis of PD based on MDS criteria
- •Within 5 years of PD diagnosis
- •Positive SAA in CSF at Baseline
- •Hoehn & Yahr 1-2.5, inclusive
- •Naïve to pharmacological treatment for PD with no initiation of dopaminergic treatment expected during the first 9 months of the study or on stable PD medication for ≥3 months prior to Screening, including ≥4 weeks at the same dose(s) immediately before Screening with no changes to dose(s), or medication(s) expected during the first 9 months of the study
- •Not pregnant or breastfeeding
- •If participant is either of childbearing potential or produces potentially viable sperm, participant must agree to use 2 forms of contraception (barrier method and a second highly effective form of birth control/contraception, as defined in the protocol) if engaging in potentially reproductive intercourse (with a partner who produces potentially viable sperm or is of childbearing potential, respectively)
- •Agreeing not to participate in another investigational study while taking part in this study
排除标准
- •Other neurological disorders, including but not limited to Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome, Huntington's disease, multiple system atrophy, dementia with Lewy bodies, secondary (e.g. drug-induced) parkinsonism, multiple sclerosis, or epilepsy
- •PD-associated LRRK2 pathogenic variant or other PD-associated genetic mutations other than GBA1
- •Severe motor fluctuations and/or disabling dyskinesias based on the investigator's clinical assessment
- •Deep-brain stimulation
- •Hallucinations, delusions, or other psychotic symptoms requiring antipsychotic medication Use of dopamine antagonists (antipsychotics) or anticholinergic medications
- •Dementia by clinical diagnosis and/or a MoCA score of ≤20 and/or a history of behavioral impairment
- •Hypersensitivity to GT 02287 or any of its excipients
- •Concomitant medications including drugs metabolized primarily by CYP3A4 that have a narrow therapeutic window, substrates of BCRP that have a narrow therapeutic window, strong or moderate inhibitors or strong inducers of CYP3A4 that could affect the metabolism and plasma levels of GT 02287, including herbal supplements and certain foods.
- •Concomitant disease including, but not limited to cardiovascular conditions, diabetes, autoimmune disease, cancer, active infectious disease, psychotic disorders and symptoms, depressive symptoms, drug and/or alcohol misuse as defined in the protocol
- •Clinically significant abnormalities in laboratory test
- •Contraindications to lumbar puncture (LP) including current treatment with anticoagulants or any other contraindications that might preclude safe completion of the LP
- •Blood donation >500 mL within 3 months
- •Malabsorption or relevant disorder which may impact the absorption of GT-02287
- •Participation in any interventional clinical study within 3 months or 5 half-lives, whichever is longer, prior to Screening
研究组 & 干预措施
Low Dose GT-02287
GT-02287 400 or 600 mg/day
干预措施: Low Dose GT-02287 (Drug)
High Dose GT-02287
GT-02287 800 or 1000 mg/day
干预措施: High Dose GT-02287 (Drug)
Placebo
Magnesium aluminometasilicate (MAS)
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline to Week 48 in the sum of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score and Part III score [Efficacy]
时间窗: From baseline to Week 48
Change from Baseline to Week 48 in the sum of the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score and Part III score assessed in the practically defined OFF state. MDS-UPDRS is a multimodal scale assessing impairment and disability consisting of four parts. Part II assesses motor experiences of daily living (Range 0-52). It contains 13 questions which are to be rated by the patient and/or caregiver. Part III assesses the motor signs of PD and is rated by the investigator (Range 0-132). Part III contains 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. A higher score indicates more severe symptoms of PD.
次要结局
- Incidence of Treatment-Emergent Adverse Events [Safety and tolerability](From baseline to Week 48)
- Change from Baseline to Week 48 in the MDS-UPDRS Part II score [Effect on motor function](From baseline to Week 48)
- Change from Baseline to Week 48 in the MDS-UPDRS Part III score [Effect on motor function](From baseline to Week 48)
- Change from Baseline to Week 48 in the Timed Up and Go (TUG) test [Effect on motor function](From baseline to Week 48)
- Change from Baseline to Week 48 in the Parkinson's Disease Questionnaire 39 (PDQ-39) score [Effect on quality of life](From baseline to Week 48)
- Change from Baseline to Week 48 in the Schwab and England Activities of Daily Living (SEADL) scale [Effect on activities of daily living](From baseline to Week 48)
- Change from Baseline to Week 48 in the Patient Global Impression Scale - Severity (PGI-S)(From baseline to Week 48)
- Change from Baseline to Week 48 in the Clinical Global Impressions Scale - Severity (CGI-S)(From baseline to Week 48)