Clinical trial NCT06242379: Safety and Efficacy of Stem Cell Small Extracellular Vesicles in Patients With Retinitis Pigmentosa
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Retinitis Pigmentosa
Keywords: Retinitis pigmentosa
small extracellular vesicles
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2024-02-05
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
measure: Ophthalmological parameters
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Bangkok Noi
country: Thailand
facility: Siriraj Hospital
state: Bangkok
Study officials:
affiliation: Mahidol University
name: Laongsri Atchaneeyasakul, Professor
role: PRINCIPAL_INVESTIGATOR
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