Exenatide Once Weekly Over 2 Years as a Potential Disease Modifying Treatment for Parkinson's Disease

Phase 3

Active, not recruiting

• Conditions: Parkinson's Disease
• Interventions: Drug: Exenatide extended release 2mg (Bydureon)

• Registration Number: NCT04232969
• Lead Sponsor: University College, London

Brief Summary

This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, the investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period. In order to explore this, a randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide is being undertaken (Exenatide-PD3).

Detailed Description

This study is a clinical trial in patients with Parkinson's disease (PD), of a drug called exenatide, which is already licensed for the treatment of patients with type 2 diabetes. There have been several groups that have confirmed that exenatide has beneficial effects of nerve cells when tested in the laboratory, which raises the possibility that exenatide may slow down or stop the degeneration of PD. In an open label trial in patients with PD who self administered the drug for a period of 48 weeks, investigators have previously shown that the drug is well tolerated and shows encouraging effects on the movement and non-movement aspects of the disease. A double blind placebo controlled trial involving 60 participants was then conducted which indicated that exenatide may be a "neuroprotective" drug, i.e. one that stops the nerve cells dying in PD. The next step is therefore to confirm this "neuroprotective" effect and to see whether this effect can be reproduced in a multi-centre setting including a larger number of participants. An important objective is to explore whether any positive effects remain static or increase when the treatment is continued over a 96 week period.

Study Timeline

• Study First Submitted: 2020-01-10
• Study First Submitted QC: 2020-01-16
• Study First Posted: 2020-01-18
• Study Start: 2020-01-20
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-20
• Last Update Posted: 2023-12-21
• Primary Completion: 2024-02-24
• Study Completion: 2024-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 194

Inclusion Criteria

1. Diagnosis of Parkinson's disease.
2. Hoehn and Yahr stage ≤2.5 in the ON medication state.
3. Between 25 and 80 years of age.
4. On dopaminergic treatment for at least 4 weeks before enrolment.
5. Ability to self-administer, or to arrange carer administration of trial medication.
6. Documented informed consent to participate.

Exclusion Criteria

1. Diagnosis or suspicion of other cause for Parkinsonism.
2. Patients unable to attend the clinic visits in the practically defined OFF medication state.
3. Body mass index <18.5.
4. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
5. Significant cognitive impairment defined by a score <21 on the Montreal Cognitive Assessment.
6. Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).
7. Prior intra-cerebral surgical intervention for Parkinson's disease.
8. Previous participation in one of the following Parkinson's disease trials (Biogen SPARK trial, Prothena Pasadena trial, Sanofi Genzyme MOVES-PD trial, UDCA-PD UP Study or any other trial still considered to involve a potentially PD modifying agent).
9. Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days
10. Previous exposure to exenatide.
11. Impaired renal function with creatinine clearance <50ml/min.
12. History of pancreatitis.
13. Type 1 or Type 2 diabetes mellitus.
14. Severe gastrointestinal disease (e.g. gastroparesis)
15. Hyperlipidaemia.
16. History or family history of medullary thyroid cancer (MTC).
17. Multiple endocrine neoplasia 2 (MEN2) syndrome.
18. Hypersensitivity to any of exenatide's excipients.
19. Females that are pregnant or breast feeding.
20. WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire trial period and up to 3 months after the last dose of trial medication.
21. Participants who lack the capacity to give informed consent
22. Any medical or psychiatric condition or previous conventional/experimental treatment which in the investigator's opinion compromises the potential participant's ability to participate.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Exenatide	Exenatide extended release 2mg (Bydureon)	Exenatide extended release 2mg (Bydureon) once weekly for 96 weeks n=100
Placebo	Exenatide extended release 2mg (Bydureon)	Exenatide extended release placebo once weekly for 96 weeks n=100

Primary Outcome Measures

Name	Time	Method
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3	96 weeks	Comparison of MDS-UPDRS part 3 motor sub-score in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Min value- 0 Max Value- 108. Higher score indicative of worse outcome.

Secondary Outcome Measures

Name	Time	Method
Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1,2, and 4 ON medication scores.	96 weeks	Questionnaire. Section I: 16 points; Section II: 52; Section IV: 23. Higher score indicative of worse outcome.
Timed Walk assessment ON and OFF medication	96 weeks	Assessment with research team
Montreal Cognitive Assessment	96 weeks	Questionnaire. Maximum Score= 30. Lower scores indicative of worse outcome.
Unified Dyskinesia Rating Scale (UDysRS)	96 weeks	Questionnaire. The UDysRS has four parts: I: Historical Disability (patient perceptions) of On-Dyskinesia impact (maximum 44 points); II: Historical Disability (patient perceptions) of Off-Dystonia impact (maximum 16 points); III: Objective Impairment (dyskinesia severity, anatomical distribution over seven body regions, and type (choreic or dystonic) based on four activities observed or video-recorded (28 points); IV: Objective Disability based on Part III activities (maximum 16 points). Higher scores= worse outcomes
Safety and tolerability of exenatide as indicated by changes in Neutrophils (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Eosinophils (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Basophils (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Lymphocytes (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Monocytes (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Prothrombin Time (secs)	96 weeks	Blood Tests (Coagulation)
Patient Health Questionnaire-9 (PHQ-9)	96 weeks	Questionnaire. Depression Severity: 0-4 none, 5-9 mild, 10-14 moderate, 15-19 moderately severe, 20-27 severe. Max Score= 27. Higher Score= worse outcome
Safety and tolerability of exenatide as indicated by changes in pulse (bpm)	96 weeks	Vital Signs
Parkinson's Disease 39 item Quality of life questionnaire	96 weeks	This questionnaire assesses how often people affected by Parkinson's experience difficulties across 8 dimensions of daily living. The 39 item questionnaire offers a patient reported measure of health status and quality of life and is the most frequently used disease-specific health status measure. Higher score= worse outcome.
Non-Motor Symptoms Scale (NMSS)	96 weeks	Questionnaire. The Non-Motor Symptoms Scale (NMSS) is a 30-item rater-based scale to assess a wide range of non-motor symptoms in patients with Parkinson's disease (PD). The NMSS measures the severity and frequency of non-motor symptoms across nine dimensions. The scale can be used for patients at all stages of PD. Higher score indicative of worse outcome. NMSS total score is 0 to 360.
Levodopa Equivalent Dose	96 weeks	Assessment with Research Team
3 day Hauser diary of Parkinson's Disease State	96 weeks	Participant take Home questionnaire. (Time-On, Off, Non troublesome Dyskinesia, Troublesome dyskinesia, Asleep). Higher total scores indicate more severe motor signs of Parkinson's.
Safety and tolerability of exenatide as indicated by changes in blood pressure (mmHg)	96 weeks	Vital Signs
Safety and tolerability of exenatide as indicated by changes in Body Mass Index (weight and height will be combined to report BMI in kg/m^2)	96 weeks	Vital Signs
Safety and tolerability of exenatide as indicated by changes in Red Blood Cell Count (10^12/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in White Blood Cell Count (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Haemoglobin (g/dL)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Haematocrit (%)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in Platelets (10^9/L)	96 weeks	Full Blood Count
Safety and tolerability of exenatide as indicated by changes in International Normalized Ratio (Calculated from Prothrombin Time)	96 weeks	Blood Tests (Coagulation)
Safety and tolerability of exenatide as indicated by changes in Activated Partial Thromboplastin Time (secs)	96 weeks	Blood Tests (Coagulation)
Safety and tolerability of exenatide as indicated by changes in Thrombin Time (secs)	96 weeks	Blood Tests (Coagulation)
Safety and tolerability of exenatide as indicated by changes in Potassium (mmol/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Urea (mmol/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Aspartate Aminotransferase (IU/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Fibrinogen (g/L)	96 weeks	Blood Tests (Coagulation)
Safety and tolerability of exenatide as indicated by changes in Glycated Haemoglobin (% of Haemoglobin)	96 weeks	Blood Tests (Blood Sugar Levels / Diabetes Testing)
Safety and tolerability of exenatide as indicated by changes in Sodium (mmol/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Creatinine (µmol/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Creatinine Clearance (ml/min)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Total Bilirubin (µmol/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Alkaline phosphatase (IU/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Alanine transaminase (IU/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Triglycerides (mg/dL)	96 weeks	Biochemistry (Fasting)
Safety and tolerability of exenatide as indicated by changes in Cholesterol (mg/dL)	96 weeks	Biochemistry (Fasting)
Safety and tolerability of exenatide as indicated by changes in Glucose (mmol/L)	96 weeks	Biochemistry (Fasting)
Safety and tolerability of exenatide as indicated by changes in Serum Amylase (U/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Thyroid Stimulating Hormone (mIU/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Thyroxin (T4) (pmol/L)	96 weeks	Biochemistry
Safety and tolerability of exenatide as indicated by changes in Insulin (IU/L)	96 weeks	Biochemistry (Fasting)
Safety and tolerability of exenatide as indicated by the occurrence / severity of Adverse Events	96 weeks	Ongoing Safety Reporting

Trial Locations

Locations (1)

University College London Hospital; 🇬🇧 London, United Kingdom