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Parkinson DiseasePhase 1/2NCT03295786

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

A Phase 1/2 study testing Cerebral Dopamine Neurotrophic Factor and Renishaw Drug Delivery System in people with Parkinson Disease and Movement Disorders, run by Herantis Pharma Plc. at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 35 to 75 years
What is being tested?
Cerebral Dopamine Neurotrophic Factor and Renishaw Drug Delivery System
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
17 participants
Where
3 sitesin 2 countries
Study dates
26 Sep 2017to 19 Dec 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 35 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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
  • History of drug or alcohol abuse within 2 years of screening
  • Use of any investigational drug or device within 90 days of screening
  • Active breastfeeding

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

Sweden2 sites

  • Skåne University Hospital

    Lund, 221 85

  • Karolinska University Hospital, Huddinge

    Stockholm, 141 86

Other trials in Sweden

Finland1 site

  • Helsinki University Hospital

    Helsinki, 00029

Other trials in Finland

About this study

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

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.

Read the 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/

Being tested
Cerebral Dopamine Neurotrophic Factor, Renishaw Drug Delivery System
Keywords
Parkinson, CDNF, Drug Delivery System, Intracerebral
Medical subject headings
Parkinson Disease, Movement Disorders, Neurodegenerative Diseases, Nervous System Diseases, Brain Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cerebral Dopamine Neurotrophic FactorDrug

    Also called CDNF

    Repeated intracerebral infusions

  • Renishaw Drug Delivery SystemDevice

    Also called DDS

    Stereotactically implanted device

Study groups in NCT03295786
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPatients randomized to this group will receive 6 monthly infusions of placebo/vehicle
Receives: Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System
CDNF mid-doseExperimentalPatients randomized to this group will receive 6 doses of CDNF titrated to mid-dose
Receives: Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System
CDNF high-doseExperimentalPatients randomized to this group will receive 6 doses of CDNF titrated to high-dose
Receives: Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Adverse events (AEs)

    Number and severity of adverse events

    Measured: Week 15 to Week 40

  2. Electrocardiogram (ECG)

    Changes in electrical activity of heartbeat measured by electrocardiogram

    Measured: Week 15 to Week 40

  3. Beck Depression Inventory (BDI) score

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

    Measured: Week 15 to Week 40

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

    Assessment of changes in impulsive-compulsive disorders using QUIP_RS

    Measured: Week 15 to Week 40

  5. Montreal cognitive assessment (MoCA)

    Assessment of change in cognitive domains using MoCA test

    Measured: Week 15 to Week 40

  6. Physical examination

    Changes in anatomic findings found in physical examination

    Measured: Week 15 to Week 40

  7. Vital signs

    Changes in vital signs

    Measured: Week 15 to Week 40

  8. Clinical laboratory safety screen

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

    Measured: Week 15 to Week 40

  9. Formation of anti-CDNF antibodies

    Change in anti-CDNF antibody concentration

    Measured: Week 15 to Week 40

  10. 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.

    Measured: Week 8 to Week 40

  11. 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.

    Measured: Week 8

Secondary outcomes (8)

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

    Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores

    Measured: Week 15 to Week 40

  2. TUG (Timed Up and Go) test

    Changes in mobility assessed by TUG test

    Measured: Week 15 to Week 40

  3. UPDRS Total score (Part I-IV)

    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).

    Measured: Week 15 to Week 40

  4. Home diary score

    Change in functional status assessed by home diary score

    Measured: Week 16 to Week 24

  5. PDQ-39 (Parkinson's Disease Questionnaire) score

    Changes in health and daily activity assessed by PDQ-39 questionnaire score

    Measured: Week 15 to Week 40

  6. change in CGI (Clinical Global Impressions) scale

    • Change from baseline until end of treatment evaluation in mental status as measured by CGI scale.

    Measured: Week 16 to Week 40

  7. Occurrence of blockage

    Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure

    Measured: Week 11 to Week 36

  8. Cessation of infusions

    Cessation of infusions in an individual patient

    Measured: Week 11 to Week 36

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2017
  2. Study start26 Sep 2017
  3. Primary completion19 Dec 2019
  4. Study completion19 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomised, Double-Blind, Placebo Controlled
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03295786
Sponsor's protocol ID
HP-CD-CL-2002
Other IDs
2015-004175-73, 2015
Status last verified
Jan 2020
First submitted
14 Sep 2017
Last updated
13 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Singh A, Panhelainen A, Reunanen S, Luk KC, Voutilainen MH. Combining fibril-induced alpha-synuclein aggregation and 6-hydroxydopamine in a mouse model of Parkinson's disease and the effect of cerebral dopamine neurotrophic factor on the induced neurodegeneration. Eur J Neurosci. 2024 Jan;59(1):132-153. doi: 10.1111/ejn.16196. Epub 2023 Dec 10.

    PubMed 38072889

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cerebral Dopamine Neurotrophic Factor and Renishaw Drug Delivery System in people with Parkinson Disease and Movement Disorders, run by Herantis Pharma Plc. at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Sweden, Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse events (AEs) (time frame: Week 15 to Week 40). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03295786, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.

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