Clinical trial NCT03295786: Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease
Official title: Phase 1-2, Randomised, Double-Blind, Placebo Controlled, Safety and Tolerability Study of Intraputamenal Cerebral Dopamine Neurotrophic Factor (CDNF) Infusions Via an Investigational Drug Delivery System to Patients With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Parkinson Disease
Movement Disorders
Neurodegenerative Diseases
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: 2017-09-28
Enrollment: 17
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, Placebo Controlled
Primary purpose: TREATMENT

Brief summary: This study evaluates the 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). Safety and accuracy of the DDS is also being evaluated. One-third of the patients will receive monthly infusions with placebo and two-third of the patients will receive monthly infusions with either mid- or high-doses of CDNF for a period of 6 months.

Detailed description: A patient's participation in the study will last for ten months and will include sixteen to seventeen visits:

* Screening (2 visits)
* Planning of surgery - Surgery: implantation of drug delivery system - Post-surgery follow-up (3 visits)
* Test infusions with vehicle (1-2 visits)
* Positron emission tomography (PET) examinations before the first and after the last dose (2 visits)
* Baseline and randomisation to CDNF or placebo group (1 visit)
* Dosing visits: CDNF or placebo (6 visits)
* End-of-study visit (1 visit)

Study examinations and assessments

- Physical examination: pulse rate, blood pressure, temperature, body weight and height

* ECG (electrocardiography) and blood and urine tests
* HIV, hepatitis B and C blood tests (on first visit)
* 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 device worn on the wrist for certain periods during the study to record movements
* 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)
* Computed tomography (CT)

For more information: https://treater.eu/clinical-study/

Eligibility criteria: Inclusion Criteria:

1. Idiopathic Parkinson's disease based on UK brain bank criteria
2. Duration of PD motor symptoms 5-15 years (inclusive)
3. Age 35-75 years (inclusive)
4. Presence of motor fluctuations.
5. At least 5 daily doses of levodopa
6. Ability to reliably distinguish motor states and accurately complete fluctuation diaries
7. UPDRS motor score (part III) in a practically defined OFF-state between 25-50 (inclusive)
8. Hoehn and Yahr ≤ stage III in the OFF-state
9. Responsiveness to levodopa
10. No change in anti-parkinsonian medication for 6 weeks before screening
11. Provision of Informed Consent

Exclusion Criteria:

1. Diagnosed with atypical parkinsonism or any known secondary parkinsonian syndrome.
2. Signs or symptoms suggestive of atypical parkinsonian syndrome.
3. Drug-resistant rest tremor.
4. Prior neurosurgical treatment for PD, including lesioning or deep brain stimulation
5. Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsia, CSF shunt or other implanted CNS device
6. Presence of significant depression as defined as a BDI score ≥ 20
7. Current psychosis requiring therapy.
8. Presence of clinically significant impulse control disorder ((QUIP-RS) score \> 20), or, presence of dopamine dysregulation syndrome.
9. MoCA score \< 24.
10. Use within 3 months of planned catheter insertion of concomitant medications known to affect PD symptoms other than prescribed PD therapy.
11. Any medical condition, which might impair outcome measure assessments or safety measures including ability to undergo MRI or DAT-PET.
12. Hypersensitivity or allergy to gadolinium or to any of excipients of macrocyclic GBCA used for the surgical planning MRI.
13. Screening and/or planning MRI demonstrating any abnormality, which would suggest an alternative cause for patient's parkinsonism or preclude neurosurgery.
14. Any medical condition that would put the patient at undue risk from surgical treatment or chronic implants including but not limited to bleeding disorders, chronic infections, or immunosuppressive illness
15. History within the last 5 years of cancer with the exception of basal cell carcinoma of the skin
16. History of drug or alcohol abuse within 2 years of screening
17. Use of any investigational drug or device within 90 days of screening
18. Active breastfeeding

Primary outcomes:
measure: Adverse events (AEs)
timeFrame: Week 15 to Week 40
measure: Electrocardiogram (ECG)
timeFrame: Week 15 to Week 40
measure: Beck Depression Inventory (BDI) score
timeFrame: Week 15 to Week 40
measure: Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS)
timeFrame: Week 15 to Week 40
measure: Montreal cognitive assessment (MoCA)
timeFrame: Week 15 to Week 40
measure: Physical examination
timeFrame: Week 15 to Week 40
measure: Vital signs
timeFrame: Week 15 to Week 40
measure: Clinical laboratory safety screen
timeFrame: Week 15 to Week 40
measure: Formation of anti-CDNF antibodies
timeFrame: Week 15 to Week 40
measure: Device related changes in safety measures
timeFrame: Week 8 to Week 40
measure: Device related accuracy of implantation
timeFrame: Week 8
Secondary outcomes:
measure: UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score
timeFrame: Week 15 to Week 40
measure: TUG (Timed Up and Go) test
timeFrame: Week 15 to Week 40
measure: UPDRS Total score (Part I-IV)
timeFrame: Week 15 to Week 40
measure: Home diary score
timeFrame: Week 16 to Week 24
measure: PDQ-39 (Parkinson's Disease Questionnaire) score
timeFrame: Week 15 to Week 40
measure: change in CGI (Clinical Global Impressions) scale
timeFrame: Week 16 to Week 40
measure: Occurrence of blockage
timeFrame: Week 11 to Week 36
measure: Cessation of infusions
timeFrame: Week 11 to Week 36
Other outcomes:
measure: DAT (dopamine transporter)-PET imaging
timeFrame: Week 14 to Week 38
measure: alpha-synuclein levels
timeFrame: Week 15 to Week 40
measure: Distribution of CDNF
timeFrame: Week 24 and Week 36
measure: Daily activity measurement
timeFrame: Week 16 to Week 40
measure: Coverage of infusate
timeFrame: Week 11 to Week 36
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, Huddinge
Study officials:
affiliation: Karolinska University Hospital
name: Per Svenningsson, MD
role: PRINCIPAL_INVESTIGATOR
References: