Phase IIa Study to Evaluate the Efficacy and Safety of Subcutaneous SR-Exenatide (PT320) in Patients With Early Parkinson's Disease
试验速览
- 阶段
- 2 期
- 入组人数
- 99
- 试验地点
- 5
- 主要终点
- Change of MDS-UPDRS part 3 score
研究概览
简要总结
This study is to evaluate the safety and efficacy of sustained release (SR)-Exenatide (PT320, Q1W and Q2W) in the treatment of patients with early Parkinson's disease (PD).
详细描述
This study is a multicenter, randomized, double-blind, placebo-controlled, parallel comparison, phase IIa clinical study to evaluate the efficacy and safety of sustained release (SR)-Exenatide (PT320) in the treatment of patients with early Parkinson's disease (PD).
Exenatide (GLP-1) has been approved by the Food and Drug Administration (FDA) to treat patients with Type 2 Diabetes (T2D) and obesity. In addition, several research groups have confirmed that Exenatide has beneficial aspects due to the neuroprotective effects in neuronal cells in patients with PD. Peptron has developed a sustained-release (SR)-Exenatide, (PT320, Q1W and Q2W), which has shown a higher Blood-Brain Barrier (BBB) penetration rate and better patient compliance.
Thus, the objective of this study is to evaluate the effect of PT320 on symptom improvement and the inhibition of disease progression in the treatment of patients with early Parkinson's disease. Also, pharmacokinetic analysis of PT320 in blood cerebrospinal fluid (CSF) and exosome analysis of biomarkers related to Exenatide will be being tested, as exploratory measurements.
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
- •Patient who is male or female aged 40-75 and is diagnosed with Parkinson's Disease (using Queen Square Brain Bank criteria)
- •Patient who is diagnosed of Parkinson's Disease less than 24 months prior to the screening
- •Patient who has a modified Hoehn and Yahr stage ≤
- •Patient who has been taking L-dopa stable-dose less than 600 mg/day or who has not previously taken any medication for the treatment of Parkinson's Disease from 4 weeks prior to the screening.
- •Patient who is able to inject an Investigational Product by himself/herself or a his/her guardian.
- •Patient or legally acceptable representative who signs the informed consent form voluntarily and is able to comply with all study procedures
排除标准
- •Patient who is diagnosed or suspected to have Parkinson-plus syndromes (e.g., Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Degeneration, Diffuse Lewy Body Disease, and etc.)
- •Patient who has a BMI < 18.5 at the screening
- •Patient who has known abnormalities on CT or MRI brain imaging that may have an impact on the protocol compliance and/or PET scan
- •Patient who has dementia with MoCA-K ≤ 22
- •Patient who has a history of severe heart failure (NYHA class III to IV), stroke, cerebral ischemic attack, or seizure within 1 year prior to screening; or a history myocardial infarction or unstable angina within 6 months prior to screening.
- •Patient who has severe liver disease or has AST or ALT level 3 times more than ULN at the screening
- •Patient who has clinically significant depression [> 18 of Korean Beck Depression Inventory II score (K-BDI-II)]
- •Patient who has a history of brain surgery for any treatment of Parkinson's disease
- •Patient who has participated in any clinical trials for the treatment of Parkinson's Disease within 3 months prior to screening
- •Patient who took exenatide within 90 days prior to randomization
- •Patient who has a history of gastroduodenal ulcer or gastroparesis within 3 months prior to administration of investigational product or is currently on medication for acute or chronic gastritis
- •Patient who has severe kidney function injury (creatinine clearance < 30 ml/min)
- •Patient who has a history of pancreatitis
- •Patient who has type 1 or type 2 diabetes or HbA1c ≥ 6.5% at screening
- •Patient who has a history or suspected to thyroid cancer or multiple endocrine adenomatosis
- •Patient who has known or suspected intolerance in PET scan or fluoropropyl-CIT (18F)
- •Woman childbearing potential who doesn't agree to use the medically acceptable methods of contraception* during this study and up to 24 weeks after the last injection of investigational product
- •*Medically acceptable methods of contraception: oral contraceptives, intrauterine contraceptive devices, vasectomy for male partner, barrier method [condom, spermicidal foam/gel/film/cream/suppository with sealed cap (diaphragm or cervix/bolt cap)].
- •Woman who is pregnant or breastfeeding
- •Patient who has a history of hypersensitivity reactions to any ingredients of investigational product
- •Patient who is not eligible for the study at the discretion of the investigator
研究组 & 干预措施
PT320 2.0mg Placebo
will be injected subcutaneously once a week for 48 weeks
干预措施: PT320 2.0mg Placebo (Drug)
PT320 2.0mg treatment 1
will be injected subcutaneously once a week for 48 weeks
干预措施: PT320 2.0 mg (Drug)
PT320 2.5mg treatment2
will be injected subcutaneously every two weeks for 48 weeks. (Actually, patients will be injected PT320 2.5 mg and placebo alternately once a week.)
干预措施: PT320 2.5 mg (Drug)
结局指标
主要结局
Change of MDS-UPDRS part 3 score
时间窗: 48 week
Change of MDS-UPDRS (Movement Disorder Society -Unified Parkinson's Disease Rating Scale ) part 3 score from baseline at 48 weeks. The MDS-UPDRS has four parts: Part I (non-motor experiences of daily living), Part II (motor experiences of daily living), Part III (motor examination) and Part IV (motor complications). The MDS-UPDRS consists of five measures, 0(normal) to 4(severe), according to each item, and is evaluated as the total score per part of Part 1 to 4. A 0 means there is no disability, and the higher the score, the more the disability is reflected.
次要结局
- MDS-UPDRS part 1, 2 and 4 scores(0, 24, 48 and 60 weeks)
- K-PDQ-39 score(0, 48 and 60 weeks)
- MoCA-K score(0, 24, 48 and 60 weeks)
- MDS-UPDRS part 3 score(0, 24 and 60 weeks)
- K-NMSS score(0, 24, 48 and 60 weeks)
- Change of the L-dopa dosage of subjects(0, 2, 4, 8, 12, 24, 36, 48 and 60 weeks)
- Each percentage of subjects and changing patterns in modified Hoehn and Yahr stage(0, 24, 48 and 60 weeks)
- SNBR (specific to non-specific binding ratio) confirmed by PET scan(0 and 48 weeks)