Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease

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

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.

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/

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