Long-Term Follow-up Safety After DDS Implantation With/Without CDNF Infusions

NCT04228653 | Unknown Phase 1 DMC

• 1 other identifier: HP-CD-CL-2004
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 3

Brief Summary

This study is a follow up to the HP-CD-CL-2002 clinical study. It evaluates the long-term safety in patients with Parkinson's disease after implantation of an investigational drug delivery system (DDS) with or without infusions of CDNF. All patients will have at least the port explanted.

Conditions

Parkinson Disease; Movement Disorders; Neuro-Degenerative Disease; Nervous System Diseases; Brain Diseases

Keywords

Parkinson; CDNF; Drug Delivery System; Intracerebral; Parkinson Disease; Nervous System Disease; Movement Disorders; Brain Diseases; Neurodegenerative Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Central Nervous System Diseases; Dopamine; Cardiotonic Agents; Sympathomimetrics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents

Outcome Measures

Primary Outcomes (26)

• Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]

  Total number, causality and severity of adverse events at any time during the study period

  Until study completion, up to month 58

• Change in Electrocardiogram (ECG): Ventricular rate (bpm), [safety-tolerability]

  Changes in electrical activity of heartbeat measured by electrocardiogram: Ventricular rate (bpm),

  Week 71 and Month 25

• Change in Electrocardiogram (ECG): PR (pulse rate) interval, qRS duration, QT, QTc (msec) [safety-tolerability]

  Changes in electrical activity of heartbeat measured by electrocardiogram: PR interval (msec), QRS duration (msec), QT (msec), QTc (msec)

  Week 71 and Month 25

• 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.

  Week 71 and Month 25

• 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 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 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

  Week 71 and Month 25

• 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.

  Week 71 and Month 25

• 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

  Week 71, and Months 25, 34, 58

• 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

  Week 71, and Months 25, 34, 58

• Changes in vital signs: blood pressure [safety-tolerability]

  Changes in blood pressure during the study , measured as systolic and diastolic blood pressure (in mmHg)

  Weeks 55, 57, 58, 75

• Changes in vital signs: pulse rate [safety-tolerability]

  Changes in pulse rate during the study (in beats per minute)

  Weeks 55, 57, 58, 75

• Changes in vital signs: body temperature [safety-tolerability]

  Changes in body temperature during the study (in degrees celcius)

  Weeks 55, 57, 58, 75

• Changes in vital signs: body weight [safety-tolerability]

  Changes in body weight during the study (in kilograms)

  Weeks 55, 57, 58, 75

• Changes in vital signs: body mass index (BMI) [safety-tolerability]

  Changes in body mass index during the study (in kg/m\^2)

  Weeks 55, 57, 58, 75

• 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 (Immunoglobulin G), Albumin, ALP(Alkaline phosphatase), ALT (Alanine transaminase), AST (Aspartate transaminase))

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• Changes in clinical laboratory safety screen: haematology - haemoglobin [safety-tolerability]

  Changes in laboratory variables for haematology: hemoglobin (g/L). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• Changes in clinical laboratory safety screen: haematology - haematocrit [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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• 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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• 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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• Changes in clinical laboratory safety screen: mean cell haemoglobin of RBC (MHC) [safety-tolerability]

  Changes in laboratory variables for haematology: MCH (Mean cell hemoglobin) (pg). Result evaluated as "normal", "abnormal without clinical relevance" or "abnormal with clinical relevance".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• 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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• Changes in clinical laboratory safety screen: white blood call (WBC) count [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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• 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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• Changes in clinical laboratory safety screen: International Normalised 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".

  Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58

• 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".

  Weeks 53, 55, 57, 58, 71 and Month 25

• Formation of anti-CDNF antibodies [safety-tolerability]

  Formation and change in anti-CDNF antibody concentration (in ng/ml).

  Weeks 58, 78 and Month 25

• 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.

  Week 49 and Month 58

Secondary Outcomes (7)

• Change in UPDRS (Unified Parkinson's Disease Rating Scale) Part III motor score [efficacy]

  Week 71 and Month 25

• Change in TUG (Timed Up and Go) test [efficacy]

  Week 71 and Month 25

• Change in UPDRS Total score (Part I-IV) [efficacy]

  Week 71 and Month 25

• Change in home diary score [efficacy]

  Weeks 40, 45, 49, 53, 57, 58, 61, 65, 71, and Month 25

• Change in PDQ-39 (Parkinson's Disease Questionnaire) score [efficacy]

  Week 71 and Month 25

Other Outcomes (2)

• Change in DAT (dopamine transporter)-PET imaging [exploratory]

  Week 63

• Change in daily activity measurement [exploratory]

  Weeks 58, 71 and Month 25

Study Arms (1)

No Arm

EXPERIMENTAL

As this is the follow up study, there are no arms

Device: Renishaw Drug Delivery System

Interventions

Renishaw Drug Delivery System DEVICE

Device that allows pharmaceuticals to be delivered into the brain is to be assessed over a period of time to inform of the long term safety of the implanted device.

No Arm

Eligibility Criteria

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

You may qualify if:

• Completion of visit 4 (implantation of DDS) within main study HP-CD-CL-2002.
• Patients who:
• Discontinued main study after visit 4 of main study or discontinued extension study.
• Received 6 doses in main study but didn't participate in extension study.
• Received 12 doses including extension study.
• Provision of informed consent.

You may not qualify if:

• None

Sponsors & Collaborators

• Renishaw: lead
• Herantis Pharma Plc.: collaborator

Study Sites (3)

Helsinki University Hospital

Helsinki, 00029, Finland

Location

Skåne University Hospital

Lund, 221 85, Sweden

Location

Karolinksa University Hospital

Stockholm, 14186, Sweden

Location

MeSH Terms

Conditions

Parkinson Disease; Movement Disorders; Nervous System Diseases; Brain Diseases; Neurodegenerative Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Synucleinopathies

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: January 14, 2020
• Study Start: March 20, 2019
• Primary Completion: September 20, 2022
• Study Completion: March 20, 2023
• Last Updated: March 23, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (2); FI (1)