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Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease

Early Phase 1
Completed
Conditions
Cornea
Mesenchymal Stromal Cells
Corneal Defect
Corneal Epithelium Defect
Interventions
Biological: MSC Secretome Eye Drops
Registration Number
NCT05204329
Lead Sponsor
University of Illinois at Chicago
Brief Summary

This study is a longitudinal assessment using a classic dose-escalation study design to assess the safety and maximal tolerated dose (MTD) of topical MSC Secretome eye drops. The study will be conducted at Illinois Eye and Ear Infirmary located at University of Illinois at Chicago. The study will use anterior segment Optical Coherence Tomography (OCT)/Scheimpflug Imaging, esthesiometry, and visual analogue scale (VAS) to assess treatment tolerability.

Detailed Description

The "Safety of Topical Mesenchymal Stromal Cell Secretome for Ocular Surface Disease" study is designed to evaluate the safety and maximal tolerated dose (MTD) of topical MSC Secretome eye drops in patients with chronic ocular surface disease through a dose-escalation study under a 28-day topical application protocol, and also obtain a preliminary observation on the following:

1. Incidence of treatment emergent adverse events (TEAE) assessed at 28 days following treatment initiation

2. Proportion of patients with improved corneal epithelial barrier at 28 days compared to baseline

3. Final visual acuity, corneal epithelial thickness, corneal stromal haze, corneal sensation, and treatment tolerability

The objective is to determine the dose of MSC Secretome through a first-in-human study through a dose-escalation strategy targeting a toxicity rate of 33% or less.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9
Inclusion Criteria
  • Patients 18 years of age or older
  • Chronic corneal epithelial disease with fluorescein staining score ≥ 6 by NEI grading scale
  • Reduced corneal sensation (≤ 4 cm measured by Cochet Bonnet esthesiometry) in at least one corneal quadrant
  • A stable ocular surface with no objective clinical evidence of significant (> 50%) improvement/worsening of the epithelial disease in the last 30 days
  • Epithelial disease refractory to conventional non-surgical treatments (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops; anti-inflammatory therapy)
Exclusion Criteria
  • Any active or suspected ocular infection (bacterial, viral, fungal or protozoal).
  • Evidence of corneal ulceration with stromal loss > 10%
  • Presence of an epithelial defect ≥1.0 mm in the largest diameter in the affected eye
  • Presence of any size epithelial defect that has been persistent for more than 30 days
  • Patients unable to discontinue or intermittently remove therapeutic contact lens in the study eye (to apply drops) during the 4-week study period
  • History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye within the 3 months prior to study enrollment
  • History of chemical injury within the last 6 months prior to study enrollment Known hypersensitivity to one of the components of the study or procedural medications (e.g.,fluorescein)
  • History of drug, medication or alcohol abuse or addiction
  • Use of any investigational agent within 4 weeks of screening visit
  • History of previous enrollment in the MSC Secretome Study at a lower dose
  • Participation in another clinical study at the same time as the present study
  • Participants who are pregnant at the time of study enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Low dose of allogenic MSC dropsMSC Secretome Eye DropsEscalating doses of allogenic MSC eye drops will be assigned at the lowest dose level.
Medium dose of allogenic MSC dropsMSC Secretome Eye DropsEscalating doses of allogenic MSC eye drops will be assigned at the medium dose level.
High dose of allogenic MSC dropsMSC Secretome Eye DropsEscalating doses of allogenic MSC eye drops will be assigned at the high dose level.
Primary Outcome Measures
NameTimeMethod
Epithelial Status AssessmentDay 28

The primary outcome measure is improved corneal epithelial barrier function at DAY #28assessed by viewing the cornea under slit lamp examination after instillation of sodium fluorescein, assessing the change from baseline in corneal fluorescein staining score. The presence/absence of an epithelial defect on DAY #28 will also be recorded.

Secondary Outcome Measures
NameTimeMethod
Durability of Corneal Epithelial Status ImprovementBaseline, Days 7, 14, 28, 56, 90

Durability of the improved corneal epithelial barrier function/integrity will be assessed an outcome measure at DAY #56 and DAY #90. Participants with improved corneal epithelial barrier function/integrity to DAY #28 will be assessed at each subsequent follow-up visits (e.g., DAYS #56, #90) to assess persistence of the healing response.

Corneal Epithelial thicknessBaseline, Days 14, 28, 56, 90

Corneal epithelial thickness measured by anterior segment OCT imaging (Cirrus 6000, Pachymetry, a-scans and b-scans) will assess the treatment effect on thickness on DAY #28 and compared relative to baseline.

Visual AcuityBaseline, Days 7, 14, 28, 56, 90

Best-corrected distance visual acuity will be measured using standard ETDRS protocols.

Tolerability of MSC secretome dropsBaseline, Days 7, 14, 28, 56, 90

Drop discomfort will be measured at DAYS #7, #14, and #28 using a visual analogue scale (VAS; range 0 -100), where 0 represents no discomfort and 100 the worst discomfort.

Corneal Scarring / HazeBaseline, Days 14, 28, 56, 90

Corneal scarring/haze will be assessed via anterior segment OCT imaging (Cirrus 6000; HD cornea, a-scans) to assess the treatment effect on DAY #28 relative to baseline(Images analysis done by Image-J/Metamorph)

Time to Improvement of Corneal Epithelial BarrierBaseline, Days 7, 14, 28, 56, 90

The time required for an improved epithelial barrier function will be assessed at each visit throughout the trial.

Trial Locations

Locations (1)

University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

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