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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
ASEDs - Saline
Participants administer autologous serum eye drops (ASEDs) daily for the first three months, then crossover to administer control (normal saline) eye drops daily beginning at Month 3 through Month 6.
干预措施: ASEDs (Drug)
ASEDs - Saline
Participants administer autologous serum eye drops (ASEDs) daily for the first three months, then crossover to administer control (normal saline) eye drops daily beginning at Month 3 through Month 6.
干预措施: Saline (Drug)
Saline - ASEDs
Participants administer control (normal saline) eye drops daily for the first three months, then crossover to administer autologous serum eye drops (ASEDs) daily beginning at Month 3 through Month 6.
干预措施: ASEDs (Drug)
Saline - ASEDs
Participants administer control (normal saline) eye drops daily for the first three months, then crossover to administer autologous serum eye drops (ASEDs) daily beginning at Month 3 through Month 6.
干预措施: Saline (Drug)
结局指标
主要结局
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.
时间窗: Baseline and 3 months
A ≥ 50% reduction in the combined score was considered a treatment success. While the design is a crossover study, the primary outcome was assessed after the first period at Month 3. 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.
次要结局
- Number of Participants Withdrawn From the Study Treatment Due to Vision Loss, Adverse Events or Treatment Failure(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(Baseline and 3 Months)
- Number of Systemic and Ocular Toxicities and Adverse Events(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 Fellow Eye at 3 Months Compared to Baseline(Baseline and 3 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 6 Months Compared to Baseline(Baseline and 6 Months)
- 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(Baseline and 6 Months)
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Study Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Fellow Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Study Eye at 6 Months Compared to Baseline(Baseline and 6 Months)
- Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 6 Months Compared to Baseline(Baseline and 6 Months)
- Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 6 Months Compared to Baseline.(Baseline and 6 Months)
- Mean Change in Tear Stability (Tear Break-up Time) in the Fellow Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in Tear Stability (Tear Break-up Time) in the Study Eye at 6 Months Compared to Baseline(Baseline and 6 Months)
- Mean Change in Tear Stability (Tear Break-up Time) in the Fellow Eye at 6 Months Compared to Baseline(Baseline and 6 Months)
- Mean Change in Tear Composition (Tear Osmolarity) in the Study Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in Tear Composition (Tear Osmolarity) in the Study Eye at 6 Months Compared to Baseline(Baseline and 6 Months)
- Mean Change in the Chronic Ocular GVHD Composite Assessment Scale (CAS) Score in the Fellow Eye at 6 Months Compared to Baseline(Baseline and 6 Months)
- Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Study Eye at 3 Months Compared to Baseline.(Baseline and 3 Months)
- Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) in the Fellow Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in Tear Stability (Tear Break-up Time) in the Study Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in Tear Composition (Tear Osmolarity) in the Fellow Eye at 3 Months Compared to Baseline(Baseline and 3 Months)
- Mean Change in Tear Composition (Tear Osmolarity) in the Fellow Eye at 6 Months Compared to Baseline(Baseline and 6 Months)