Effect of Exenatide on disease progression in early Parkinson’s disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Stockholm – SLSO

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

21 Jan 2020 → ongoing

Decision date (initial)

2024-12-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520069-30-00

EudraCT number

2019-000732-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic

To identify the biological mechanisms that mediate Exenatide-effect in the brain, and to measure true treatment-effect of Exenatide that is independent of the concurrent, symptomatic, dopaminergic treatment.
To evaluate the effect on motor-symptom progression. (open-label extension part one).
To evaluate the rate and severity of AEs and the number of AEs related to long-term exposure to Exenatide(open-label extension part two).

Secondary objectives 7

1. To compare the effect of Exenatide to placebo on disease progression.
2. To compare the effect of Exenatide to placebo on motor-symptom progression.
3. To compare the effect of Exenatide to placebo on the non-motor symptom progression.
4. To measure the safety of Exenatide in patients with PD.
5. To evaluate pharmacokinetic properties of Exenatide.
6. Frequency of adverse events (open-label extension part one).
7. To evaluate changes in motor, and non-motor symptoms activities of daily living and complications by dopaminergic treatment (open-label extension part one and two ).

Conditions and MedDRA coding

Parkinson's disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Diagnosis of clinically probable Parkinson’s disease according to the MDS clinical diagnostic criteria for PD
2. Males or Females
3. Hoehn and Yahr stage ≤ 2 in the ON medication state. This implies that all patients will be mobile without assistance during their best “ON” medication periods
4. Patients are on levodopa treatment.
5. No need for extended treatment adjustment, no significant motor fluctuations during the last year.
6. All patients will be ≥25 and ≤80 years of age.
7. Ability to self-administer, or to arrange carer administration of the trial drug.
8. Signed informed consent to participate in the trial.
9. Successful completion of the blinded part of the trial “Effect of Exenatide on disease progression in early Parkinson’s disease” (open-label extension part one)
10. In the opinion of the investigator PD-diagnosis is still valid and the subject remains eligible for treatment. (open-label extension part one and two)
11. Successful completion of the blinded part of the trial “Effect of Exenatide on disease progression in early Parkinson’s disease” and the first extension, open-label trial.(open-label extension part two)

Exclusion criteria 29

1. Atypical or other causes of parkinsonism. Patients with suspected Multiple System Atrophy, Progressive Supranuclear Palsy, drug-induced parkinsonism, vascular parkinsonism, dystonic or essential tremor will not be included in the trial.
2. Prior intra-cerebral surgical intervention for Parkinson’s disease. Patients who have previously undergone Deep Brain Stimulation, intra-cerebral administration of growth factors, gene therapy or cell therapies will not be eligible.
3. Already actively participating in a trial of a device, drug or surgical treatment for Parkinson’s disease.
4. Previous exposure to Exenatide.
5. Known abnormality on CT or MRI brain imaging considered likely to compromise compliance with trial protocol/FDG-PET acquisition.
6. Patients with body mass index < 18.5. Exenatide causes weight loss, and individuals with already low BMI will not be eligible.
7. Patients with diabetes mellitus type 1.
8. Patients with prediabetes (HbA1c at screening 42-47 mmol/mol), or T2DM (known diagnosis, ongoing antidiabetic treatment or HbA1c > 47 mmol-mol and fasting plasma glucose > 7.0 mmol/L at screening).
9. History of pancreatitis. Baseline serum amylase value should be within the laboratory normal range +/- 20%.
10. Severe gastrointestinal disease including gastroparesis.
11. History of alcoholism.
12. History of severe cardiac disease.
13. History of pancreas cancer.
14. History or suspicion of thyroid cancer. Undiagnosed neck lump, hoarse voice, or difficulty swallowing not attributable to PD.
15. Personal or family history of medullary thyroid cancer.
16. Patients with Multiple Endocrine Neoplasia 2 (MEN2) syndrome.
17. End stage renal disease or creatinine clearance < 50 ml/min.
18. Hyperlipidaemia. A lipid profile will be tested at the screening visit. Cholesterol or Triglyceride levels greater than 2 x the upper limit of normal will raise suspicion of a familial or acquired hyperlipidaemia and will prompt referral to a relevant specialist for investigation and treatment.
19. Concurrent treatment with warfarin.
20. Concurrent severe depression, defined as MADRS score > 16.
21. Concurrent dementia, defined as MMSE < 22.
22. Pregnancy and Breastfeeding.
23. There are no safety data regarding Exenatide use in pregnancy. Women of childbearing potential should only be included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test, and will be asked at each visit to confirm regular use of an effective method of contraception. Those who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and until the end of the relevant systemic exposure period (i.e. 10 weeks after the last dose of study drug) will not be eligible. The following birth control methods are considered to be acceptable: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, and sexual abstinence.
24. Known hypersensitivity or allergy or intolerance to GLP-1.
25. Known hypersensitivity to Exenatide or any of its excipients.
26. Potential participants who lack the capacity to give informed consent
27. Any medical, psychiatric or other condition which in the investigator’s opinion compromises the potential participant's ability to participate in the trial.
28. Treatment with investigational medication other than Exenatide within 4 weeks prior to the enrolment in the open-label part of the study.(open-label extension part one and two)
29. Revision of the initial PD diagnosis. Suspicion of Atypical or other causes of parkinsonism such as suspected Multiple System Atrophy, Progressive Supranuclear Palsy, drug-induced parkinsonism, vascular parkinsonism, dystonic or essential tremor.(open-label extension part one and two)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. FDG-PET network analysis at baseline, 9 and 21 months

Secondary endpoints 6

1. MDS-UPDRS part 3 in OFF-medication state and accelerometer-based parameters of physical activity, MDS-UPDRS part 3 in ON-medication state, MDS-UPDRS parts 1, 2 and 4, biofluid-based parameters at baseline, 9, 18 and 21 months
2. LEDD at baseline, 3, 6, 9, 12, 15, 18 and 21 months
3. PDQ-39, NMSQuest, ESS at baseline, 6, 12, 18 months
4. MoCA at baseline, 9 and 21 months
5. B-SIT at baseline, 9 and 18 months
6. MADRS at screening, 6, 12 and 18 months

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Stockholm – SLSO

Sponsor organisation

Region Stockholm – SLSO

Address

Solnavagen 1 E, S:t Matteus S:t Matteus

City

Stockholm

Postcode

113 65

Country

Sweden

Scientific contact point

Organisation

Region Stockholm – SLSO

Contact name

Principal Investigator

Public contact point

Organisation

Region Stockholm – SLSO

Contact name

Principal Investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications