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

Overview

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.

Full Title of Study: “A Long-Term Follow-up Safety Study for Patients With Idiopathic Parkinson’s Disease (PD) Implanted With the DDS and/or Who Received Treatment in the Main Study and/or Extension Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: September 20, 2022

Detailed Description

A patients participation in the study will last for up to 4 years and will include up to nine visits:

- Screening (1 visit, same as HP-CD-CL-2003 End-of-Study visit)

- Pre-surgery / explantation surgery / post-surgery (3 visits)

- Safety (4 visits)

- DAT-PET (Dopamine Transporter – Positron Emission Tomography) examination (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.

- Magnetic resonance imaging (MRI)

- Positron emission tomography scans (PET)

- Skin condition over any remaining implanted subcutaneous portion of the device.

- Skin healing after port / device removal.

For more information: https://treater.eu/clinical-study/

Interventions

  • Device: Renishaw Drug Delivery System
    • 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.

Arms, Groups and Cohorts

  • Experimental: No Arm
    • As this is the follow up study, there are no arms

Clinical Trial Outcome Measures

Primary Measures

  • Incidence of treatment-emergent adverse events (AEs)[safety-tolerability]
    • Time Frame: Until study completion, up to month 58
    • Total number, causality and severity of adverse events at any time during the study period
  • Change in Electrocardiogram (ECG): Ventricular rate (bpm), [safety-tolerability]
    • Time Frame: Week 71 and Month 25
    • Changes in electrical activity of heartbeat measured by electrocardiogram: Ventricular rate (bpm),
  • Change in Electrocardiogram (ECG): PR (pulse rate) interval, qRS duration, QT, QTc (msec) [safety-tolerability]
    • Time Frame: Week 71 and Month 25
    • Changes in electrical activity of heartbeat measured by electrocardiogram: PR interval (msec), QRS duration (msec), QT (msec), QTc (msec)
  • Change in Beck Depression Inventory (BDI) score [safety-tolerability]
    • Time Frame: Week 71 and Month 25
    • 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 71 and Month 25
    • 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
  • Change in Montreal cognitive assessment (MoCA) [safety-tolerability]
    • Time Frame: Week 71 and Month 25
    • 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 71, and Months 25, 34, 58
    • 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 71, and Months 25, 34, 58
    • 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 55, 57, 58, 75
    • 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 55, 57, 58, 75
    • Changes in pulse rate during the study (in beats per minute)
  • Changes in vital signs: body temperature [safety-tolerability]
    • Time Frame: Weeks 55, 57, 58, 75
    • Changes in body temperature during the study (in degrees celcius)
  • Changes in vital signs: body weight [safety-tolerability]
    • Time Frame: Weeks 55, 57, 58, 75
    • Changes in body weight during the study (in kilograms)
  • Changes in vital signs: body mass index (BMI) [safety-tolerability]
    • Time Frame: Weeks 55, 57, 58, 75
    • 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 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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))
  • Changes in clinical laboratory safety screen: haematology – haemoglobin [safety-tolerability]
    • Time Frame: Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 – haematocrit [safety-tolerability]
    • Time Frame: Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 haemoglobin of RBC (MHC) [safety-tolerability]
    • Time Frame: Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58
    • Changes in laboratory variables for haematology: MCH (Mean cell hemoglobin) (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 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 call (WBC) count [safety-tolerability]
    • Time Frame: Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 Normalised Ratio (INR) [safety-tolerability]
    • Time Frame: Weeks 53, 55, 57, 58, 71 and Months 25, 34, 58
    • 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 53, 55, 57, 58, 71 and Month 25
    • 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 58, 78 and Month 25
    • Formation and change in anti-CDNF antibody concentration (in ng/ml).
  • Device related occurrence of adverse device effects [safety-tolerability]
    • Time Frame: Week 49 and Month 58
    • 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.

Secondary Measures

  • Change in UPDRS (Unified Parkinson’s Disease Rating Scale) Part III motor score [efficacy]
    • Time Frame: Week 71 and Month 25
    • 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
  • Change in TUG (Timed Up and Go) test [efficacy]
    • Time Frame: Week 71 and Month 25
    • Changes in mobility assessed by TUG test (in minutes and seconds).
  • Change in UPDRS Total score (Part I-IV) [efficacy]
    • Time Frame: Week 71 and Month 25
    • 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).
  • Change in home diary score [efficacy]
    • Time Frame: Weeks 40, 45, 49, 53, 57, 58, 61, 65, 71, and Month 25
    • 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”.
  • Change in PDQ-39 (Parkinson’s Disease Questionnaire) score [efficacy]
    • Time Frame: Week 71 and Month 25
    • 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”.
  • Change in CGI-I (Clinical Global Impression – Improvement) scale [efficacy]
    • Time Frame: Weeks 40, 45, 49, 53, 57, 58, 61, 65, 71, and Month 25
    • 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).
  • Healing of patient skin after port removal
    • Time Frame: Month 25, 34 and 58
    • Any Adverse Events (AEs) or Serious Adverse Events (SAEs) related to the skin condition once the port has been removed

Participating in This Clinical Trial

Inclusion Criteria

1. Completion of visit 4 (implantation of DDS) within main study HP-CD-CL-2002.

2. 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.

3. Provision of informed consent.

Exclusion Criteria

  • None

Gender Eligibility: All

Minimum Age: 35 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Renishaw
  • Collaborator
    • Herantis Pharma Plc.
  • Provider of Information About this Clinical Study
    • Sponsor

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