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

May 12, 2025 updated by: Mahidol University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Thailand
    • Bangkok
      • Bangkok Noi, Bangkok, Thailand, 10700
        • Recruiting
        • Siriraj Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bone marrow-mesenchymal stem cell-derived small extracellular vesicles
Single intravitreal injection of Good Manufacturing Practice (GMP) compliant bone marrow (BM)-mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) (50 μg) for single eye
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ophthalmological parameters
Time Frame: 1 year
sweep visual evoked potential in Snellen unit
1 year
Ophthalmological parameters
Time Frame: 1 year
optic disc and cup volume in cubic millimeter
1 year
Ophthalmological parameters
Time Frame: 1 year
retinal nerve fiber layer thickness in micron
1 year
Ophthalmological parameters
Time Frame: 1 year
electrophysiology (electroretinography in microvolt, visual evoked potential in millisecond and microvolt, multifocal electroretinography in signal strength response)
1 year
Ophthalmological parameters
Time Frame: 1 year
optical coherence tomography of the macula in micron
1 year
Incidence of treatment-emergent adverse events
Time Frame: 1 year
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
Ophthalmological parameters
Time Frame: 1 year
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
Ophthalmological parameters
Time Frame: 1 year
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
Ophthalmological parameters
Time Frame: 1 year
kinetic visual field test in degree field of vision at four quadrants (superior, nasal, inferior, temporal)
1 year
Ophthalmological parameters
Time Frame: 1 year
optical coherence tomography angiography in percent of vessel flow density
1 year
Ophthalmological parameters
Time Frame: 1 year
foveal avascular zone in square millimeter
1 year
Ophthalmological parameters
Time Frame: 1 year
macular thickness in micron
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mahidol University

Investigators

  • Principal Investigator: Laongsri Atchaneeyasakul, Professor, Mahidol University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 23, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

January 12, 2024

First Submitted That Met QC Criteria

February 2, 2024

First Posted (Actual)

February 5, 2024

Study Record Updates

Last Update Posted (Actual)

May 15, 2025

Last Update Submitted That Met QC Criteria

May 12, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R016534006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Need a consensus from colleagues; Personal reasons

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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