A Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Infliximab in Subjects With Pemphigus Vulgaris Receiving Prednisone
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Participant Response to Treatment at Week 18
研究概览
简要总结
Pemphigus vulgaris (PV) is a rare skin disorder that causes blistering of the skin and mucous membranes. Infliximab is a man-made antibody used to treat certain types of immune system disorders, including rheumatoid arthritis and Crohn's disease. This study will determine if infliximab given in combination with prednisone is a safe and effective treatment for adults with PV.
详细描述
PV involves blistering of the outer layer of skin and mucous membranes, causing a separation of epidermal cells. The disease occurs when the immune system produces antibodies to specific proteins in the skin and mucous membranes; the cause for production of these autoantibodies is unknown. Infliximab is a genetically engineered monoclonal antibody directed against tumor necrosis factor (TNF)-alpha, a chemical messenger that activates an immune response. Infliximab has been used to treat other autoimmune disorders, including rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. This study will evaluate the safety and efficacy of infliximab given in combination with prednisone for the treatment of adults with PV.
This study will last 26 weeks. At study entry, all patients will be taking a stable dose of prednisone (or an equivalent corticosteroid) of 20 to 120 mg/day for at least 2 weeks prior to study entry. Patients will be randomly assigned to one of two arms: experimental or placebo comparator. The experimental treatment arm will receive infusions of infliximab, and the control arm will receive placebo. Infusions will be given at study entry and Weeks 2, 6, and 14. Before the start of each infusion, a physical exam, vital signs measurement, medical and medication history, review of a disease activity log, a skin evaluation, and blood collection will occur. During each infusion and for 1 hour postinfusion, patients' vital signs will be monitored for any adverse events. Patients will need a responsible adult to take them home after they are discharged from the treatment facility; this person should remain with the patient overnight in case any problems arise from the treatment. The patient will be contacted by phone that night and the next morning after infusion and will be asked about any adverse effects they may have experienced. Those patients that experience adverse effects may be asked to return to the treatment facility for examination. Prednisone doses may be tapered by 15 percent every 2 weeks during the study at the investigator's discretion.
There will be a total of 9 study visits until Week 26: screening, study entry, Week 2, and every 4 weeks thereafter. Each study visit will include a physical exam, vital signs measurement, medical and medication history, a review of the disease activity log and adverse events experienced since the last visit, skin assessments, and blood collection; patients will also be asked to complete a tuberculosis (TB) questionnaire. Patients will be asked to complete quality of life questionnaires at study entry and Weeks 10, 18, and 26. Skin biopsies of unaffected skin will be done at study entry and Weeks 10, 18, and 26; if patients have PV-associated lesions, additional skin biopsies of affected skin will be done at study entry and Week 18.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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
- •Positive direct immunofluorescence of patient's skin showing IgG or complement C3 protein on cell surface with histopathology of lesional skin biopsies consistent with diagnosis of pemphigus vulgaris
- •Failure to completely respond to standard steroid therapy (equivalent to prednisone 1 to 2 mg/kg/day followed by tapering)
- •Systemic corticosteroid therapy of at least 20 mg prednisone daily and no more than 120 mg/day
- •Inability to reduce systemic corticosteroid dosage below 20 mg/day for at least 8 weeks
- •Stable dosage of prednisone for at least 2 weeks prior to study entry
- •Oral/mucosal disease or skin disease. Detailed information about this criterion can be found in the protocol
- •Willing to comply with the study protocol
- •Willing to use acceptable means of contraception for the duration of the study and for 6 months after the end of the study
排除标准
- •Positive tuberculosis (TB) test within 1 month prior to first administration of study drug
- •History of latent or active TB prior to screening
- •Signs or symptoms suggestive of TB disease by medical history or physical examination within 3 months prior to first administration of study drug
- •Posterior/anterior/lateral chest radiograph within 3 months prior to screening showing evidence of cancer, infection, or abnormalities (apical scarring) suggestive of previous TB
- •Serious infection, hospitalization for an infection, or treatment with intravenous (IV) antibiotics for an infection within 2 months prior to screening. Patients who have had less serious infections are eligible for this study at the discretion of the investigator.
- •History or presence of opportunistic infections within 6 months prior to screening
- •History of receiving human/murine recombinant products
- •Known allergy to murine products or other chimeric proteins
- •Human immunodeficiency virus (HIV) infected
- •Chronic hepatitis B or hepatitis C virus infection
- •History of hepatitis C virus infection
- •Cancer within the 5 years prior to study entry. Patients with completely resected non-melanoma skin cancers are not excluded.
- •History or presence of congestive heart failure
- •History or presence of seizure or demyelinating disorder
- •History of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis
- •Received a Bacillus Calmette-Guerin (BCG) vaccine within 12 months of screening
- •History of lymphoproliferative disease, including lymphoma or signs and symptoms of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location or enlarged spleen
- •Current signs or symptoms of severe progressive or uncontrolled kidney, liver, blood, gastrointestinal, endocrine, lung, heart, neurologic, or cerebral disease
- •Have had chronic or recurrent infectious disease including, but not limited to, chronic kidney infection, chronic chest infection, sinusitis, recurrent urinary tract infection, infected skin wound, or ulcer
- •Previous treatment with infliximab, other monoclonal antibodies, or antibody fragments
- •Previous treatment with etanercept or other anti-tumor necrosis factor (TNF) agents in the 3 months prior to screening
- •Treatment with methotrexate, azathioprine, mycophenolate mofetil, plasmapheresis, IV immunoglobulin, pulse systemic corticosteroids, or other systemic immunosuppressive agents within the 4 weeks prior to study entry
- •History of alcohol or drug abuse within the 3 years prior to study entry
- •History of noncompliance to medical regimens
- •History of a systemic inflammatory disease other than pemphigus vulgaris
- •History of a medical condition that would interfere with participation or increase the risk to the participant
- •Unable or unwilling to undergo blood draws because of poor tolerability or lack of easy access
- •Use of any investigational drug within 30 days prior to screening OR within 5 half-lives of the investigational agent, whichever is longer
- •Participation in another investigative clinical trial
- •Presence of transplanted solid organ. Participants who have received a corneal transplant more than 3 months prior to screening are not excluded.
- •Require certain medications
- •Other conditions or circumstances that could interfere with participant's adherence to the study requirements
- •Pregnancy, breastfeeding, or plans to become pregnant
研究组 & 干预措施
Infliximab
Participants are randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a masked (blinded) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
干预措施: Infliximab (Drug)
Placebo Comparator
Participants are randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a masked (blinded) fashion. Refer to section titled, "Detailed Description" for additional treatment information.
干预措施: Placebo Comparator (Other)
结局指标
主要结局
Participant Response to Treatment at Week 18
时间窗: Baseline to Week 18
Participants classified as responders at Week 18 had: 1. Achieved a prednisone dosage \<= 25% of the initial starting dose or \<= 10 mg/day (whichever is greater), and 2. Had no new blisters within the previous 4 weeks.
Treatment-Related Adverse Events >= Grade 3 On or Before Week 18
时间窗: Baseline to Week 18
Grades were based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. An adverse event (AE) was considered treatment-related if it was classified as unlikely, possibly, probably, or definitely related to study treatment. Participants who experienced at least one treatment-related, grade 3 or higher AE were counted only once. AEs of skin including rash, skin ulceration, and chelitis as defined by the NCI-CTCAE V3.0 System Organ Class of "Skin and Subcutaneous Tissues Disorders" were excluded.
次要结局
- Participant Modified Response Status at Week 18(Baseline to Week 18)
- Participant Response to Treatment at Week 18(Baseline to Week 18)
- Participant Time to Cessation of New Blisters(Baseline to Week 26)
- Time to 80% Lesion Healing(Baseline to Week 26)
- Total Prednisone Dosage Required for Participants to Achieve Cessation of New Blisters(Baseline to Week 26)
- Total Prednisone Dosage Required for Participants to Achieve 80% Healing of Existing Erosions(Baseline to Week 26)
- Participant Health Related Quality of Life (Medical Outcome Study Short Form 36) Score Changes From Baseline to Week 18(Baseline to Week 18)
- Participant Dermatology-Related Quality of Life Changes From Baseline to Week 18(Baseline to Week 18)
- Participant Duration of Clinical Response(Baseline to Week 26)
- Participants Who Experienced Severe Infusion Reactions(Baseline to Week 26)
- Participants Who Experienced Severe Infectious Complications(Baseline to Week 26)
- Adverse Events Resulting in Treatment Discontinuation(Baseline to Week 26)
- Participant Pemphigus Vulgaris Disease Activity Score(Baseline to Week 26)