Clinical trial NCT04269642: SR-Exenatide (PT320) to Eveluate Efficacy and Safety in Patients With Early Parkinson's Disease
Official title: Phase IIa Study to Evaluate the Efficacy and Safety of Subcutaneous SR-Exenatide (PT320) in Patients With Early Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Early Parkinson's Disease
Lead sponsor: Peptron, Inc.
Sponsor class: INDUSTRY
First posted: 2020-02-17
Enrollment: 99
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to evaluate the safety and efficacy of sustained release (SR)-Exenatide (PT320, Q1W and Q2W) in the treatment of patients with early Parkinson's disease (PD).

Detailed description: This study is a multicenter, randomized, double-blind, placebo-controlled, parallel comparison, phase IIa clinical study to evaluate the efficacy and safety of sustained release (SR)-Exenatide (PT320) in the treatment of patients with early Parkinson's disease (PD).

Exenatide (GLP-1) has been approved by the Food and Drug Administration (FDA) to treat patients with Type 2 Diabetes (T2D) and obesity. In addition, several research groups have confirmed that Exenatide has beneficial aspects due to the neuroprotective effects in neuronal cells in patients with PD. Peptron has developed a sustained-release (SR)-Exenatide, (PT320, Q1W and Q2W), which has shown a higher Blood-Brain Barrier (BBB) penetration rate and better patient compliance.

Thus, the objective of this study is to evaluate the effect of PT320 on symptom improvement and the inhibition of disease progression in the treatment of patients with early Parkinson's disease. Also, pharmacokinetic analysis of PT320 in blood cerebrospinal fluid (CSF) and exosome analysis of biomarkers related to Exenatide will be being tested, as exploratory measurements.

Eligibility criteria: Inclusion Criteria:

1. Patient who is male or female aged 40-75 and is diagnosed with Parkinson's Disease (using Queen Square Brain Bank criteria)
2. Patient who is diagnosed of Parkinson's Disease less than 24 months prior to the screening
3. Patient who has a modified Hoehn and Yahr stage ≤ 2. 5
4. Patient who has been taking L-dopa stable-dose less than 600 mg/day or who has not previously taken any medication for the treatment of Parkinson's Disease from 4 weeks prior to the screening.
5. Patient who is able to inject an Investigational Product by himself/herself or a his/her guardian.
6. Patient or legally acceptable representative who signs the informed consent form voluntarily and is able to comply with all study procedures

Exclusion Criteria:

1. Patient who is diagnosed or suspected to have Parkinson-plus syndromes (e.g., Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Degeneration, Diffuse Lewy Body Disease, and etc.)
2. Patient who has a BMI \< 18.5 at the screening
3. Patient who has known abnormalities on CT or MRI brain imaging that may have an impact on the protocol compliance and/or PET scan
4. Patient who has dementia with MoCA-K ≤ 22
5. Patient who has a history of severe heart failure (NYHA class III to IV), stroke, cerebral ischemic attack, or seizure within 1 year prior to screening; or a history myocardial infarction or unstable angina within 6 months prior to screening.
6. Patient who has severe liver disease or has AST or ALT level 3 times more than ULN at the screening
7. Patient who has clinically significant depression \[\> 18 of Korean Beck Depression Inventory II score (K-BDI-II)\]
8. Patient who has a history of brain surgery for any treatment of Parkinson's disease
9. Patient who has participated in any clinical trials for the treatment of Parkinson's Disease within 3 months prior to screening
10. Patient who took exenatide within 90 days prior to randomization
11. Patient who has a history of gastroduodenal ulcer or gastroparesis within 3 months prior to administration of investigational product or is currently on medication for acute or chronic gastritis
12. Patient who has severe kidney function injury (creatinine clearance \< 30 ml/min)
13. Patient who has a history of pancreatitis
14. Patient who has type 1 or type 2 diabetes or HbA1c ≥ 6.5% at screening
15. Patient who has a history or suspected to thyroid cancer or multiple endocrine adenomatosis
16. Patient who has known or suspected intolerance in PET scan or fluoropropyl-CIT (18F)
17. Woman childbearing potential who doesn't agree to use the medically acceptable methods of contraception\* during this study and up to 24 weeks after the last injection of investigational product

    \*Medically acceptable methods of contraception: oral contraceptives, intrauterine contraceptive devices, vasectomy for male partner, barrier method \[condom, spermicidal foam/gel/film/cream/suppository with sealed cap (diaphragm or cervix/bolt cap)\].
18. Woman who is pregnant or breastfeeding
19. Patient who has a history of hypersensitivity reactions to any ingredients of investigational product
20. Patient who is not eligible for the study at the discretion of the investigator

Primary outcomes:
measure: Change of MDS-UPDRS part 3 score
timeFrame: 48 week
Secondary outcomes:
measure: SNBR (specific to non-specific binding ratio) confirmed by PET scan
timeFrame: 0 and 48 weeks
measure: MDS-UPDRS part 3 score
timeFrame: 0, 24 and 60 weeks
measure: MDS-UPDRS part 1, 2 and 4 scores
timeFrame: 0, 24, 48 and 60 weeks
measure: K-PDQ-39 score
timeFrame: 0, 48 and 60 weeks
measure: MoCA-K score
timeFrame: 0, 24, 48 and 60 weeks
measure: K-NMSS score
timeFrame: 0, 24, 48 and 60 weeks
measure: Each percentage of subjects and changing patterns in modified Hoehn and Yahr stage
timeFrame: 0, 24, 48 and 60 weeks
measure: Change of the L-dopa dosage of subjects
timeFrame: 0, 2, 4, 8, 12, 24, 36, 48 and 60 weeks
Other outcomes:
measure: Pharmacokinetics test with blood
timeFrame: 0, 12, 24, 36, 48 and 60 weeks
measure: Pharmacokinetics test with CSF
timeFrame: 0, 12, 24, 36, 48 and 60 weeks
measure: Anti-exenatide antibodies test in blood
timeFrame: 0, 12, 24, 36, 48 and 60 weeks
Locations:
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul Metropolitan Government Seoul National University Boramae Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Peptron, Inc.
name: Min Ho Ihm
role: STUDY_DIRECTOR
References: