oGVHD, Ocular Graft Versus Host Disease
Conditions
Keywords
oGVHD, Ocular Graft-Versus-Host Disease, Ocular Graft Versus Host Disease
Brief summary
This is a Phase III, multicenter, randomized, double-masked, vehicle-controlled, parallel-group clinical trial designed to evaluate the efficacy, safety, and tolerability of d-MAPPS™ Ophthalmic Solution in adult subjects with chronic ocular graft-versus-host disease (oGVHD). Eligible subjects will receive masked study treatment for 90 days, with the primary efficacy assessment performed at the Day 90 study visit.
Interventions
BIOLOGICALd-MAPPS™ Ophthalmic Solution
Sterile, preservative-free ophthalmic solution administered as two drops into each eye four times daily for 90 consecutive days.
BIOLOGICALMatching vehicle control
Matching vehicle control supplied in identical masked containers and administered as two drops into each eye four times daily for 90 consecutive days.
Sponsors
Regenerative Ocular Immunobiologics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older. * Documented chronic ocular graft-versus-host disease (oGVHD) following allogeneic hematopoietic stem cell transplantation. * Investigator determines the participant is medically stable and appropriate for study participation. * Ocular Surface Disease Index (OSDI) Total Score of at least 33 at Baseline. * UNC Dry Eye Management Scale Visual Analog Scale (UNC DEMS VAS) score of at least 3 at Baseline. * Modified Oxford Corneal Staining Score of at least 1 in at least one eye. * Snellen Corrected Distance Visual Acuity sufficient to complete protocol-defined assessments. * Written informed consent obtained before study procedures. * Willing and able to comply with study visits, study treatment, and protocol requirements. * Background therapies stable for at least 30 days before Baseline.
Exclusion criteria
* Acute ocular graft-versus-host disease or ocular disease that may interfere with efficacy assessment. * Active ocular or periocular infection, ocular malignancy, or active herpetic keratitis. * Intraocular surgery, refractive surgery, or ocular laser procedure within 6 weeks before Baseline or planned during the study. * Change in systemic immunosuppressive therapy, topical glaucoma therapy, or oral tetracycline therapy within 30 days before Baseline. * Initiation within 30 days before Baseline or during the trial of topical cyclosporine, lifitegrast, tacrolimus, autologous serum eye drops, platelet-rich plasma eye drops, amniotic membrane products, or another prescription therapy intended to treat ocular surface disease. * Participation in another investigational study within 30 days before Screening or concurrent enrollment. * Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 90 in Ocular Surface Disease Index (OSDI) Total Score | Baseline to Day 90 (±5 days) | The Ocular Surface Disease Index (OSDI) will assess ocular symptoms and their effect on vision-related functioning. Total scores range from 0 to 100, with higher scores representing greater symptom burden. A decrease from Baseline indicates improvement. |
| Change From Baseline to Day 90 in Modified Oxford Corneal Staining Score | Baseline to Day 90 (±5 days) | Corneal fluorescein staining will be assessed in the prespecified study eye using the Modified Oxford grading scale. Scores range from 0 to 5, where 0 represents no corneal staining and higher scores represent progressively greater staining. A decrease from Baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a ≥1-Grade Decrease in Modified Oxford Corneal Staining Score | Baseline to Day 90 (±5 days) | The proportion of participants achieving at least a 1-grade decrease from Baseline to Day 90 in the prespecified study eye. Scores range from 0 to 5, with higher scores indicating greater corneal staining. A decrease indicates improvement. |
| Change From Baseline to Day 90 in Supportive Efficacy Measures in the Fellow Eye | Baseline to Day 90 (±5 days) | Supportive analyses will evaluate change from Baseline to Day 90 separately for protocol-defined measures collected in the fellow eye, including the Modified Oxford Corneal Staining score, superficial punctate keratitis (SPK) severity, and tear break-up time (TBUT). Modified Oxford scores range from 0 to 5, with higher scores indicating greater corneal staining; a decrease indicates improvement. Lower SPK severity indicates improvement. TBUT is measured in seconds; an increase indicates improved tear-film stability. No composite score will be calculated. |
| Percentage of Participants With Modified Oxford Corneal Staining Score Grade 0 at Day 90 | Day 90 (±5 days) | The proportion of participants with a Modified Oxford Corneal Staining Score of Grade 0 in the prespecified study eye at Day 90. Scores range from 0 to 5, with higher scores indicating greater corneal staining and a worse outcome. Grade 0 indicates no corneal staining. |
| Change From Baseline to Day 90 in Superficial Punctate Keratitis (SPK) Severity | Baseline to Day 90 (±5 days) | Change from Baseline to Day 90 in the protocol-defined Superficial Punctate Keratitis (SPK) Severity Grade in the prespecified study eye. Grades range from 0 (no SPK) to 4 (severe SPK), with higher grades indicating greater severity and a worse outcome. A decrease indicates improvement. |
| Percentage of Participants With a ≥1-Grade Decrease in Superficial Punctate Keratitis (SPK) Severity | Baseline to Day 90 (±5 days) | The proportion of participants achieving at least a 1-grade decrease from Baseline to Day 90 in the protocol-defined Superficial Punctate Keratitis (SPK) Severity Grade in the prespecified study eye. Grades range from 0 (no SPK) to 4 (severe SPK), with higher grades indicating greater severity and a worse outcome. A decrease indicates improvement. |
| Percentage of Participants With Superficial Punctate Keratitis (SPK) Severity of 0 at Day 90 | Day 90 (±5 days) | The proportion of participants with a Superficial Punctate Keratitis (SPK) Severity Grade of 0 in the prespecified study eye at Day 90. Grades range from 0 (no SPK) to 4 (severe SPK), with higher grades indicating greater severity and a worse outcome. Grade 0 indicates complete resolution of SPK. |
| Percentage of Participants With a ≥13-Point Decrease in OSDI Total Score | Baseline to Day 90 (±5 days) | The proportion of participants achieving a decrease of at least 13 points from Baseline to Day 90 in Ocular Surface Disease Index (OSDI) Total Score. Scores range from 0 to 100, with higher scores indicating greater symptom burden. A decrease indicates improvement. |
| Change From Baseline to Day 90 in NIH Eye Score | Baseline to Day 90 (±5 days) | Change from Baseline to Day 90 in the National Institutes of Health (NIH) Eye Score. Scores range from 0 (no ocular symptoms) to 3 (severe ocular involvement), with higher scores indicating greater ocular graft-versus-host disease severity and a worse outcome. A decrease indicates improvement. |
| Percentage of Participants With a ≥1-Grade Decrease in NIH Eye Score | Baseline to Day 90 (±5 days) | The proportion of participants achieving at least a 1-grade decrease from Baseline to Day 90 in the National Institutes of Health (NIH) Eye Score. Scores range from 0 (no ocular symptoms) to 3 (severe ocular involvement), with higher scores indicating greater ocular graft-versus-host disease severity and a worse outcome. A decrease indicates improvement. |
| Percentage of Participants With No Worsening in NIH Eye Score at Day 90 | Baseline to Day 90 (±5 days) | The proportion of participants whose National Institutes of Health (NIH) Eye Score at Day 90 is equal to or lower than their Baseline score. Scores range from 0 (no ocular symptoms) to 3 (severe ocular involvement), with higher scores indicating greater ocular graft-versus-host disease severity and a worse outcome. A lower score indicates improvement, while an unchanged score indicates no worsening. |
| Change From Baseline to Day 90 in UNC Dry Eye Management Scale Visual Analog Scale Score | Baseline to Day 90 (±5 days) | Change from Baseline to Day 90 in the University of North Carolina Dry Eye Management Scale (UNC DEMS) Visual Analog Scale score. Scores range from 1 to 10, with higher scores indicating more severe dry-eye symptoms, greater effects on daily life, and a worse outcome. A decrease indicates improvement. |
| Change From Baseline to Day 90 in Tear Break-Up Time (TBUT) | Baseline to Day 90 (±5 days) | Change from Baseline to Day 90 in tear break-up time, measured in seconds, in the prespecified study eye. An increase indicates improvement in tear-film stability. |
| Time to First Administration of Protocol-Defined Rescue Therapy | Randomization through Day 90 | Time from randomization to the first administration of protocol-defined rescue therapy. |
| Percentage of Participants Receiving Protocol-Defined Rescue Therapy | Randomization through Day 90 | The proportion of participants receiving at least one administration of protocol-defined rescue therapy during the randomized treatment period. |
| Percentage of Participants With Protocol-Defined Treatment Failure | Randomization through Day 90 | The proportion of participants experiencing treatment failure, defined as initiation of protocol-defined rescue therapy, permanent discontinuation of assigned study treatment because it is not providing adequate benefit, or withdrawal from all further study participation because of worsening ocular GVHD signs or symptoms. |
Countries
United States
Contacts
CONTACTMarissa Harrell, PhD
Outcome results
None listed