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

该2期临床试验于2013年11月15日启动，我们已经招募并治疗了11例严重眼GVHD患者。该研究设计为双掩模、安慰剂对照和随机6个月的交叉研究，其中安慰剂或自体血清滴眼液（ASED）使用3个月（第一阶段），然后切换到另一种滴眼液再使用3个月（第二阶段）。然后将为患者提供实际的ASED（开放标签阶段3），直到研究完成和终止。4名患者已经完成了为期6个月的交叉研究阶段（第1期和第2期），现在正在使用实际的自体血清滴眼液（研究的开放标签第3期）。所有完成第一阶段和第二阶段的4名患者都确信，在使用滴眼液的头几周内，他们知道自己在研究的哪一组（无论是安慰剂还是ASED），因为其中一种滴眼液明显缓解了症状。现在在第三阶段，使用开放标签的染色滴剂，他们声称干眼症状得到了明显的主观缓解。

This Phase 2 clinical trial was activated on November 15, 2013 and we have recruited and treated 11 patients with severe ocular GVHD. The study was designed to be a double masked, placebo controlled and randomized 6 month cross over study where either a placebo or the autologous serum eye drop (ASED) is used for 3 months (Phase 1), then switched to the other drop for another 3 months (Phase 2). Then the patient will be provided with the actual ASED (Open label phase 3) until the completion and termination of the study. 4 patients have completed the 6 month cross over study phases (Phases 1 and 2) and are now using the actual autologous serum eye drops (unmasked, open label Phase 3 of the study). All 4 who have completed Phases 1 and 2 are convinced that they knew which arm of the study they were in (whether placebo or ASED), within the first weeks of using the eye drops due to the marked relief from symptoms from one of the drops. Now in Phase 3, using the open label ASED dye drops, they now claim significant subjective relief of their dry eye symptoms. Our close collaboration with the Department of Transfusion Medicine (also called the NIH Blood Bank) and the NIH Clinical Center Pharmacy has allowed for smooth production of the ASED inspite of the complex requirements imposed by the FDA and the often very poor health of the GVHD patients. One important feature of the FDA approved study is the use of non- preserved ASED in dropperrettes which are frozen and used only once after thawing, and then discarded, to avoid spoilage as well as contamination. Since 4 such dropperrettes are used every day, the NIH Pharmacy has to make up thousands of such dropperrettes for every patient. We needed to make several amendments to refine the Protocol, to make adjustments and give more leeway for the NIH Blood Bank and Pharmacy to extend the windows for the complex steps in the production of the eye drops and stay within the requirements of FDA. This is helpful information for all blood banks and pharmacies that will be making these eye drops in the future. One patient who was very ill and suffered from GVHD of the lungs, passed away before she can start the ASED but after she was screened and enrolled in the study. She went for a short visit to her home in South America but developed pneumonia and passed away in her sleep. This shows how frail Bone Marrow Transplantation patients are, and how they can develop multi-organ complications from GVHD. In summary, we are continuing to recruit and treat severe ocular GVHD patients who have severe dry eye symptoms in this clinical trial and are encouraged by the enthusiastic participation of the first few patients.