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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03295786
Recruitment Status : Completed
First Posted : September 28, 2017
Last Update Posted : January 13, 2020
Sponsor:
Collaborator:
Renishaw plc.
Information provided by (Responsible Party):
Herantis Pharma Plc.

Tracking Information
First Submitted Date  ICMJE September 14, 2017
First Posted Date  ICMJE September 28, 2017
Last Update Posted Date January 13, 2020
Actual Study Start Date  ICMJE September 26, 2017
Actual Primary Completion Date December 19, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 25, 2017)
  • Adverse events (AEs) [ Time Frame: Week 15 to Week 40 ]
    Number and severity of adverse events
  • Electrocardiogram (ECG) [ Time Frame: Week 15 to Week 40 ]
    Changes in electrical activity of heartbeat measured by electrocardiogram
  • Beck Depression Inventory (BDI) score [ Time Frame: Week 15 to Week 40 ]
    Assessment of change in depression using Beck Depression Inventory (BDI) score
  • Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [ Time Frame: Week 15 to Week 40 ]
    Assessment of changes in impulsive-compulsive disorders using QUIP_RS
  • Montreal cognitive assessment (MoCA) [ Time Frame: Week 15 to Week 40 ]
    Assessment of change in cognitive domains using MoCA test
  • Physical examination [ Time Frame: Week 15 to Week 40 ]
    Changes in anatomic findings found in physical examination
  • Vital signs [ Time Frame: Week 15 to Week 40 ]
    Changes in vital signs
  • Clinical laboratory safety screen [ Time Frame: Week 15 to Week 40 ]
    Changes in clinical laboratory variables (chemistry, haematology, urinanalysis)
  • Formation of anti-CDNF antibodies [ Time Frame: Week 15 to Week 40 ]
    Change in anti-CDNF antibody concentration
  • Device related changes in safety measures [ Time Frame: Week 8 to Week 40 ]
    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.
  • Device related accuracy of implantation [ Time Frame: Week 8 ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 10, 2018)
  • UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [ Time Frame: Week 15 to Week 40 ]
    Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores
  • TUG (Timed Up and Go) test [ Time Frame: Week 15 to Week 40 ]
    Changes in mobility assessed by TUG test
  • UPDRS Total score (Part I-IV) [ Time Frame: Week 15 to Week 40 ]
    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).
  • Home diary score [ Time Frame: Week 16 to Week 24 ]
    Change in functional status assessed by home diary score
  • PDQ-39 (Parkinson's Disease Questionnaire) score [ Time Frame: Week 15 to Week 40 ]
    Changes in health and daily activity assessed by PDQ-39 questionnaire score
  • change in CGI (Clinical Global Impressions) scale [ Time Frame: Week 16 to Week 40 ]
    • Change from baseline until end of treatment evaluation in mental status as measured by CGI scale.
  • Occurrence of blockage [ Time Frame: Week 11 to Week 36 ]
    Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure
  • Cessation of infusions [ Time Frame: Week 11 to Week 36 ]
    Cessation of infusions in an individual patient
Original Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2017)
  • UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [ Time Frame: Week 15 to Week 40 ]
    Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores
  • TUG (Timed Up and Go) test [ Time Frame: Week 15 to Week 40 ]
    Changes in mobility assessed by TUG test
  • UPDRS Total score (Part I-IV) [ Time Frame: Week 15 to Week 40 ]
    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).
  • Home diary score [ Time Frame: Week 16 to Week 24 ]
    Change in functional status assessed by home diary score
  • PDQ-39 (Parkinson's Disease Questionnaire) score [ Time Frame: Week 15 to Week 40 ]
    Changes in health and daily activity assessed by PDQ-39 questionnaire score
  • change in CGI (Clinical Global Impressions) scale [ Time Frame: Week 16 to Week 40 ]
    • Change from baseline until end of treatment evaluation in mental status as measured by CGI scale.
  • Coverage of infusate [ Time Frame: Week 11 to Week 38 ]
    Coverage of the infusate in target anatomy assessed by MRI (Magnetic resonance imaging)
  • Occurrence of blockage [ Time Frame: Week 11 to Week 38 ]
    Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure
  • Cessation of infusions [ Time Frame: Week 11 to Week 38 ]
    Cessation of infusions in an individual patient
Current Other Pre-specified Outcome Measures
 (submitted: April 10, 2018)
  • DAT (dopamine transporter)-PET imaging [ Time Frame: Week 14 to Week 38 ]
    Change in caudate and putamen DAT availability using PET imaging.
  • alpha-synuclein levels [ Time Frame: Week 15 to Week 40 ]
    Changes in serum and CSF (cerebrospinal fluid) concentrations of various α-synuclein species
  • Distribution of CDNF [ Time Frame: Week 24 and Week 36 ]
    Level of distribution of CDNF in serum and Cmax of CDNF in CSF
  • Daily activity measurement [ Time Frame: Week 16 to Week 40 ]
    Change in daily activity measured by Parkinson's KinetiGraph™ (PKG™) Data Logger
  • Coverage of infusate [ Time Frame: Week 11 to Week 36 ]
    Coverage of the infusate in target anatomy assessed by MRI (Magnetic resonance imaging)
Original Other Pre-specified Outcome Measures
 (submitted: September 25, 2017)
  • DAT (dopamine transporter)-PET imaging [ Time Frame: Week 15 to Week 39 ]
    Change in caudate and putamen DAT availability using PET imaging.
  • alpha-synuclein levels [ Time Frame: Week 15 to Week 36 ]
    Changes in serum and CSF (cerebrospinal fluid) concentrations of various α-synuclein species
  • Distribution of CDNF [ Time Frame: Week 24 and Week 36 ]
    Level of distribution of CDNF in serum and Cmax of CDNF in CSF
  • Daily activity measurement [ Time Frame: Week 16 to Week 40 ]
    Change in daily activity measured by Parkinson's KinetiGraph™ (PKG™) Data Logger
 
Descriptive Information
Brief Title  ICMJE Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease
Official Title  ICMJE 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
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/

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomised, Double-Blind, Placebo Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-Blind
Primary Purpose: Treatment
Condition  ICMJE
  • Parkinson Disease
  • Movement Disorders
  • Neurodegenerative Diseases
  • Nervous System Diseases
  • Brain Diseases
Intervention  ICMJE
  • Drug: Cerebral Dopamine Neurotrophic Factor
    Repeated intracerebral infusions
    Other Name: CDNF
  • Device: Renishaw Drug Delivery System
    Stereotactically implanted device
    Other Name: DDS
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Patients randomized to this group will receive 6 monthly infusions of placebo/vehicle
    Interventions:
    • Drug: Cerebral Dopamine Neurotrophic Factor
    • Device: Renishaw Drug Delivery System
  • Experimental: CDNF mid-dose
    Patients randomized to this group will receive 6 doses of CDNF titrated to mid-dose
    Interventions:
    • Drug: Cerebral Dopamine Neurotrophic Factor
    • Device: Renishaw Drug Delivery System
  • Experimental: CDNF high-dose
    Patients randomized to this group will receive 6 doses of CDNF titrated to high-dose
    Interventions:
    • Drug: Cerebral Dopamine Neurotrophic Factor
    • Device: Renishaw Drug Delivery System
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 25, 2019)
17
Original Estimated Enrollment  ICMJE
 (submitted: September 25, 2017)
18
Actual Study Completion Date  ICMJE December 19, 2019
Actual Primary Completion Date December 19, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 35 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Finland,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03295786
Other Study ID Numbers  ICMJE HP-CD-CL-2002
2015-004175-73 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Herantis Pharma Plc.
Study Sponsor  ICMJE Herantis Pharma Plc.
Collaborators  ICMJE Renishaw plc.
Investigators  ICMJE
Principal Investigator: Per Svenningsson, MD Karolinska University Hospital
PRS Account Herantis Pharma Plc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP