Parkinson DiseasePhase 1/2NCT03775538
Safety of CDNF by Brain Infusion in Patients With Parkinson's Disease. Extension to HP-CD-CL-2002 Clinical Study
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.
Trial summary
This study is an extension to the HP-CD-CL-2002 clinical study. It evaluates the long-term 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). Long-term safety of the DDS is also being evaluated. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Parkinson Disease, Movement Disorders, Neuro-Degenerative Disease
- What is being tested?
- Cerebral Dopamine Neurotrophic Factor and Renishaw Drug Delivery System
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 5 Jul 2018to 8 Jul 2020
- 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
- Completion of 6 months treatment period in the Main study (HP-CD-CL-2002) including End-of-Study assessment
- Negative pregnancy test at study entry for females of childbearing potential. Willingness of using a highly effective form of contraception until 30 days after end of study. Males: willingness to use condom and not to donate sperm for 3 months following DAT-PET. Willingness of female partners of male study participants to use highly effective form of contraception until 30 days after their male partner's end of the study.
- At least one functioning catheter in each putamen
- Provision of informed consent
Who cannot join
- Drug-resistant rest tremor, severe dyskinesia or severe head tremor, which could interfere with treatment infusions
- Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsy, CSF shunt or other implanted central nervous system device
- Changes in pathology which give rise to safety concern such as sequelae from catheter implantation, clinically significant intracerebral trauma, oedema, haemorrhage, or infection
- Current psychosis requiring therapy
- Presence of clinically significant impulse control disorder by a positive screen on the QUIP-RS questionnaire score >20, or, presence of dopamine dysregulation syndrome
- An unresolved intolerable adverse event or adverse device event in study HP-CD-CL-2002, which is not expected to resolve or cease to an acceptable level of intensity within reasonable time
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- Medical conditions, which might impair outcome measure assessments or safety measures
- Impaired renal function
- Concomitant treatment with neuroleptics or antipsychotic medication prescribed for treatment of current psychosis, central dopamine blockers or tricyclic antidepressants
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
Stockholm, 14186
About this study
Official title: A Randomised, Double-Blind, Multi-centre, Active Treatment, Extension and Safety Study for Patients With Idiopathic Parkinson's Disease (PD) Who Previously Completed the CDNF/DDS Main Study HP-CD-CL-2002
This study is an extension to the HP-CD-CL-2002 clinical study. It evaluates the long-term 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). Long-term safety of the DDS is also being evaluated. All patients will receive monthly infusions of either mid- or high-dose of CDNF for a period of 6 months.
Read the detailed description
A patient's participation in the study will last for six months and will include nine visits:
Screening (1 visit, same as HP-CD-CL-2002 End-of-Study visit) Dosing visits: CDNF (6 visits) DAT-PET (1 visit) End-of-study visit (1 visit)
Study examinations and assessments
- Physical examination: pulse rate, blood pressure, temperature, body weight and height, body mass index (BMI), neurological exam
- ECG (electrocardiography) and blood and urine tests
- 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 movement recording device
- 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)
For more information: https://treater.eu/clinical-study/
- Conditions
- Parkinson Disease, Movement Disorders, Neuro-Degenerative Disease, Nervous System Diseases, Brain Diseases
- Being tested
- Cerebral Dopamine Neurotrophic Factor, Renishaw Drug Delivery System
- Keywords
- Parkinson, CDNF, Drug Delivery System, Intracerebral
- Medical subject headings
- Parkinson Disease, Movement Disorders, 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 group | Role | What they receive |
|---|---|---|
| CDNF mid-dose (400 micrograms) | Experimental | Patients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to mid-dose (400 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen. Receives: Drug: Cerebral Dopamine Neurotrophic Factor; Device: Renishaw Drug Delivery System |
| CDNF high-dose (1200 micrograms) | Experimental | Patients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to high-dose (1200 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen. 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.
Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
Total number, causality and severity of adverse events at any time during the study period
Measured: Week 40 to Week 65
Change in Electrocardiogram (ECG): Ventricular rate, PR interval, qRS duration, QT, QTc [safety-tolerability]
Changes in electrical activity of heartbeat measured by electrocardiogram: Ventricular rate (bpm), PR interval (msec), QRS duration (msec), QT (msec), QTc (msec)
Measured: Week 40, Week 53 and Week 65
Change in Beck Depression Inventory (BDI) score [safety-tolerability]
Assessment of change in depression using Beck Depression Inventory (BDI) score: Sadness: Pessimism; Past Failure; Loss of pleasure; Guilty feelings; Punishment Feelings; Self-dislike; Self-criticalness;Suicidal thoughts or wishes; Crying; Agitation; Loss of interest; Indecisiveness;Worthlessness; Loss of energy; Changes in sleeping pattern; Irritability; Changes in appetite; Concentration difficulty; Tiredness or fatique; Loss of interest in sex. Rated on a 4-point scale ranging from 0 to 3 based on severity of each item (0=low intensity; 3=highest intensity). The maximum total score is 63.
Measured: Week 40, Week 53 and Week 65
Change in Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [safety-tolerability]
Assessment of changes in impulsive-compulsive disorders using QUIP_RS. Questions scored 0-4 (0=never; 4=very often) on gambling, sex, buying, eating, performing tasks/hobbies, repeating simple activities, and taking Parkinson's disease medication. Total QUIP-RS Score 0-112
Measured: Week 40, Week 53 and Week 65
Change in Montreal cognitive assessment (MoCA) [safety-tolerability]
Assessment of change in cognitive domains using MoCA test: attention and, concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points; a score of 26 or above is considered normal.
Measured: Week 40, Week 53 and Week 65
Changes in physical examination: anatomic findings [safety-tolerability]
Changes in anatomic findings found in physical examination of the following body systems: general inspection/upper extremities; head, eyes, ears, nose, throat, and superficial cervial lymph notes; neck, shoulders, back; chest and lungs; cardiovascular; abdomen; lower extremities
Measured: Week 40 and Week 65
Changes in physical examination: clinical standard neurological examination
A clinical standard neurological examination by study investigator. Changes in motor function, sensory function, cranial nerve function (visual fields), cortical functions and reflexes are followed in the examination, scored as normal - abnormal without clinical relevance - abnormal with clinical relevance
Measured: Week 40 and Week 65
Changes in vital signs: blood pressure [safety-tolerability]
Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)
Measured: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in vital signs: pulse rate [safety-tolerability]
Changes in pulse rate during the study (in beats per minute)
Measured: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in vital signs: body temperature [safety-tolerability]
Changes in body temperature during the study (in degrees celsius)
Measured: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in vital signs: body weight [safety-tolerability]
Changes in body weight during the study (in kilograms)
Measured: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in vital signs: body mass index (BMI) [safety-tolerability]
Changes in body mass index during the study (in kg/m^2)
Measured: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in clinical laboratory safety screen: clinical chemistry [safety-tolerability]
Changes in laboratory variables for clinical chemistry (Na, K, Urea, creatinine, creatine kinase, Ca, Bilirubin, IgG, Albumin, ALP, ALT, AST)
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: haematology - hemoglobin [safety-tolerability]
Changes in laboratory variables for haematology: hemoglobin (g/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: haematology - hematocrit [safety-tolerability]
Changes in laboratory variables for haematology: hematocrit (%, ratio of red blood cell volume to total blood volume). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: haematology - red blood cell (RBC) count [safety-tolerability]
Changes in laboratory variables for haematology: RBC count (10E12/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: mean cell volume (MCV) of red blood cells [safety-tolerability]
Changes in laboratory variables for haematology: MCV of red blood cells (fL). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: mean cell hemoglobin of RBC (MHC) [safety-tolerability]
Changes in laboratory variables for haematology: MCH (pg). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: Platelet count [safety-tolerability]
Changes in laboratory variables for haematology: Platelet count (10E9/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: white blood cell (WBC) counts [safety-tolerability]
Changes in laboratory variables for haematology: Cell counts (10E9/L) for total WBC, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [safety-tolerability]
Changes in laboratory variables for haematology: aPTT (sec) . Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [safety-tolerability]
Changes in laboratory variables for haematology: INR (standardized prothrombin time) to determine the effects of oral anticoagulants on the clotting system. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in clinical laboratory safety screen: urinanalysis [safety-tolerability]
Changes in laboratory variables for urinanalysis (blood/erythrocytes, glucose, ketones, leukocytes, nitrites, pH, protein) studied by dipstick and scored 0-3. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Measured: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Formation of anti-CDNF antibodies [safety-tolerability]
Formation and change in anti-CDNF antibody concentration (in ng/ml).
Measured: Weeks 40, 45, 49, 53, 57, 61, and 65
Device related occurrence of adverse device effects [safety-tolerability]
Occurrence of adverse device effects (ADE) at any time of the study period, 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 40 to Week 65
Secondary outcomes (8)
Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy]
Changes in severity of PD (Parkinson's disease) motor symptoms assessed by UPDRS Part III motor scores (each scored 0-4; 0=none, 4=severe): Speech; facial expression; tremor a rest; Tremor of hands; rigidity; firger taps; hand movelents; alternating movement of hands; leg agility; rising from chair; posture; gait; postural stability; body bradykinesia and hypokinesia. The total score, the sum of scores received from 27 assessments, is 0 - 108
Measured: Week 40, Week 53 and Week 65
Change in TUG (Timed Up and Go) test [efficacy]
Changes in mobility assessed by TUG test (in minutes and seconds).
Measured: Week 40, Week 53 and Week 65
Change in UPDRS Total score (Part I-IV) [efficacy]
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): Part 1 (scored 0-16) Mentation, behaviour and mood. Part 2 (scored 0-52) Activities of daily living. Part 3 (scored 0-108) Motor examination. Part 4 (scored 0-23) Complications of therapy. The total score is 0-199 (0=totally healthy; 199=worst possible).
Measured: Week 40, Week 53 and Week 65
Change in home diary score [efficacy]
Change in functional status of the patient's dyskinesias assessed by home diary score for three-day period. Each half hour is scored: sleep, OFF, ON without dyskinesias, ON with non-troublesome dyskinesias, ON with troublesome dyskinesias. The total time in each state over 3 days is recorded (in hours). The total "bad time" is defined as "OFF time" and "ON time with troublesome dyskinesia". The total "good time" is defined as "ON time without dyskinesia" or "ON time with non-troublesome dyskinesia".
Measured: Weeks 40, 45, 49, 49, 53, 57, 61 and 65
Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy]
Changes in health and daily activity assessed by a self-administered PDQ-39 questionnaire comprising of 39 questions related to eight key areas of health in Parkinson's patients: mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication and bodily discomfort. Each question is evaluated on a scale of five terms "Never", "Occasionally", "Sometimes", "Often" or "Always or cannot do at all".
Measured: Week 40, Week 53 and Week 65
Change in CGI-I (Clinical Global Impression - Improvement) scale [efficacy]
Change in mental status as measured by CGI-I scale rated by the clinical on a seven-point scale 1-7 (1=very much improved, 4=no change, 7=very much worse).
Measured: Weeks 40, 45, 49, 53, 57, 61 and 65
Occurrence of blockage [performance assessment]
Occurrence of blockage of implanted catheter preventing or limiting infusion assessed by measuring catheter pressure at the infusion pump during infusion (in mmHg).
Measured: Week 41, 45, 49, 53, 57 and Week 61
Stability of transcutaneous port: Inability to start infusion due to connectivity problem in Drug Delivery System
The stability of transcutaneous port is evaluated by recording the cases when the infusion in an individual patient has not been able to start due to connectivity problem between the external infusion set and the transcutaneous port.
Measured: Week 41 to Week 61
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2018
- Study start5 Jul 2018
- Primary completion8 Jul 2020
- Study completion8 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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, Active Treatment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herantis Pharma Plc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Renishaw plc.
- Responsible party
- Sponsor
- Investigators
- Per Svenningsson, MD, Prof., Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03775538
- Sponsor's protocol ID
- HP-CD-CL-2003
- Status last verified
- Jan 2020
- First submitted
- 11 Oct 2018
- Last updated
- 12 Aug 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
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-Blind, Multi-centre, Active Treatment, Extension and Safety Study for Patients With Idiopathic Parkinson's Disease (PD) Who Previously Completed the CDNF/DDS Main Study HP-CD-CL-2002
- ClinicalTrials.gov ID
- NCT03775538
- Acronym / sponsor ID
- HP-CD-CL-2003
- Conditions
- Parkinson Disease, Movement Disorders, Neuro-Degenerative Disease, Nervous System Diseases, Brain Diseases
- Keywords
- Parkinson, CDNF, Drug Delivery System, Intracerebral
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Herantis Pharma Plc.Industry (pharma, biotech, devices)
- Collaborators
- Renishaw plc.
- Study start
- 5 Jul 2018 (actual)
- Primary completion
- 8 Jul 2020 (actual)
- Study completion
- 8 Jul 2020 (actual)
- First posted
- 14 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an extension to the HP-CD-CL-2002 clinical study. It evaluates the long-term 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). Long-term safety of the DDS is also being evaluated. All patients will receive monthly infusions of either mid- or high-dose of CDNF for a period of 6 months.
Detailed description
A patient's participation in the study will last for six months and will include nine visits:
Screening (1 visit, same as HP-CD-CL-2002 End-of-Study visit) Dosing visits: CDNF (6 visits) DAT-PET (1 visit) End-of-study visit (1 visit)
Study examinations and assessments
- Physical examination: pulse rate, blood pressure, temperature, body weight and height, body mass index (BMI), neurological exam
- ECG (electrocardiography) and blood and urine tests
- 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 movement recording device
- 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)
For more information: https://treater.eu/clinical-study/
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised, Double-Blind, Active Treatment
| Arm | Type | Receives |
|---|---|---|
| CDNF mid-dose (400 micrograms) | Experimental | Drug: Cerebral Dopamine Neurotrophic Factor, Device: Renishaw Drug Delivery SystemPatients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to mid-dose (400 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen. |
| CDNF high-dose (1200 micrograms) | Experimental | Drug: Cerebral Dopamine Neurotrophic Factor, Device: Renishaw Drug Delivery SystemPatients randomized to this group will receive 6 monthly-intermittent intracerebral doses of Cerebral Dopamine Neurotrophic Factor (CDNF) titrated to high-dose (1200 micrograms) administered via the Renishaw Drug Delivery System (DDS) to the bilateral putamen. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Completion of 6 months treatment period in the Main study (HP-CD-CL-2002) including End-of-Study assessment
- Negative pregnancy test at study entry for females of childbearing potential. Willingness of using a highly effective form of contraception until 30 days after end of study. Males: willingness to use condom and not to donate sperm for 3 months following DAT-PET. Willingness of female partners of male study participants to use highly effective form of contraception until 30 days after their male partner's end of the study.
- At least one functioning catheter in each putamen
- Provision of informed consent
Key exclusion criteria (9 listed)
- Drug-resistant rest tremor, severe dyskinesia or severe head tremor, which could interfere with treatment infusions
- Significant neurological disorder other than PD including clinically significant head trauma, cerebrovascular disease, epilepsy, CSF shunt or other implanted central nervous system device
- Changes in pathology which give rise to safety concern such as sequelae from catheter implantation, clinically significant intracerebral trauma, oedema, haemorrhage, or infection
- Current psychosis requiring therapy
- Presence of clinically significant impulse control disorder by a positive screen on the QUIP-RS questionnaire score >20, or, presence of dopamine dysregulation syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cerebral Dopamine Neurotrophic FactorAlso: CDNFRepeated intracerebral infusions | Drug | CDNF high-dose (1200 micrograms), CDNF mid-dose (400 micrograms) |
| Renishaw Drug Delivery SystemAlso: DDSStereotactically implanted device | Device | CDNF high-dose (1200 micrograms), CDNF mid-dose (400 micrograms) |
Primary outcome
Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
Time frame: Week 40 to Week 65
Total number, causality and severity of adverse events at any time during the study period
Change in Electrocardiogram (ECG): Ventricular rate, PR interval, qRS duration, QT, QTc [safety-tolerability]
Time frame: Week 40, Week 53 and Week 65
Changes in electrical activity of heartbeat measured by electrocardiogram: Ventricular rate (bpm), PR interval (msec), QRS duration (msec), QT (msec), QTc (msec)
Change in Beck Depression Inventory (BDI) score [safety-tolerability]
Time frame: Week 40, Week 53 and Week 65
Assessment of change in depression using Beck Depression Inventory (BDI) score: Sadness: Pessimism; Past Failure; Loss of pleasure; Guilty feelings; Punishment Feelings; Self-dislike; Self-criticalness;Suicidal thoughts or wishes; Crying; Agitation; Loss of interest; Indecisiveness;Worthlessness; Loss of energy; Changes in sleeping pattern; Irritability; Changes in appetite; Concentration difficulty; Tiredness or fatique; Loss of interest in sex. Rated on a 4-point scale ranging from 0 to 3 based on severity of each item (0=low intensity; 3=highest intensity). The maximum total score is 63.
Change in Questionnaire for impulsive-compulsive disorder in Parkinson's disease rating scale (QUIP_RS) [safety-tolerability]
Time frame: Week 40, Week 53 and Week 65
Assessment of changes in impulsive-compulsive disorders using QUIP_RS. Questions scored 0-4 (0=never; 4=very often) on gambling, sex, buying, eating, performing tasks/hobbies, repeating simple activities, and taking Parkinson's disease medication. Total QUIP-RS Score 0-112
Change in Montreal cognitive assessment (MoCA) [safety-tolerability]
Time frame: Week 40, Week 53 and Week 65
Assessment of change in cognitive domains using MoCA test: attention and, concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The total possible score is 30 points; a score of 26 or above is considered normal.
Changes in physical examination: anatomic findings [safety-tolerability]
Time frame: Week 40 and Week 65
Changes in anatomic findings found in physical examination of the following body systems: general inspection/upper extremities; head, eyes, ears, nose, throat, and superficial cervial lymph notes; neck, shoulders, back; chest and lungs; cardiovascular; abdomen; lower extremities
Changes in physical examination: clinical standard neurological examination
Time frame: Week 40 and Week 65
A clinical standard neurological examination by study investigator. Changes in motor function, sensory function, cranial nerve function (visual fields), cortical functions and reflexes are followed in the examination, scored as normal - abnormal without clinical relevance - abnormal with clinical relevance
Changes in vital signs: blood pressure [safety-tolerability]
Time frame: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)
Changes in vital signs: pulse rate [safety-tolerability]
Time frame: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in pulse rate during the study (in beats per minute)
Changes in vital signs: body temperature [safety-tolerability]
Time frame: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in body temperature during the study (in degrees celsius)
Changes in vital signs: body weight [safety-tolerability]
Time frame: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in body weight during the study (in kilograms)
Changes in vital signs: body mass index (BMI) [safety-tolerability]
Time frame: Weeks 41, 45, 49, 53, 57, 61, and 63
Changes in body mass index during the study (in kg/m^2)
Changes in clinical laboratory safety screen: clinical chemistry [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for clinical chemistry (Na, K, Urea, creatinine, creatine kinase, Ca, Bilirubin, IgG, Albumin, ALP, ALT, AST)
Changes in clinical laboratory safety screen: haematology - hemoglobin [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: hemoglobin (g/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: haematology - hematocrit [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: hematocrit (%, ratio of red blood cell volume to total blood volume). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: haematology - red blood cell (RBC) count [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: RBC count (10E12/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: mean cell volume (MCV) of red blood cells [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: MCV of red blood cells (fL). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: mean cell hemoglobin of RBC (MHC) [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: MCH (pg). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: Platelet count [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: Platelet count (10E9/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: white blood cell (WBC) counts [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: Cell counts (10E9/L) for total WBC, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: activated partial thromboplastin time (aPTT) [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: aPTT (sec) . Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: International Normalized Ratio (INR) [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for haematology: INR (standardized prothrombin time) to determine the effects of oral anticoagulants on the clotting system. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Changes in clinical laboratory safety screen: urinanalysis [safety-tolerability]
Time frame: Weeks 40, 41, 45, 49, 53, 57, 61, and 65
Changes in laboratory variables for urinanalysis (blood/erythrocytes, glucose, ketones, leukocytes, nitrites, pH, protein) studied by dipstick and scored 0-3. Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".
Formation of anti-CDNF antibodies [safety-tolerability]
Time frame: Weeks 40, 45, 49, 53, 57, 61, and 65
Formation and change in anti-CDNF antibody concentration (in ng/ml).
Device related occurrence of adverse device effects [safety-tolerability]
Time frame: Week 40 to Week 65
Occurrence of adverse device effects (ADE) at any time of the study period, 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.
8 secondary outcomes
Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy]
Time frame: Week 40, Week 53 and Week 65
Change in TUG (Timed Up and Go) test [efficacy]
Time frame: Week 40, Week 53 and Week 65
Change in UPDRS Total score (Part I-IV) [efficacy]
Time frame: Week 40, Week 53 and Week 65
Change in home diary score [efficacy]
Time frame: Weeks 40, 45, 49, 49, 53, 57, 61 and 65
Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy]
Time frame: Week 40, Week 53 and Week 65
Change in CGI-I (Clinical Global Impression - Improvement) scale [efficacy]
Time frame: Weeks 40, 45, 49, 53, 57, 61 and 65
Occurrence of blockage [performance assessment]
Time frame: Week 41, 45, 49, 53, 57 and Week 61
Stability of transcutaneous port: Inability to start infusion due to connectivity problem in Drug Delivery System
Time frame: Week 41 to Week 61
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2020.
- Derived from this study: PubMed 38072889Singh 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Svenningsson, MD, Prof. principal investigator
Karolinska University Hospital
3 sites in 2 countries: see every site and its status.
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 4 inclusion and 9 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 12 Aug 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. 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?
Incidence of treatment-emergent adverse events (AEs)[safety-tolerability] (time frame: Week 40 to Week 65). The study lists 25 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 NCT03775538, 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 12 Aug 2020.