Clinical Trial: A Randomized, Controlled, Double-Masked, Clinical Trial of Autologous Serum Eye Drops for Severe Ocular Chronic Graft-versus-Host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients
Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional
Official Title: A Randomized, Controlled, Double-Masked, Clinical Trial of Autologous Serum Eye Drops for Severe Ocular Chronic Graft-versus-Host Disease (GVHD) in Hematopoietic Stem Cell
Brief Summary:
Some eye diseases can be helped by eye drops made from a person's own blood. These eye drops are called autologous serum eye drops, or ASEDs. ASEDs have been studied in only a few people with graft vs. host disease (GVHD) affecting the eye and were found to be helpful with few side effects.
The purpose of this study was to determine whether ASEDs are safe and more effective than control (normal saline) and can help with eye symptoms in people with severe chronic eye GVHD.
Each participant in this study was to have blood drawn to prepare ASEDs specifically for the participant. Each participant was scheduled to receive ASEDs for 3 months and placebo eye drops (salt water) for 3 months. Participants did not know when they were receiving the ASEDs and when they were receiving placebo eye drops.
Detailed Summary:
Objective:
A common, serious and debilitating long term complication of hematopoietic stem cell transplant (HCST) is chronic graft-versus-host disease (GVHD). Ocular GVHD develops in up to 85% of patients with chronic GVHD. It is characterized by progressive keratitis sicca and cicatrizing ocular inflammatory surface disease with T cell mediated damage to conjunctival and corneal epithelium and lacrimal tissue. Various medical and surgical treatments have been used, such as various lubricating agents, steroid drops and ointments, cyclosporin drops, punctal plugs or cautery and partial tarsorrhaphy. However, in severe cases, none offer acceptable, long-lasting relief from pain, irritation, dryness and diminished vision associated with ocular GVHD. An alternative treatment that has previously been safely investigated is autologous serum eye drops (ASEDs). The objective of this study was to determine whether ASEDs are more effective than control (normal saline) in the treatment of severe chronic ocular GVHD in HSCT patients unresponsive to standard medical treatment.
Study Population:
Eighteen post-HSCT patients with severe ocular GVHD unresponsive to standard medical treatment were enrolled. Initially, 34 post-HSCT patients with severe ocular GVHD unresponsive to standard medical treatment were to be enrolled. However, only 18 enrolled, as the investigational product (IP) was no longer provided to participants as of June 2015 due to manufacturing issues.
Design:
This was a Phase 2, randomized, double-masked, controlled, crossover, single-center study to investigate ASEDs in participants with severe chronic ocular GVHD. During the initial crossover phase of the study, participan
Sponsor: National Eye Institute (NEI)
Current Primary Outcome: Proportion of Participants Who Experienced a ≥ 50% Reduction in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH/National Eye Institute (NEI) Visual Analogue Scale in the Study Eye From Baseline to Month 3. [ Time Frame: Baseline and 3 months ]
Original Primary Outcome: The primary outcome is the proportion of participants experiencing a > = 50% reduction in the combined score of the modified Oxford punctate keratopathy grading and the NIH/NEI visual analogue scale in the study eye from baseline to Month 3. [ Time Frame: 3 years ]
Current Secondary Outcome:
- Number of Systemic and Ocular Toxicities and Adverse Events [ Time Frame: Study Duration, up to 24 months ]
- Number of Participants Withdrawn From the Study Treatment Due to Vision Loss, Adverse Events or Treatment Failure [ Time Frame: Study Duration, up to 24 months ]
- Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Study Eye at 3 Months Compared to Baseline [ Time Frame: Baseline and 3 Months ]Oxford punctate keratopathy is an objective measure from 0-5 (cornea only) and the NIH/NEI visual analogue scale is a subjective grading performed by the participant regarding his/her ocular dryness, redness and irritation (scored 0-3 for each symptom with 0 = none, 1 = mild, 2 = moderate and 3 = severe for a total score between 0-9). The combined score was a number between 0-14 with the higher number representing a worse outcome.
- Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Fellow Eye at 3 Months Compared to Baseline [ Time Frame: Baseline and 3 Months ]The fellow eye is the untreated eye. Oxford punctate keratopathy is an objective measure from 0-5 (cornea only) and the NIH/NEI visual analogue scale is a subjective grading performed by the participant regarding his/her ocular dryness, redness and irritation (scored 0-3 for each symptom with 0 = none, 1 = mild, 2 = moderate and 3 = severe for a total score between 0-9). The combined score was a number between 0-14 with the higher number representing a worse outcome.
- Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Study Eye at 6 Months Compared to Baseline [ Time Frame: Baseline and 6 Months ]Oxford punctate keratopathy is an objective measure from 0-5 (cornea only) and the NIH/NEI visual analogue scale is a subjective grading performed by the participant regarding his/her ocular dryness, redness and irritation (scored 0-3 for each symptom with 0 = none, 1 = mild, 2 = moderate and 3 = severe for a total score between 0-9). The combined score was a number between 0-14 with the higher number representing a worse outcome.
- Mean Change in the Combined Score of the Modified Oxford Punctate Keratopathy Grading and the NIH Visual Analogue Scale in the Fellow Eye at 6 Months Compared to Baseline [ Time Frame: Baseline and 6 Months ]The fellow eye is the untreated eye. Oxford punctate keratopathy is an objective measure from 0-5 (cornea only) and the NIH/NEI visual analogue scale is a subjective grading performed by the participant regarding his/her ocular dryness, redness and irritation (scored 0-3 for each symptom with 0 = none, 1 = mild, 2 = moderate and 3 = severe for a total score between 0-9). The combined score was a number between 0-14 with the higher number representing a worse outcome.
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Study Eye at 3 Months Compared to Baseline [ Time Frame: Baseline and 3 Months ]
The CAS score is the sum of the scores on three separate assessments: Schirmer's tear test without anesthesia, punctate keratopathy and conjunctival inflammation and scarring (scored according to Robinson et. al*). Each assessment was scored 0-3 with 0 = none, 1 = mild, 2 = moderate and 3 = severe. The higher values represent a worse outcome. The CAS score was a number between 0-9 with the higher number representing a worse outcome.
*Robinson MR, Lee SS, Rubin BI, Wayne AS, Pavletic SZ, Bishop MR, Childs R, Barrett AJ, Csaky KG. Topical Corticosteroid Therapy for Cicatricial Conjunctivitis Associated with Chronic Graft Versus Host Disease. Bone Marrow Transplant. 2004; 18:567-9.
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Fellow Eye at 3 Months Compared to Baseline [ Time Frame: Baseline and 3 Months ]
The fellow eye is the untreated eye. The CAS score is the sum of the scores on three separate assessments: Schirmer's tear test without anesthesia, punctate keratopathy and conjunctival inflammation and scarring (scored according to Robinson et. al*). Each assessment was scored 0-3 with 0 = none, 1 = mild, 2 = moderate and 3 = severe. The higher values represent a worse outcome. The CAS score was a number between 0-9 with the higher number representing a worse outcome.
*Robinson MR, Lee SS, Rubin BI, Wayne AS, Pavletic SZ, Bishop MR, Childs R, Barrett AJ, Csaky KG. Topical Corticosteroid Therapy for Cicatricial Conjunctivitis Associated with Chronic Graft Versus Host Disease. Bone Marrow Transplant. 2004; 18:567-9.
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Study Eye at 6 Months Compared to Baseline [ Time Frame: Baseline and 6 Months ]
The CAS score is the sum of the scores on th
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: October 23, 2013
Date Started: November 2013
Date Completion:
Last Updated: October 26, 2016
Last Verified: October 2016
