<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03295786</url>
  </required_header>
  <id_info>
    <org_study_id>HP-CD-CL-2002</org_study_id>
    <secondary_id>2015-004175-73</secondary_id>
    <nct_id>NCT03295786</nct_id>
  </id_info>
  <brief_title>Clinical Study to Test the Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Herantis Pharma Plc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Renishaw plc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Herantis Pharma Plc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the safety and tolerability of CDNF in patients with Parkinson's&#xD;
      disease, when dosed directly into the brain using an implanted investigational drug delivery&#xD;
      system (DDS). Safety and accuracy of the DDS is also being evaluated. One-third of the&#xD;
      patients will receive monthly infusions with placebo and two-third of the patients will&#xD;
      receive monthly infusions with either mid- or high-doses of CDNF for a period of 6 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A patient's participation in the study will last for ten months and will include sixteen to&#xD;
      seventeen visits:&#xD;
&#xD;
        -  Screening (2 visits)&#xD;
&#xD;
        -  Planning of surgery - Surgery: implantation of drug delivery system - Post-surgery&#xD;
           follow-up (3 visits)&#xD;
&#xD;
        -  Test infusions with vehicle (1-2 visits)&#xD;
&#xD;
        -  Positron emission tomography (PET) examinations before the first and after the last dose&#xD;
           (2 visits)&#xD;
&#xD;
        -  Baseline and randomisation to CDNF or placebo group (1 visit)&#xD;
&#xD;
        -  Dosing visits: CDNF or placebo (6 visits)&#xD;
&#xD;
        -  End-of-study visit (1 visit)&#xD;
&#xD;
      Study examinations and assessments&#xD;
&#xD;
      - Physical examination: pulse rate, blood pressure, temperature, body weight and height&#xD;
&#xD;
        -  ECG (electrocardiography) and blood and urine tests&#xD;
&#xD;
        -  HIV, hepatitis B and C blood tests (on first visit)&#xD;
&#xD;
        -  Pregnancy tests for women of childbearing age&#xD;
&#xD;
        -  Completion of a patient diary to record mobility and time asleep&#xD;
&#xD;
        -  Parkinson's Kinetigraph (PKGTM) Data Logger: a watch-type device worn on the wrist for&#xD;
           certain periods during the study to record movements&#xD;
&#xD;
        -  Questionnaires, rating scales and forms: quality of life, mood, memory, impulse control,&#xD;
           mental health&#xD;
&#xD;
        -  Assessment of the port and the skin around the port&#xD;
&#xD;
        -  Cerebrospinal fluid sampling by lumbar puncture&#xD;
&#xD;
        -  Magnetic resonance imaging (MRI)&#xD;
&#xD;
        -  Positron emission tomography scans (PET)&#xD;
&#xD;
        -  Computed tomography (CT)&#xD;
&#xD;
      For more information: https://treater.eu/clinical-study/&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2017</start_date>
  <completion_date type="Actual">December 19, 2019</completion_date>
  <primary_completion_date type="Actual">December 19, 2019</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomised, Double-Blind, Placebo Controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events (AEs)</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Number and severity of adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Electrocardiogram (ECG)</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in electrical activity of heartbeat measured by electrocardiogram</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Beck Depression Inventory (BDI) score</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Assessment of change in depression using Beck Depression Inventory (BDI) score</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS)</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Assessment of changes in impulsive-compulsive disorders using QUIP_RS</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Montreal cognitive assessment (MoCA)</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Assessment of change in cognitive domains using MoCA test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Physical examination</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in anatomic findings found in physical examination</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vital signs</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in vital signs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical laboratory safety screen</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in clinical laboratory variables (chemistry, haematology, urinanalysis)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Formation of anti-CDNF antibodies</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Change in anti-CDNF antibody concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Device related changes in safety measures</measure>
    <time_frame>Week 8 to Week 40</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Device related accuracy of implantation</measure>
    <time_frame>Week 8</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TUG (Timed Up and Go) test</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in mobility assessed by TUG test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>UPDRS Total score (Part I-IV)</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Home diary score</measure>
    <time_frame>Week 16 to Week 24</time_frame>
    <description>Change in functional status assessed by home diary score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PDQ-39 (Parkinson's Disease Questionnaire) score</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in health and daily activity assessed by PDQ-39 questionnaire score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>change in CGI (Clinical Global Impressions) scale</measure>
    <time_frame>Week 16 to Week 40</time_frame>
    <description>• Change from baseline until end of treatment evaluation in mental status as measured by CGI scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of blockage</measure>
    <time_frame>Week 11 to Week 36</time_frame>
    <description>Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cessation of infusions</measure>
    <time_frame>Week 11 to Week 36</time_frame>
    <description>Cessation of infusions in an individual patient</description>
  </secondary_outcome>
  <other_outcome>
    <measure>DAT (dopamine transporter)-PET imaging</measure>
    <time_frame>Week 14 to Week 38</time_frame>
    <description>Change in caudate and putamen DAT availability using PET imaging.</description>
  </other_outcome>
  <other_outcome>
    <measure>alpha-synuclein levels</measure>
    <time_frame>Week 15 to Week 40</time_frame>
    <description>Changes in serum and CSF (cerebrospinal fluid) concentrations of various α-synuclein species</description>
  </other_outcome>
  <other_outcome>
    <measure>Distribution of CDNF</measure>
    <time_frame>Week 24 and Week 36</time_frame>
    <description>Level of distribution of CDNF in serum and Cmax of CDNF in CSF</description>
  </other_outcome>
  <other_outcome>
    <measure>Daily activity measurement</measure>
    <time_frame>Week 16 to Week 40</time_frame>
    <description>Change in daily activity measured by Parkinson's KinetiGraph™ (PKG™) Data Logger</description>
  </other_outcome>
  <other_outcome>
    <measure>Coverage of infusate</measure>
    <time_frame>Week 11 to Week 36</time_frame>
    <description>Coverage of the infusate in target anatomy assessed by MRI (Magnetic resonance imaging)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Movement Disorders</condition>
  <condition>Neurodegenerative Diseases</condition>
  <condition>Nervous System Diseases</condition>
  <condition>Brain Diseases</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients randomized to this group will receive 6 monthly infusions of placebo/vehicle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CDNF mid-dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to this group will receive 6 doses of CDNF titrated to mid-dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CDNF high-dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients randomized to this group will receive 6 doses of CDNF titrated to high-dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cerebral Dopamine Neurotrophic Factor</intervention_name>
    <description>Repeated intracerebral infusions</description>
    <arm_group_label>CDNF high-dose</arm_group_label>
    <arm_group_label>CDNF mid-dose</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>CDNF</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Renishaw Drug Delivery System</intervention_name>
    <description>Stereotactically implanted device</description>
    <arm_group_label>CDNF high-dose</arm_group_label>
    <arm_group_label>CDNF mid-dose</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>DDS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Idiopathic Parkinson's disease based on UK brain bank criteria&#xD;
&#xD;
          2. Duration of PD motor symptoms 5-15 years (inclusive)&#xD;
&#xD;
          3. Age 35-75 years (inclusive)&#xD;
&#xD;
          4. Presence of motor fluctuations.&#xD;
&#xD;
          5. At least 5 daily doses of levodopa&#xD;
&#xD;
          6. Ability to reliably distinguish motor states and accurately complete fluctuation&#xD;
             diaries&#xD;
&#xD;
          7. UPDRS motor score (part III) in a practically defined OFF-state between 25-50&#xD;
             (inclusive)&#xD;
&#xD;
          8. Hoehn and Yahr ≤ stage III in the OFF-state&#xD;
&#xD;
          9. Responsiveness to levodopa&#xD;
&#xD;
         10. No change in anti-parkinsonian medication for 6 weeks before screening&#xD;
&#xD;
         11. Provision of Informed Consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosed with atypical parkinsonism or any known secondary parkinsonian syndrome.&#xD;
&#xD;
          2. Signs or symptoms suggestive of atypical parkinsonian syndrome.&#xD;
&#xD;
          3. Drug-resistant rest tremor.&#xD;
&#xD;
          4. Prior neurosurgical treatment for PD, including lesioning or deep brain stimulation&#xD;
&#xD;
          5. Significant neurological disorder other than PD including clinically significant head&#xD;
             trauma, cerebrovascular disease, epilepsia, CSF shunt or other implanted CNS device&#xD;
&#xD;
          6. Presence of significant depression as defined as a BDI score ≥ 20&#xD;
&#xD;
          7. Current psychosis requiring therapy.&#xD;
&#xD;
          8. Presence of clinically significant impulse control disorder ((QUIP-RS) score &gt; 20),&#xD;
             or, presence of dopamine dysregulation syndrome.&#xD;
&#xD;
          9. MoCA score &lt; 24.&#xD;
&#xD;
         10. Use within 3 months of planned catheter insertion of concomitant medications known to&#xD;
             affect PD symptoms other than prescribed PD therapy.&#xD;
&#xD;
         11. Any medical condition, which might impair outcome measure assessments or safety&#xD;
             measures including ability to undergo MRI or DAT-PET.&#xD;
&#xD;
         12. Hypersensitivity or allergy to gadolinium or to any of excipients of macrocyclic GBCA&#xD;
             used for the surgical planning MRI.&#xD;
&#xD;
         13. Screening and/or planning MRI demonstrating any abnormality, which would suggest an&#xD;
             alternative cause for patient's parkinsonism or preclude neurosurgery.&#xD;
&#xD;
         14. Any medical condition that would put the patient at undue risk from surgical treatment&#xD;
             or chronic implants including but not limited to bleeding disorders, chronic&#xD;
             infections, or immunosuppressive illness&#xD;
&#xD;
         15. History within the last 5 years of cancer with the exception of basal cell carcinoma&#xD;
             of the skin&#xD;
&#xD;
         16. History of drug or alcohol abuse within 2 years of screening&#xD;
&#xD;
         17. Use of any investigational drug or device within 90 days of screening&#xD;
&#xD;
         18. Active breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per Svenningsson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Karolinska University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helsinki University Hospital</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Skåne University Hospital</name>
      <address>
        <city>Lund</city>
        <zip>221 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital, Huddinge</name>
      <address>
        <city>Stockholm</city>
        <zip>141 86</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>January 10, 2020</last_update_submitted>
  <last_update_submitted_qc>January 10, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson</keyword>
  <keyword>CDNF</keyword>
  <keyword>Drug Delivery System</keyword>
  <keyword>Intracerebral</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Nervous System Diseases</mesh_term>
    <mesh_term>Movement Disorders</mesh_term>
    <mesh_term>Neurodegenerative Diseases</mesh_term>
    <mesh_term>Brain Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dopamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03295786
org study id: HP-CD-CL-2002
secondary id: 2015-004175-73
nct id: NCT03295786
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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/
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomised, Double-Blind, Placebo Controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-Blind
measure: Adverse events (AEs)
time frame: Week 15 to Week 40
description: Number and severity of adverse events
measure: Electrocardiogram (ECG)
time frame: Week 15 to Week 40
description: Changes in electrical activity of heartbeat measured by electrocardiogram
measure: Beck Depression Inventory (BDI) score
time frame: Week 15 to Week 40
description: Assessment of change in depression using Beck Depression Inventory (BDI) score
measure: Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS)
time frame: Week 15 to Week 40
description: Assessment of changes in impulsive-compulsive disorders using QUIP_RS
measure: Montreal cognitive assessment (MoCA)
time frame: Week 15 to Week 40
description: Assessment of change in cognitive domains using MoCA test
measure: Physical examination
time frame: Week 15 to Week 40
description: Changes in anatomic findings found in physical examination
measure: Vital signs
time frame: Week 15 to Week 40
description: Changes in vital signs
measure: Clinical laboratory safety screen
time frame: Week 15 to Week 40
description: Changes in clinical laboratory variables (chemistry, haematology, urinanalysis)
measure: Formation of anti-CDNF antibodies
time frame: Week 15 to Week 40
description: Change in anti-CDNF antibody concentration
measure: Device related changes in safety measures
time frame: Week 8 to Week 40
description: 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.
measure: Device related accuracy of implantation
time frame: Week 8
description: 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.
measure: UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score
time frame: Week 15 to Week 40
description: Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores
measure: TUG (Timed Up and Go) test
time frame: Week 15 to Week 40
description: Changes in mobility assessed by TUG test
measure: UPDRS Total score (Part I-IV)
time frame: Week 15 to Week 40
description: 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).
measure: Home diary score
time frame: Week 16 to Week 24
description: Change in functional status assessed by home diary score
measure: PDQ-39 (Parkinson's Disease Questionnaire) score
time frame: Week 15 to Week 40
description: Changes in health and daily activity assessed by PDQ-39 questionnaire score
measure: change in CGI (Clinical Global Impressions) scale
time frame: Week 16 to Week 40
description: • Change from baseline until end of treatment evaluation in mental status as measured by CGI scale.
measure: Occurrence of blockage
time frame: Week 11 to Week 36
description: Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure
measure: Cessation of infusions
time frame: Week 11 to Week 36
description: Cessation of infusions in an individual patient
measure: DAT (dopamine transporter)-PET imaging
time frame: Week 14 to Week 38
description: Change in caudate and putamen DAT availability using PET imaging.
measure: alpha-synuclein levels
time frame: Week 15 to Week 40
description: Changes in serum and CSF (cerebrospinal fluid) concentrations of various α-synuclein species
measure: Distribution of CDNF
time frame: Week 24 and Week 36
description: Level of distribution of CDNF in serum and Cmax of CDNF in CSF
measure: Daily activity measurement
time frame: Week 16 to Week 40
description: Change in daily activity measured by Parkinson's KinetiGraph™ (PKG™) Data Logger
measure: Coverage of infusate
time frame: Week 11 to Week 36
description: Coverage of the infusate in target anatomy assessed by MRI (Magnetic resonance imaging)
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients randomized to this group will receive 6 monthly infusions of placebo/vehicle
arm group label: CDNF mid-dose
arm group type: Experimental
description: Patients randomized to this group will receive 6 doses of CDNF titrated to mid-dose
arm group label: CDNF high-dose
arm group type: Experimental
description: Patients randomized to this group will receive 6 doses of CDNF titrated to high-dose
intervention type: Drug
intervention name: Cerebral Dopamine Neurotrophic Factor
description: Repeated intracerebral infusions
arm group label: CDNF high-dose
arm group label: CDNF mid-dose
arm group label: Placebo
other name: CDNF
intervention type: Device
intervention name: Renishaw Drug Delivery System
description: Stereotactically implanted device
arm group label: CDNF high-dose
arm group label: CDNF mid-dose
arm group label: Placebo
other name: DDS
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: No
last name: Per Svenningsson, MD
role: Principal Investigator
affiliation: Karolinska University Hospital
facility: 
facility: 
facility: 
country: Finland
country: Sweden
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Nervous System Diseases
mesh term: Movement Disorders
mesh term: Neurodegenerative Diseases
mesh term: Brain Diseases
mesh term: Dopamine
sharing ipd: No