Back to resultsSafety of CDNF by Brain Infusion in Patients With Parkinson's Disease. Extension to HP-CD-CL-2002 Clinical Study
Primary Purpose
Parkinson Disease, Movement Disorders, Neuro-Degenerative Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Cerebral Dopamine Neurotrophic Factor
Renishaw Drug Delivery System
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinson, CDNF, Drug Delivery System, Intracerebral
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Sites / Locations
- Helsinki University Hospital
- Skåne University Hospital
- Karolinska University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
CDNF mid-dose (400 micrograms)
CDNF high-dose (1200 micrograms)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
Total number, causality and severity of adverse events at any time during the study period
Change in Electrocardiogram (ECG): Ventricular rate, PR interval, qRS duration, QT, QTc [safety-tolerability]
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]
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.
Change in Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [safety-tolerability]
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]
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 physical examination: anatomic findings [safety-tolerability]
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 physical examination: clinical standard neurological examination
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]
Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)
Changes in vital signs: pulse rate [safety-tolerability]
Changes in pulse rate during the study (in beats per minute)
Changes in vital signs: body temperature [safety-tolerability]
Changes in body temperature during the study (in degrees celsius)
Changes in vital signs: body weight [safety-tolerability]
Changes in body weight during the study (in kilograms)
Changes in vital signs: body mass index (BMI) [safety-tolerability]
Changes in body mass index during the study (in kg/m^2)
Changes in clinical laboratory safety screen: clinical chemistry [safety-tolerability]
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]
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]
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".
Changes in clinical laboratory safety screen: haematology - red blood cell (RBC) count [safety-tolerability]
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]
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: mean cell hemoglobin of RBC (MHC) [safety-tolerability]
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: Platelet count [safety-tolerability]
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]
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".
Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [safety-tolerability]
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: International Normalized Ratio (INR) [safety-tolerability]
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".
Changes in clinical laboratory safety screen: urinanalysis [safety-tolerability]
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".
Formation of anti-CDNF antibodies [safety-tolerability]
Formation and change in anti-CDNF antibody concentration (in ng/ml).
Device related occurrence of adverse device effects [safety-tolerability]
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.
Secondary Outcome Measures
Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy]
Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores (each scored 0-4; 0=none, 4=severe): Speech; facial expression; tremor a rest; Tremor of hands; rigidity; firger taps; hand movelents; alternating movement of hands; leg agility; rising from chair; posture; gait; postural stability; body bradykinesia and hypokinesia. The total score, the sum of scores received from 27 assessments, is 0 - 108
Change in TUG (Timed Up and Go) test [efficacy]
Changes in mobility assessed by TUG test (in minutes and seconds).
Change in UPDRS Total score (Part I-IV) [efficacy]
Change in severity of PD non-motor and motor symptoms assessed by UPDRS Part I-IV total scores (Parts I, II and IV in ON-state; Part III in OFF-state): Part 1 (scored 0-16) Mentation, behaviour and mood. Part 2 (scored 0-52) Activities of daily living. Part 3 (scored 0-108) Motor examination. Part 4 (scored 0-23) Complications of therapy. The total score is 0-199 (0=totally healthy; 199=worst possible).
Change in home diary score [efficacy]
Change in functional status of the patient's dyskinesias assessed by home diary score for three-day period. Each half hour is scored: sleep, OFF, ON without dyskinesias, ON with non-troublesome dyskinesias, ON with troublesome dyskinesias. The total time in each state over 3 days is recorded (in hours). The total "bad time" is defined as "OFF time" and "ON time with troublesome dyskinesia". The total "good time" is defined as "ON time without dyskinesia" or "ON time with non-troublesome dyskinesia".
Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy]
Changes in health and daily activity assessed by a self-administered PDQ-39 questionnaire comprising of 39 questions related to eight key areas of health in Parkinson's patients: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication and bodily discomfort. Each question is evaluated on a scale of five terms "Never", "Occasionally", "Sometimes", "Often" or "Always or cannot do at all".
Change in CGI-I (Clinical Global Impression - Improvement) scale [efficacy]
Change in mental status as measured by CGI-I scale rated by the clinical on a seven-point scale 1-7 (1=very much improved, 4=no change, 7=very much worse).
Occurrence of blockage [performance assessment]
Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure at the infusion pump during infusion (in mmHg).
Stability of transcutaneous port: Inability to start infusion due to connectivity problem in Drug Delivery System
The stability of transcutaneous port is evaluated by recording the cases when the infusion in an individual patient has not been able to start due to connectivity problem between the external infusion set and the transcutaneous port.
Full Information
NCT ID
NCT03775538
First Posted
October 11, 2018
Last Updated
August 11, 2020
Sponsor
Herantis Pharma Plc.
Collaborators
Renishaw plc.
1. Study Identification
Unique Protocol Identification Number
NCT03775538
Brief Title
Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease. Extension to HP-CD-CL-2002 Clinical Study
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
July 5, 2018 (Actual)
Primary Completion Date
July 8, 2020 (Actual)
Study Completion Date
July 8, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Herantis Pharma Plc.
Collaborators
Renishaw plc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
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/
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Movement Disorders, Neuro-Degenerative Disease, Nervous System Diseases, Brain Diseases
Keywords
Parkinson, CDNF, Drug Delivery System, Intracerebral
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomised, Double-Blind, Active Treatment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-Blind
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CDNF mid-dose (400 micrograms)
Arm Type
Experimental
Arm Description
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.
Arm Title
CDNF high-dose (1200 micrograms)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cerebral Dopamine Neurotrophic Factor
Other Intervention Name(s)
CDNF
Intervention Description
Repeated intracerebral infusions
Intervention Type
Device
Intervention Name(s)
Renishaw Drug Delivery System
Other Intervention Name(s)
DDS
Intervention Description
Stereotactically implanted device
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
Description
Total number, causality and severity of adverse events at any time during the study period
Time Frame
Week 40 to Week 65
Title
Change in Electrocardiogram (ECG): Ventricular rate, PR interval, qRS duration, QT, QTc [safety-tolerability]
Description
Changes in electrical activity of heartbeat measured by electrocardiogram: Ventricular rate (bpm), PR interval (msec), QRS duration (msec), QT (msec), QTc (msec)
Time Frame
Week 40, Week 53 and Week 65
Title
Change in Beck Depression Inventory (BDI) score [safety-tolerability]
Description
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.
Time Frame
Week 40, Week 53 and Week 65
Title
Change in Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [safety-tolerability]
Description
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
Time Frame
Week 40, Week 53 and Week 65
Title
Change in Montreal cognitive assessment (MoCA) [safety-tolerability]
Description
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.
Time Frame
Week 40, Week 53 and Week 65
Title
Changes in physical examination: anatomic findings [safety-tolerability]
Description
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
Time Frame
Week 40 and Week 65
Title
Changes in physical examination: clinical standard neurological examination
Description
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
Time Frame
Week 40 and Week 65
Title
Changes in vital signs: blood pressure [safety-tolerability]
Description
Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)
Time Frame
Weeks 41, 45, 49, 53, 57, 61, and 63
Title
Changes in vital signs: pulse rate [safety-tolerability]
Description
Changes in pulse rate during the study (in beats per minute)
Time Frame
Weeks 41, 45, 49, 53, 57, 61, and 63
Title
Changes in vital signs: body temperature [safety-tolerability]
Description
Changes in body temperature during the study (in degrees celsius)
Time Frame
Weeks 41, 45, 49, 53, 57, 61, and 63
Title
Changes in vital signs: body weight [safety-tolerability]
Description
Changes in body weight during the study (in kilograms)
Time Frame
Weeks 41, 45, 49, 53, 57, 61, and 63
Title
Changes in vital signs: body mass index (BMI) [safety-tolerability]
Description
Changes in body mass index during the study (in kg/m^2)
Time Frame
Weeks 41, 45, 49, 53, 57, 61, and 63
Title
Changes in clinical laboratory safety screen: clinical chemistry [safety-tolerability]
Description
Changes in laboratory variables for clinical chemistry (Na, K, Urea, creatinine, creatine kinase, Ca, Bilirubin, IgG, Albumin, ALP, ALT, AST)
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: haematology - hemoglobin [safety-tolerability]
Description
Changes in laboratory variables for haematology: hemoglobin (g/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: haematology - hematocrit [safety-tolerability]
Description
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".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: haematology - red blood cell (RBC) count [safety-tolerability]
Description
Changes in laboratory variables for haematology: RBC count (10E12/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: mean cell volume (MCV) of red blood cells [safety-tolerability]
Description
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".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: mean cell hemoglobin of RBC (MHC) [safety-tolerability]
Description
Changes in laboratory variables for haematology: MCH (pg). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: Platelet count [safety-tolerability]
Description
Changes in laboratory variables for haematology: Platelet count (10E9/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: white blood cell (WBC) counts [safety-tolerability]
Description
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".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [safety-tolerability]
Description
Changes in laboratory variables for haematology: aPTT (sec) . Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [safety-tolerability]
Description
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".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Changes in clinical laboratory safety screen: urinanalysis [safety-tolerability]
Description
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".
Time Frame
Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Title
Formation of anti-CDNF antibodies [safety-tolerability]
Description
Formation and change in anti-CDNF antibody concentration (in ng/ml).
Time Frame
Weeks 40, 45, 49, 53, 57, 61, and 65
Title
Device related occurrence of adverse device effects [safety-tolerability]
Description
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.
Time Frame
Week 40 to Week 65
Secondary Outcome Measure Information:
Title
Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy]
Description
Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores (each scored 0-4; 0=none, 4=severe): Speech; facial expression; tremor a rest; Tremor of hands; rigidity; firger taps; hand movelents; alternating movement of hands; leg agility; rising from chair; posture; gait; postural stability; body bradykinesia and hypokinesia. The total score, the sum of scores received from 27 assessments, is 0 - 108
Time Frame
Week 40, Week 53 and Week 65
Title
Change in TUG (Timed Up and Go) test [efficacy]
Description
Changes in mobility assessed by TUG test (in minutes and seconds).
Time Frame
Week 40, Week 53 and Week 65
Title
Change in UPDRS Total score (Part I-IV) [efficacy]
Description
Change in severity of PD non-motor and motor symptoms assessed by UPDRS Part I-IV total scores (Parts I, II and IV in ON-state; Part III in OFF-state): Part 1 (scored 0-16) Mentation, behaviour and mood. Part 2 (scored 0-52) Activities of daily living. Part 3 (scored 0-108) Motor examination. Part 4 (scored 0-23) Complications of therapy. The total score is 0-199 (0=totally healthy; 199=worst possible).
Time Frame
Week 40, Week 53 and Week 65
Title
Change in home diary score [efficacy]
Description
Change in functional status of the patient's dyskinesias assessed by home diary score for three-day period. Each half hour is scored: sleep, OFF, ON without dyskinesias, ON with non-troublesome dyskinesias, ON with troublesome dyskinesias. The total time in each state over 3 days is recorded (in hours). The total "bad time" is defined as "OFF time" and "ON time with troublesome dyskinesia". The total "good time" is defined as "ON time without dyskinesia" or "ON time with non-troublesome dyskinesia".
Time Frame
Weeks 40, 45, 49, 49, 53, 57, 61 and 65
Title
Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy]
Description
Changes in health and daily activity assessed by a self-administered PDQ-39 questionnaire comprising of 39 questions related to eight key areas of health in Parkinson's patients: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication and bodily discomfort. Each question is evaluated on a scale of five terms "Never", "Occasionally", "Sometimes", "Often" or "Always or cannot do at all".
Time Frame
Week 40, Week 53 and Week 65
Title
Change in CGI-I (Clinical Global Impression - Improvement) scale [efficacy]
Description
Change in mental status as measured by CGI-I scale rated by the clinical on a seven-point scale 1-7 (1=very much improved, 4=no change, 7=very much worse).
Time Frame
Weeks 40, 45, 49, 53, 57, 61 and 65
Title
Occurrence of blockage [performance assessment]
Description
Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure at the infusion pump during infusion (in mmHg).
Time Frame
Week 41, 45, 49, 53, 57 and Week 61
Title
Stability of transcutaneous port: Inability to start infusion due to connectivity problem in Drug Delivery System
Description
The stability of transcutaneous port is evaluated by recording the cases when the infusion in an individual patient has not been able to start due to connectivity problem between the external infusion set and the transcutaneous port.
Time Frame
Week 41 to Week 61
Other Pre-specified Outcome Measures:
Title
Change in DAT (dopamine transporter)-PET imaging [exploratory]
Description
Change in caudate and putamen DAT availability using PET imaging.
Time Frame
Week 63
Title
Change in alpha-synuclein levels [exploratory]
Description
Changes in serum and CSF (cerebrospinal fluid) concentrations of various α-synuclein species
Time Frame
Week 40, Week Week 61 and Week 65
Title
Distribution of CDNF: blood serum [exploratory]
Description
Concentration of CDNF in serum before and two timepoints after infusion (in ng/ml)
Time Frame
Week 61
Title
Distribution of CDNF: cerebrospinal fluid [exploratory]
Description
Maximum concentration (Cmax) of CDNF in cerebrospinal fluid (CSF) after infusion (in ng/ml)
Time Frame
Week 61
Title
Change in daily activity measurement [exploratory]
Description
Change in daily activity measured by Parkinson's KinetiGraph™ (PKG™) Data Logger: dyskinesia, bradykinesia, tremor, immobility plot, fluctuation score. The PKG units are: Bradykinesia score in % from normal controls, and, Dyskinesia score in % from normal controls. The Fluctuation and Dyskinesia score (FDS) for normal controls is in the range of 7.8-12.8: a lower score indicates bradykinesia and a higher score indicates dyskinesia.
Time Frame
Weeks 40, 45, 49, 53, 57, 61 and 65
Title
Coverage of infusate in target anatomy assessed by Magnetic resonance imaging
Description
Coverage of the infusate in target anatomy assessed by MRI (Magnetic resonance imaging)
Time Frame
Week 61
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Per Svenningsson, MD, Prof.
Organizational Affiliation
Karolinska University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Helsinki University Hospital
City
Helsinki
ZIP/Postal Code
00029
Country
Finland
Facility Name
Skåne University Hospital
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Karolinska University Hospital
City
Stockholm
ZIP/Postal Code
14186
Country
Sweden
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease. Extension to HP-CD-CL-2002 Clinical Study
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