Safety and Efficacy of Stem Cell Small Extracellular Vesicles in Patients With Retinitis Pigmentosa

Retinitis Pigmentosa Clinical Trial

Official title:

Safety and Efficacy Evaluation of Intravitreal Injection of GMP-compliant Bone Marrow Mesenchymal Stem Cell-derived Small Extracellular Vesicles in Patients With Retinitis Pigmentosa

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06242379
• Other study ID #: R016534006
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: September 1, 2024
• Est. completion date: February 2026

Study information

• Verified date: March 2024
• Source: Mahidol University
• Contact: Laongsri Atchaneeyasakul, Professor
• Phone: +66 893138367
• Email: atchanee[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this clinical trials is to evaluate the safety and efficacy of intravitreal injection of GMP-compliant BM-MSC-derived sEVs in patients with retinitis pigmentosa.

Description:

Inherited retinal disease (IRD) is one of the leading causes of blindness in adolescents and adults, affecting 1 in 2,000 to 3,000 people globally. Recently, advances arose in the use of stem cells as treatment modalities for inherited retinal diseases, including retinitis pigmentosa (RP). The first step, production and characterization of GMP-compliant bone marrow mesenchymal stem cell (BM-MSC)-derived small extracellular vesicles (sEVs) has been performed according to the ethical clearance by the institutional review board of the Faculty of Medicine Siriraj Hospital Mahidol University (approval number Certificate of Approval (COA) no. Si 57112022, protocol number 44312565 (1RB1), dated August 8, 2022). In a prior study, the investigators have conducted a phase I clinical trial to assess the safety of intravitreal autologous MSC injection in 14 patients with advanced-stage RP. After follow-up periods ranging from 1.5 to 7 years, the investigators found that this intervention appeared to be safe and potentially effective. Nevertheless, several mild and one severe adverse event were observed, although all were manageable. Beside the primary outcome, safety of the MSCs, the investigators found statistically significant improvements in the best corrected visual acuity (BCVA) compared to baseline, although they returned to the baseline at 12 months. To minimize the unwanted effects and still maintain the benefit of the MSCs, the cell-free approach using the extracellular vesicles of MSCs is of interest. On the current study, the investigators would like to evaluate the safety and efficacy of intravitreal injection of GMP-compliant BM-MSC-derived sEVs in patients with retinitis pigmentosa.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: February 2026
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years or above
• Clinically diagnosed with RP by experienced ophthalmologists or having documented mutations in the genes responsible for RP
• Central visual field in the better eye less than or equal to 20 degrees
• Best corrected visual acuity (BCVA) in the worse eye 6/18 (logMAR 0.48) to 6/120 (logMAR 1.3) by Snellen visual acuity chart
• Electroretinogram in the worse eye nonrecordable or the amplitudes were less than 25% of normal
• Willing and able to give informed consent for participation in the study

Exclusion Criteria:

• Intolerance and/or contraindication to local anesthesia and other substances used during the procedure
• Pregnant or lactating woman
• Having blood-borne infections, i.e. Human immunodeficiency virus (HIV), hepatitis B or C, Human T-lymphotropic viruses (HTLV)
• Having any other significant ocular or non-ocular disease/disorder which may either put the subjects at risk because of participation in the study, or may influence the results of the study, or the subjects ability to participate in the study. This includes

1. Inherited or acquired bleeding disorders, including the use of anticoagulant medications that cannot be stopped prior the procedure

2. Autoimmune diseases, i.e., systemic lupus erythematosus, multiple sclerosis, fibromyalgia, Guillain-Barre syndrome

3. Severe/uncontrolled chronic/metabolic diseases, e.g., diabetes mellitus, cardiovascular disease, chronic kidney disease, transient ischemic attack (TIA)/stroke

• Unable to complete the full course of the study or failed to return for follow up

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa

Intervention

Biological:
• GMP compliant-BM-MSC derived sEVs
The procedure will be performed under topical anesthesia (0.5% tetracaine hydrochloride ophthalmic solution). The intravitreal injection will be performed by the retina specialist. Topical antiseptic (5% povidone iodine solution) will be applied on the periorbital and ocular surface. Eyelid speculum will be inserted to expose the injection area. It will include an intravitreal injection at the superotemporal quadrant (right eye) and superonasal quadrant (left eye), 3.5 to 4 mm posterior to the limbus. A 30-gauge needle will be used to deliver a 0.05 to 0.1 ml sEV suspension into the vitreous cavity. Indirect ophthalmoscopy will be performed immediately after the procedure to ensure no occlusion of the central retinal artery. The eye will be rinsed thoroughly by normal saline to wash out remaining antiseptic. The total duration for an intravitreal injection will be approximately 30 minutes.

Locations

Country	Name	City	State
Thailand	Siriraj Hospital	Bangkok Noi	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (22)

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Tuekprakhon A, Sangkitporn S, Trinavarat A, Pawestri AR, Vamvanij V, Ruangchainikom M, Luksanapruksa P, Pongpaksupasin P, Khorchai A, Dambua A, Boonchu P, Yodtup C, Uiprasertkul M, Sangkitporn S, Atchaneeyasakul LO. Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa. Stem Cell Res Ther. 2021 Jan 9;12(1):52. doi: 10.1186/s13287-020-02122-7. — View Citation

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* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events	To evaluate the safety of the intervention. The evaluations include the intraocular pressure in mmHg, cell value in number of cells in 0.5 cubic millimeter and flare value in photons per millisecond, anterior segment examination using slit lamp biomicroscopy, fundus evaluation using fundus photography, retinal assessment, and subjective complaints of study participants.	1 year
Primary	Ophthalmological parameters	To observe the efficacy of the intervention. The evaluations comprise the best corrected visual acuity (BCVA) in the Logarithm of the Minimum Angle of Resolution (LogMAR) score. The value "0" indicates "no loss", that is visual acuity equal to the reference standard (1.0, 20/20). Visual acuity better tans 1.0 (20/20) is represented by negative LogMAR values. LogMAR 1.0 is equivalent to 20/200. Blindness is defined as a best-corrected visual acuity worse than 1.3 LogMAR.	1 year
Primary	Ophthalmological parameters	contrast sensitivity test using the Stereo Optical Functional Vision Analyzer (FVA) to measure contrast sensitivity by generating a contrast sensitivity function curve that portrays sensitivity on the Y-axis and spatial frequency on the X-axis.	1 year
Primary	Ophthalmological parameters	sweep visual evoked potential in Snellen unit	1 year
Primary	Ophthalmological parameters	kinetic visual field test in degree field of vision at four quadrants (superior, nasal, inferior, temporal)	1 year
Primary	Ophthalmological parameters	optic disc and cup volume in cubic millimeter	1 year
Primary	Ophthalmological parameters	retinal nerve fiber layer thickness in micron	1 year
Primary	Ophthalmological parameters	electrophysiology (electroretinography in microvolt, visual evoked potential in millisecond and microvolt, multifocal electroretinography in signal strength response)	1 year
Primary	Ophthalmological parameters	optical coherence tomography of the macula in micron	1 year
Primary	Ophthalmological parameters	optical coherence tomography angiography in percent of vessel flow density	1 year
Primary	Ophthalmological parameters	foveal avascular zone in square millimeter	1 year
Primary	Ophthalmological parameters	macular thickness in micron	1 year