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

自体血清滴眼液治疗造血干细胞移植 (HSCT) 患者严重眼部慢性移植物抗宿主病 (GVHD) 的随机、对照、双盲临床试验

• 批准号: 8938373
• 负责人: Manuel B Datiles
• 金额: $ 4.85万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8938373
• 关键词: Amendment; Anemia; Artificial Tears; Autologous; Back; Blood; Blood Banks; Bone Marrow Transplantation; Case Study; Cells; Chronic Disease; Chronic Granulomatous Disease; Clinical; Clinical Trials; Collaborations; Complex; Contact Lenses; Controlled Clinical Trials; Cross-Over Studies; Cyclosporine; Disease; Drops; Dry Eye Syndromes; Dyes; Enrollment; Eye; Eyedrops; FDA approved; Freezing; Future; HIV; Health; Hematopoietic Neoplasms; Hematopoietic stem cells; Home environment; Infection; Life; Lung; Mainstreaming; Malignant Neoplasms; Masks; Medicine; Methods; Ointments; Organ; Patients; Pharmacy facility; Phase; Phase II Clinical Trials; Placebo Control; Placebos; Pneumonia; Production; Protocols documentation; Publishing; Quality of life; Randomized; Recruitment Activity; Reporting; Running; Safety; Series; Serum; Sickle Cell Anemia; Sleep; Solid Neoplasm; South America; Stem cell transplant; Steroids; Symptoms; Transfusion; Transplant Recipients; United States National Institutes of Health; Visit; Work; arm; chronic graft versus host disease; cost; design; eye dryness; graft vs host disease; leukemia; open label; phase 3 study; prevent; success; sunglasses

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.

这项2期临床试验于2013年11月15日启动，我们招募并治疗了11例严重眼部GVHD患者。本研究设计为双盲、安慰剂对照和随机6个月交叉研究，其中安慰剂或自体血清滴眼液（ASED）使用3个月（1期），然后改用另一种滴眼液再使用3个月（2期）。然后，将向患者提供实际ASED（开放标签III期），直至研究完成和终止。4例患者已完成6个月交叉研究阶段（阶段1和阶段2），目前正在使用实际的自体血清滴眼液（研究的非盲态、开放标签阶段3）。所有4名完成1期和2期的受试者都确信，由于其中一种滴眼液的症状明显缓解，他们在使用滴眼液的前几周内知道自己处于研究的哪个组（无论是安慰剂组还是ASED组）。现在在第3阶段，使用开放标签的ASED染料滴剂，他们现在声称他们的干眼症症状得到了显着的主观缓解。 我们与输血医学系（也称为NIH血库）和NIH临床中心药房的密切合作，使ASED的顺利生产成为可能，尽管FDA提出了复杂的要求，GVHD患者的健康状况往往很差。FDA批准的研究的一个重要特征是在冷冻的滴管中使用非保存的ASED，解冻后仅使用一次，然后丢弃，以避免腐败和污染。由于每天使用4个这样的dropperrettes，NIH药房必须为每个患者补充数千个这样的dropperrettes。我们需要进行几次修订，以完善方案，进行调整，并为NIH血库和药房提供更多的回旋余地，以延长滴眼液生产中复杂步骤的窗口，并保持在FDA的要求范围内。这是有用的信息，为所有血库和药房，将使这些滴眼液在未来。 1例病情严重并患有肺部GVHD的患者在开始ASED前去世，但在她接受筛选并入组研究后去世。她去了南美的家做了一次短暂的访问，但却患上了肺炎，在睡梦中去世。这表明骨髓移植患者是多么虚弱，以及他们如何从GVHD发展多器官并发症。 总之，我们正在继续招募和治疗在本临床试验中有严重干眼症症状的严重眼部GVHD患者，并受到前几名患者热情参与的鼓舞。