Clinical trial NCT03775538: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Movement Disorders
Neuro-Degenerative Disease
Nervous System Diseases
Brain Diseases
Keywords: Parkinson
CDNF
Drug Delivery System
Intracerebral
Lead sponsor: Herantis Pharma Plc.
Sponsor class: INDUSTRY
Collaborators: name: Renishaw plc.
First posted: 2018-12-14
Enrollment: 15
Sex: ALL
Minimum age (years): 35
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, Double-Blind, Active Treatment
Primary purpose: TREATMENT

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/

Eligibility criteria: Inclusion Criteria:

1. Completion of 6 months treatment period in the Main study (HP-CD-CL-2002) including End-of-Study assessment
2. 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.
3. At least one functioning catheter in each putamen
4. Provision of informed consent

Exclusion Criteria:

1. Drug-resistant rest tremor, severe dyskinesia or severe head tremor, which could interfere with treatment infusions
2. Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsy, CSF shunt or other implanted central nervous system device
3. Changes in pathology which give rise to safety concern such as sequelae from catheter implantation, clinically significant intracerebral trauma, oedema, haemorrhage, or infection
4. Current psychosis requiring therapy
5. Presence of clinically significant impulse control disorder by a positive screen on the QUIP-RS questionnaire score \>20, or, presence of dopamine dysregulation syndrome
6. 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
7. Medical conditions, which might impair outcome measure assessments or safety measures
8. Impaired renal function
9. Concomitant treatment with neuroleptics or antipsychotic medication prescribed for treatment of current psychosis, central dopamine blockers or tricyclic antidepressants

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
timeFrame: Week 40 to Week 65
measure: Change in Electrocardiogram (ECG): Ventricular rate, PR interval, qRS duration, QT, QTc [safety-tolerability]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in Beck Depression Inventory (BDI) score [safety-tolerability]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [safety-tolerability]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in Montreal cognitive assessment (MoCA) [safety-tolerability]
timeFrame: Week 40, Week 53 and Week 65
measure: Changes in physical examination: anatomic findings [safety-tolerability]
timeFrame: Week 40 and Week 65
measure: Changes in physical examination: clinical standard neurological examination
timeFrame: Week 40 and Week 65
measure: Changes in vital signs: blood pressure [safety-tolerability]
timeFrame: Weeks 41, 45, 49, 53, 57, 61, and 63
measure: Changes in vital signs: pulse rate [safety-tolerability]
timeFrame: Weeks 41, 45, 49, 53, 57, 61, and 63
measure: Changes in vital signs: body temperature [safety-tolerability]
timeFrame: Weeks 41, 45, 49, 53, 57, 61, and 63
measure: Changes in vital signs: body weight [safety-tolerability]
timeFrame: Weeks 41, 45, 49, 53, 57, 61, and 63
measure: Changes in vital signs: body mass index (BMI) [safety-tolerability]
timeFrame: Weeks 41, 45, 49, 53, 57, 61, and 63
measure: Changes in clinical laboratory safety screen: clinical chemistry [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: haematology - hemoglobin [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: haematology - hematocrit [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: haematology - red blood cell (RBC) count [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: mean cell volume (MCV) of red blood cells [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: mean cell hemoglobin of RBC (MHC) [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: Platelet count [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: white blood cell (WBC) counts [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Changes in clinical laboratory safety screen: urinanalysis [safety-tolerability]
timeFrame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
measure: Formation of anti-CDNF antibodies [safety-tolerability]
timeFrame: Weeks 40, 45, 49, 53, 57, 61, and 65
measure: Device related occurrence of adverse device effects [safety-tolerability]
timeFrame: Week 40 to Week 65
Secondary outcomes:
measure: Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in TUG (Timed Up and Go) test [efficacy]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in UPDRS Total score (Part I-IV) [efficacy]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in home diary score [efficacy]
timeFrame: Weeks 40, 45, 49, 49, 53, 57, 61 and 65
measure: Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy]
timeFrame: Week 40, Week 53 and Week 65
measure: Change in CGI-I (Clinical Global Impression - Improvement) scale [efficacy]
timeFrame: Weeks 40, 45, 49, 53, 57, 61 and 65
measure: Occurrence of blockage [performance assessment]
timeFrame: Week 41, 45, 49, 53, 57 and Week 61
measure: Stability of transcutaneous port: Inability to start infusion due to connectivity problem in Drug Delivery System
timeFrame: Week 41 to Week 61
Other outcomes:
measure: Change in DAT (dopamine transporter)-PET imaging [exploratory]
timeFrame: Week 63
measure: Change in alpha-synuclein levels [exploratory]
timeFrame: Week 40, Week Week 61 and Week 65
measure: Distribution of CDNF: blood serum [exploratory]
timeFrame: Week 61
measure: Distribution of CDNF: cerebrospinal fluid [exploratory]
timeFrame: Week 61
measure: Change in daily activity measurement [exploratory]
timeFrame: Weeks 40, 45, 49, 53, 57, 61 and 65
measure: Coverage of infusate in target anatomy assessed by Magnetic resonance imaging
timeFrame: Week 61
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Lund
country: Sweden
facility: Skåne University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
affiliation: Karolinska University Hospital
name: Per Svenningsson, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References: