A Randomised, Double-Blind, Multi-centre, Active Treatment, Extension and Safety Study for Patients With Idiopathic Parkinson's Disease (PD) Who Previously Completed the CDNF/DDS Main Study HP-CD-CL-2002
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
研究概览
简要总结
This study is an extension to the HP-CD-CL-2002 clinical study. It evaluates the long-term safety and tolerability of CDNF in patients with Parkinson's disease when dosed directly into the brain using an implanted investigational drug delivery system (DDS). Long-term safety of the DDS is also being evaluated. All patients will receive monthly infusions of either mid- or high-dose of CDNF for a period of 6 months.
详细描述
A patient's participation in the study will last for six months and will include nine visits:
Screening (1 visit, same as HP-CD-CL-2002 End-of-Study visit) Dosing visits: CDNF (6 visits) DAT-PET (1 visit) End-of-study visit (1 visit)
Study examinations and assessments
- Physical examination: pulse rate, blood pressure, temperature, body weight and height, body mass index (BMI), neurological exam
- ECG (electrocardiography) and blood and urine tests
- Pregnancy tests for women of childbearing age
- Completion of a patient diary to record mobility and time asleep
- Parkinson's Kinetigraph (PKGTM) Data Logger: a watch-type movement recording device
- Questionnaires, rating scales and forms: quality of life, mood, memory, impulse control, mental health
- Assessment of the port and the skin around the port
- Cerebrospinal fluid sampling by lumbar puncture
- Magnetic resonance imaging (MRI)
- Positron emission tomography scans (PET)
For more information: https://treater.eu/clinical-study/
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)
盲法说明
Double-Blind
入排标准
- 年龄范围
- 35 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completion of 6 months treatment period in the Main study (HP-CD-CL-2002) including End-of-Study assessment
- •Negative pregnancy test at study entry for females of childbearing potential. Willingness of using a highly effective form of contraception until 30 days after end of study. Males: willingness to use condom and not to donate sperm for 3 months following DAT-PET. Willingness of female partners of male study participants to use highly effective form of contraception until 30 days after their male partner's end of the study.
- •At least one functioning catheter in each putamen
- •Provision of informed consent
排除标准
- •Drug-resistant rest tremor, severe dyskinesia or severe head tremor, which could interfere with treatment infusions
- •Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsy, CSF shunt or other implanted central nervous system device
- •Changes in pathology which give rise to safety concern such as sequelae from catheter implantation, clinically significant intracerebral trauma, oedema, haemorrhage, or infection
- •Current psychosis requiring therapy
- •Presence of clinically significant impulse control disorder by a positive screen on the QUIP-RS questionnaire score >20, or, presence of dopamine dysregulation syndrome
- •An unresolved intolerable adverse event or adverse device event in study HP-CD-CL-2002, which is not expected to resolve or cease to an acceptable level of intensity within reasonable time
- •Medical conditions, which might impair outcome measure assessments or safety measures
- •Impaired renal function
- •Concomitant treatment with neuroleptics or antipsychotic medication prescribed for treatment of current psychosis, central dopamine blockers or tricyclic antidepressants
研究组 & 干预措施
CDNF mid-dose (400 micrograms)
Patients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to mid-dose (400 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen.
干预措施: Cerebral Dopamine Neurotrophic Factor (Drug)
CDNF mid-dose (400 micrograms)
Patients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to mid-dose (400 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen.
干预措施: Renishaw Drug Delivery System (Device)
CDNF high-dose (1200 micrograms)
Patients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to high-dose (1200 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen.
干预措施: Cerebral Dopamine Neurotrophic Factor (Drug)
CDNF high-dose (1200 micrograms)
Patients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to high-dose (1200 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen.
干预措施: Renishaw Drug Delivery System (Device)
结局指标
主要结局
Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
时间窗: Week 40 to Week 65
Total number, causality and severity of adverse events at any time during the study period
Changes in physical examination: clinical standard neurological examination
时间窗: Week 40 and Week 65
A clinical standard neurological examination by study investigator. Changes in motor function, sensory function, cranial nerve function (visual fields), cortical functions and reflexes are followed in the examination, scored as normal - abnormal without clinical relevance - abnormal with clinical relevance
Changes in vital signs: blood pressure [safety-tolerability]
时间窗: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)
Changes in vital signs: body temperature [safety-tolerability]
时间窗: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in body temperature during the study (in degrees celsius)
Changes in vital signs: body weight [safety-tolerability]
时间窗: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in body weight during the study (in kilograms)
Changes in clinical laboratory safety screen: clinical chemistry [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for clinical chemistry (Na, K, Urea, creatinine, creatine kinase, Ca, Bilirubin, IgG, Albumin, ALP, ALT, AST)
Changes in clinical laboratory safety screen: haematology - hemoglobin [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: hemoglobin (g/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: haematology - hematocrit [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: hematocrit (%, ratio of red blood cell volume to total blood volume). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Change in Electrocardiogram (ECG): Ventricular rate, PR interval, qRS duration, QT, QTc [safety-tolerability]
时间窗: Week 40, Week 53 and Week 65
Changes in electrical activity of heartbeat measured by electrocardiogram: Ventricular rate (bpm), PR interval (msec), QRS duration (msec), QT (msec), QTc (msec)
Change in Beck Depression Inventory (BDI) score [safety-tolerability]
时间窗: Week 40, Week 53 and Week 65
Assessment of change in depression using Beck Depression Inventory (BDI) score: Sadness: Pessimism; Past Failure; Loss of pleasure; Guilty feelings; Punishment Feelings; Self-dislike; Self-criticalness;Suicidal thoughts or wishes; Crying; Agitation; Loss of interest; Indecisiveness;Worthlessness; Loss of energy; Changes in sleeping pattern; Irritability; Changes in appetite; Concentration difficulty; Tiredness or fatique; Loss of interest in sex. Rated on a 4-point scale ranging from 0 to 3 based on severity of each item (0=low intensity; 3=highest intensity). The maximum total score is 63.
Changes in vital signs: pulse rate [safety-tolerability]
时间窗: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in pulse rate during the study (in beats per minute)
Change in Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [safety-tolerability]
时间窗: Week 40, Week 53 and Week 65
Assessment of changes in impulsive-compulsive disorders using QUIP_RS. Questions scored 0-4 (0=never; 4=very often) on gambling, sex, buying, eating, performing tasks/hobbies, repeating simple activities, and taking Parkinson's disease medication. Total QUIP-RS Score 0-112
Change in Montreal cognitive assessment (MoCA) [safety-tolerability]
时间窗: Week 40, Week 53 and Week 65
Assessment of change in cognitive domains using MoCA test: attention and, concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points; a score of 26 or above is considered normal.
Changes in clinical laboratory safety screen: mean cell hemoglobin of RBC (MHC) [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: MCH (pg). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: INR (standardized prothrombin time) to determine the effects of oral anticoagulants on the clotting system. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Formation of anti-CDNF antibodies [safety-tolerability]
时间窗: Weeks 40, 45, 49, 53, 57, 61, and 65
Formation and change in anti-CDNF antibody concentration (in ng/ml).
Device related occurrence of adverse device effects [safety-tolerability]
时间窗: Week 40 to Week 65
Occurrence of adverse device effects (ADE) at any time of the study period, for either the whole system or the individual sub systems (guide tubes/catheters, subcutaneous components, port), serious adverse device effect (SADE) including long term effects, neurological deficit (seizures), infection (local to components, in CNS), severe skin breakdown or necrosis requiring component removal life threatening or major (requiring intervention) intracerebral haemorrhage.
Changes in physical examination: anatomic findings [safety-tolerability]
时间窗: Week 40 and Week 65
Changes in anatomic findings found in physical examination of the following body systems: general inspection/upper extremities; head, eyes, ears, nose, throat, and superficial cervial lymph notes; neck, shoulders, back; chest and lungs; cardiovascular; abdomen; lower extremities
Changes in vital signs: body mass index (BMI) [safety-tolerability]
时间窗: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in body mass index during the study (in kg/m\^2)
Changes in clinical laboratory safety screen: haematology - red blood cell (RBC) count [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: RBC count (10E12/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: mean cell volume (MCV) of red blood cells [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: MCV of red blood cells (fL). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: aPTT (sec) . Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: urinanalysis [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for urinanalysis (blood/erythrocytes, glucose, ketones, leukocytes, nitrites, pH, protein) studied by dipstick and scored 0-3. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: Platelet count [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: Platelet count (10E9/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: white blood cell (WBC) counts [safety-tolerability]
时间窗: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: Cell counts (10E9/L) for total WBC, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
次要结局
- Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy](Week 40, Week 53 and Week 65)
- Change in TUG (Timed Up and Go) test [efficacy](Week 40, Week 53 and Week 65)
- Change in UPDRS Total score (Part I-IV) [efficacy](Week 40, Week 53 and Week 65)
- Change in home diary score [efficacy](Weeks 40, 45, 49, 49, 53, 57, 61 and 65)
- Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy](Week 40, Week 53 and Week 65)
- Change in CGI-I (Clinical Global Impression - Improvement) scale [efficacy](Weeks 40, 45, 49, 53, 57, 61 and 65)
- Occurrence of blockage [performance assessment](Week 41, 45, 49, 53, 57 and Week 61)
- Stability of transcutaneous port: Inability to start infusion due to connectivity problem in Drug Delivery System(Week 41 to Week 61)