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

NCT04232969 | Completed Phase 3 DMC

• 1 other identifier: 18/0320
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

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).

Conditions

Parkinson's Disease

Keywords

Parkinson's Disease; Exenatide; Parkinson's research

Outcome Measures

Primary Outcomes (1)

• Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part 3

  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.

  96 weeks

Secondary Outcomes (45)

• Movement Disorder Society Unified Parkinson's Disease Rating Scale part 1,2, and 4 ON medication scores.

  96 weeks

• Timed Walk assessment ON and OFF medication

  96 weeks

• Montreal Cognitive Assessment

  96 weeks

• Unified Dyskinesia Rating Scale (UDysRS)

  96 weeks

• Patient Health Questionnaire-9 (PHQ-9)

  96 weeks

Study Arms (2)

Exenatide

ACTIVE COMPARATOR

Exenatide extended release 2mg (Bydureon) once weekly for 96 weeks n=100

Drug: Exenatide extended release 2mg (Bydureon)

Placebo

PLACEBO COMPARATOR

Exenatide extended release placebo once weekly for 96 weeks n=100

Drug: Exenatide extended release 2mg (Bydureon)

Interventions

Exenatide extended release 2mg (Bydureon) DRUG

Subcutaneous Injection

Exenatide; Placebo

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Diagnosis or suspicion of other cause for Parkinsonism.
• Patients unable to attend the clinic visits in the practically defined OFF medication state.
• Body mass index \<18.5.
• Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol.
• Significant cognitive impairment defined by a score \<21 on the Montreal Cognitive Assessment.
• Concurrent severe depression defined by a score ≥16 on the Patient Health Questionnaire (PHQ-9).
• Prior intra-cerebral surgical intervention for Parkinson's disease.
• 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).
• Participation in another clinical trial of a device, drug or surgical treatment within the last 30 days
• Previous exposure to exenatide.
• Impaired renal function with creatinine clearance \<50ml/min.
• History of pancreatitis.
• Type 1 or Type 2 diabetes mellitus.
• Severe gastrointestinal disease (e.g. gastroparesis)
• Hyperlipidaemia.

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

University College London Hospital

London, United Kingdom

Location

Related Publications (2)

• Vijiaratnam N, Girges C, Auld G, McComish R, King A, Skene SS, Hibbert S, Wong A, Melander S, Gibson R, Matthews H, Dickson J, Carroll C, Patrick A, Inches J, Silverdale M, Blackledge B, Whiston J, Hu M, Welch J, Duncan G, Power K, Gallen S, Kerr J, Chaudhuri KR, Batzu L, Rota S, Jabbari E, Morris H, Limousin P, Greig N, Li Y, Libri V, Gandhi S, Athauda D, Chowdhury K, Foltynie T. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. Lancet. 2025 Feb 22;405(10479):627-636. doi: 10.1016/S0140-6736(24)02808-3. Epub 2025 Feb 4.

  PMID: 39919773 DERIVED

• Vijiaratnam N, Girges C, Auld G, Chau M, Maclagan K, King A, Skene S, Chowdhury K, Hibbert S, Morris H, Limousin P, Athauda D, Carroll CB, Hu MT, Silverdale M, Duncan GW, Chaudhuri R, Lo C, Del Din S, Yarnall AJ, Rochester L, Gibson R, Dickson J, Hunter R, Libri V, Foltynie T. Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson's disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The 'Exenatide-PD3' study. BMJ Open. 2021 May 28;11(5):e047993. doi: 10.1136/bmjopen-2020-047993.

  PMID: 34049922 DERIVED

Related Links

• Sponsor Trial web link

MeSH Terms

Conditions

Parkinson Disease

Interventions

Exenatide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Tom Foltynie

  University College London Comprehensive Clinical Trials Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomised, double blind, parallel group, placebo controlled, Phase 3 trial of Exenatide once weekly over 2 years as a potential disease modifying treatment for Parkinson's disease.

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 18, 2020
• Study Start: January 20, 2020
• Primary Completion: February 24, 2024
• Study Completion: July 31, 2024
• Last Updated: May 6, 2026

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)