Safety Evaluation Study of Pitavastatin PLGA Nano-particle for Retinitis Pigmentosa

Investigator-initiated Phase 1 Clinical Trial to Evaluate the Safety of Pitavastatin PLGA Nano-particle in Patients With Retinitis Pigmentosa

Retinitis pigmentosa (RP) is a rare inherited retinal degenerative disease that causes progressive visual field loss and vision impairment, often leading to blindness. Currently, there are limited treatment options capable of slowing disease progression for the majority of patients with RP. Preclinical studies have suggested that retinal inflammation, particularly the activity of inflammatory monocytes and macrophages, may contribute to photoreceptor degeneration. ULREA-PVS-NP is a novel intravenous formulation consisting of pitavastatin encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, developed to target inflammatory pathways associated with retinal degeneration. Preclinical studies demonstrated suppression of inflammatory monocyte/macrophage activity and preservation of photoreceptors in animal models of RP.

This is a single-center, open-label, investigator-initiated Phase 1 study designed to evaluate the safety of intravenous ULREA-PVS-NP in adults with RP. The study consists of two parts. In Part 1, participants will receive a single intravenous infusion of ULREA-PVS-NP at escalating dose levels (2 mg, 4 mg, or 8 mg) to evaluate safety and tolerability. Following review of safety data, Part 2 will evaluate repeated administration of the highest dose considered safe in Part 1, given once every four weeks for a total of three administrations.

The primary objective is to evaluate the safety of ULREA-PVS-NP by assessing the incidence of adverse events. Secondary objectives include characterization of pharmacokinetic profiles, evaluation of changes in clinical laboratory tests and vital signs, and exploratory assessment of ophthalmologic outcomes and inflammatory biomarkers.

Inclusion Criteria:

1. Patients diagnosed with typical retinitis pigmentosa by two ophthalmologists according to the Clinical Practice Guidelines for Retinitis Pigmentosa (genomic diagnosis will not be performed).

2. Patients aged 18 years or older and 70 years or younger at the time of informed consent.

3. * Patients with a mean retinal sensitivity of 10 dB or higher within the central 4 degrees (12 points) of the Humphrey 10-2 visual field.

4. * Patients whose difference in mean retinal sensitivity (MD value) between two Humphrey 10-2 examinations at screening is within 3 dB. If the criteria are not met in the second examination, a third measurement will be performed within 14 days of the second examination, and the difference between the third measurement and the first or second measurement must be within 3 dB.

5. * Patients with a foveal retinal thickness of 250 micrometer or less as measured by optical coherence tomography.

   *At least one eye must meet criteria 3, 4, and 5.

6. Female patients of childbearing potential who agree to use appropriate contraception from the time of informed consent until 180 days after the last dose of the investigational product.

7. Male patients who agree to use appropriate contraception for 3 days from each administration of the investigational product.

8. Patients who can provide written informed consent.

Exclusion Criteria:

1. Patients currently taking statins for hyperlipidemia.
2. Patients who have received helenien, unoprostone, or calcium channel blockers for the treatment of eye diseases within 30 days prior to informed consent.
3. Patients scheduled for ophthalmic surgery during the study period.
4. Patients with concomitant glaucoma or ocular hypertension.
5. Patients with concomitant uveitis or optic neuritis.
6. Patients with retinal lesions not attributable to retinitis pigmentosa (e.g., fundus hemorrhage, retinal edema, proliferative tissue, etc.) observed on fundus examination.
7. Patients with a history of hypersensitivity or severe adverse reactions to pitavastatin calcium or any component of the investigational product.
8. Patients with severe allergies or a history thereof.
9. Patients with severe renal impairment.
10. Patients with severe cardiac dysfunction or heart failure.
11. Patients with severe hepatic impairment.
12. Patients with biliary obstruction.
13. Patients with active inflammatory diseases or infections (e.g., active collagen disease, rheumatoid arthritis, ulcerative colitis, sepsis, etc.).
14. Patients with a history of cerebral hemorrhage, cerebral infarction, or ischemic heart disease within 6 months prior to informed consent.
15. Patients with hematological disorders (e.g., severe anemia, leukemia, aplastic anemia, etc.).
16. Patients with alcohol dependence, drug dependence, or mental disorders that may interfere with study participation.
17. Patients with concomitant malignant tumors or who have received treatment for malignant tumors within the past 3 years.
18. Patients currently receiving cyclosporine.
19. Patients currently receiving fibrate drugs (e.g., clofibrate, fenofibrate, bezafibrate, etc.) who cannot discontinue fibrate drugs from 3 days prior to the start of investigational product administration.
20. Patients currently receiving nicotinic acid, erythromycin, or rifampicin who cannot discontinue these drugs from 3 days prior to the start of investigational product administration.
21. Patients currently participating in other clinical trials or studies.
22. Pregnant women, women suspected of being pregnant, or lactating women.
23. Any other patient judged unsuitable by the principal investigator or sub-investigator.