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

NCT03295786 | Completed Phase 1 DMC

• 2 other identifiers: HP-CD-CL-20022015-004175-73
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 3

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.

Conditions

Parkinson Disease; Movement Disorders; Neurodegenerative Diseases; Nervous System Diseases; Brain Diseases

Keywords

Parkinson; CDNF; Drug Delivery System; Intracerebral

Outcome Measures

Primary Outcomes (11)

• Adverse events (AEs)

  Number and severity of adverse events

  Week 15 to Week 40

• Electrocardiogram (ECG)

  Changes in electrical activity of heartbeat measured by electrocardiogram

  Week 15 to Week 40

• Beck Depression Inventory (BDI) score

  Assessment of change in depression using Beck Depression Inventory (BDI) score

  Week 15 to Week 40

• Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS)

  Assessment of changes in impulsive-compulsive disorders using QUIP\_RS

  Week 15 to Week 40

• Montreal cognitive assessment (MoCA)

  Assessment of change in cognitive domains using MoCA test

  Week 15 to Week 40

• Physical examination

  Changes in anatomic findings found in physical examination

  Week 15 to Week 40

• Vital signs

  Changes in vital signs

  Week 15 to Week 40

• Clinical laboratory safety screen

  Changes in clinical laboratory variables (chemistry, haematology, urinanalysis)

  Week 15 to Week 40

• Formation of anti-CDNF antibodies

  Change in anti-CDNF antibody concentration

  Week 15 to Week 40

• Device related changes in safety measures

  Occurrence of adverse device effects (ADE), 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.

  Week 8 to Week 40

• Device related accuracy of implantation

  The accuracy of implantation of the Drug Delivery System (DDS) will be measured comparing the tip of each individual catheters defined in the plan of the surgical procedure with the position of those measured by the post-operative CT scan.

  Week 8

Secondary Outcomes (8)

• UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score

  Week 15 to Week 40

• TUG (Timed Up and Go) test

  Week 15 to Week 40

• UPDRS Total score (Part I-IV)

  Week 15 to Week 40

• Home diary score

  Week 16 to Week 24

• PDQ-39 (Parkinson's Disease Questionnaire) score

  Week 15 to Week 40

Other Outcomes (5)

• DAT (dopamine transporter)-PET imaging

  Week 14 to Week 38

• alpha-synuclein levels

  Week 15 to Week 40

• Distribution of CDNF

  Week 24 and Week 36

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Patients randomized to this group will receive 6 monthly infusions of placebo/vehicle

Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System

CDNF mid-dose

EXPERIMENTAL

Patients randomized to this group will receive 6 doses of CDNF titrated to mid-dose

Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System

CDNF high-dose

EXPERIMENTAL

Patients randomized to this group will receive 6 doses of CDNF titrated to high-dose

Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System

Interventions

Cerebral Dopamine Neurotrophic Factor DRUG

Repeated intracerebral infusions

Also known as: CDNF

CDNF high-dose; CDNF mid-dose; Placebo

Renishaw Drug Delivery System DEVICE

Stereotactically implanted device

Also known as: DDS

CDNF high-dose; CDNF mid-dose; Placebo

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Diagnosed with atypical parkinsonism or any known secondary parkinsonian syndrome.
• Signs or symptoms suggestive of atypical parkinsonian syndrome.
• Drug-resistant rest tremor.
• Prior neurosurgical treatment for PD, including lesioning or deep brain stimulation
• Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsia, CSF shunt or other implanted CNS device
• Presence of significant depression as defined as a BDI score ≥ 20
• Current psychosis requiring therapy.
• Presence of clinically significant impulse control disorder ((QUIP-RS) score \> 20), or, presence of dopamine dysregulation syndrome.
• MoCA score \< 24.
• Use within 3 months of planned catheter insertion of concomitant medications known to affect PD symptoms other than prescribed PD therapy.
• Any medical condition, which might impair outcome measure assessments or safety measures including ability to undergo MRI or DAT-PET.
• Hypersensitivity or allergy to gadolinium or to any of excipients of macrocyclic GBCA used for the surgical planning MRI.
• Screening and/or planning MRI demonstrating any abnormality, which would suggest an alternative cause for patient's parkinsonism or preclude neurosurgery.
• 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
• History within the last 5 years of cancer with the exception of basal cell carcinoma of the skin

Sponsors & Collaborators

• Herantis Pharma Plc.: lead
• Renishaw plc.: collaborator

Study Sites (3)

Helsinki University Hospital

Helsinki, 00029, Finland

Location

Skåne University Hospital

Lund, 221 85, Sweden

Location

Karolinska University Hospital, Huddinge

Stockholm, 141 86, Sweden

Location

MeSH Terms

Conditions

Parkinson Disease; Movement Disorders; Neurodegenerative Diseases; Nervous System Diseases; Brain Diseases

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Central Nervous System Diseases; Synucleinopathies

Study Officials

• Per Svenningsson, MD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomised, Double-Blind, Placebo Controlled

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 28, 2017
• Study Start: September 26, 2017
• Primary Completion: December 19, 2019
• Study Completion: December 19, 2019
• Last Updated: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1); SE (2)