Advanced Magnetic Resonance Imaging Measures of Repair in Alemtuzumab Treated Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Changes in normal appearing white matter from baseline through month 24.
研究概览
简要总结
There are two parts to this investigator sponsored trial (IST):
- To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
- To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.
详细描述
Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the Central Nervous System (CNS). There are many forms of MS; although the majority are Relapsing Remitting (RRMS) representing approximately 80% of the cases. The disease appears to be more inflammatory in RRMS as manifested by an increase in Gadolinium (Gd) enhancement on MRI and an increase in inflammatory bio-assay markers.
Alemtuzumab; a humanized monoclonal antibody that targets the CD52 molecule present on T and B lymphocytes, natural killer (NK) cells, and monocytes and macrophages; effects rapid and sustained lymphocyte depletion and is approved for the treatment of B-cell chronic lymphocytic leukemia in many countries under the names CAMPATH or MabCAMPATH.
There are two parts to this Investigator Sponsored Trial (IST):
- To perform advanced serial MRI studies on patients initiating alemtuzumab therapy.
- To provide serum samples for the University of Southern California (USC) ICAM125 lymphocyte recovery study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed, informed consent form
- •Age 18 to 50 years old (inclusive)
- •Diagnosis of MS per update of McDonald criteria, and cranial MRI scan demonstrating white matter lesions attributable to MS within 10 years of screening
- •Onset of MS symptoms within 15 years of screening
- •Neurostatus (EDSS) score 0.0 to 5.0 (inclusive)
- •2 MS attacks (first episode or relapse) occurring in the 24 months prior to screening, with 1 attack in the 12 months prior to screening, with objective neurological signs confirmed by a physician.
排除标准
- •Received prior therapy for MS other than corticosteroids within 28 days of screening; e.g., interferon's, IV immunoglobulin, and glatiramer acetate
- •Exposure to natalizumab within 6 months of screening
- •Any prior exposure to mitoxantrone, mycophenolate mofetil, azathioprine, cladribine, cyclophosphamide, cyclosporine A, methotrexate, rituximab, or any other immunosuppressive agent other than systemic corticosteroid treatment
- •Has any progressive form of MS
- •History of malignancy (exception for basal cell skin carcinoma)
- •Previous hypersensitivity reaction to other immunoglobulin product
- •Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
- •CD4+, CD8+, or CD19+ (i.e., absolute CD3+CD4+, CD3+CD8+, or CD19+/mm3) count <LLN at Screening; if abnormal cell count(s) return to within normal limits, eligibility may be reassessed
- •Seropositivity for human immunodeficiency virus (HIV)
- •Significant autoimmune disease (e.g, immune cytopenias, rheumatoid arthritis, systemic lupus erythematosus, other connective tissue disorders; vasculitis; inflammatory bowel disease; severe psoriasis)
- •Presence of anti-thyroid stimulating hormone (TSH) receptor (TSHR) antibodies
- •Active infection
- •Latent tuberculosis unless effective anti-tuberculosis therapy has been completed, or active tuberculosis.
- •Infection with hepatitis B virus or hepatitis C virus
- •Of childbearing potential with a positive serum pregnancy test
- •Unwilling to agree to use a reliable and acceptable contraceptive method throughout the study period
- •Major psychiatric disorder that is not adequately controlled by treatment
- •Epileptic seizures that are not adequately controlled by treatment
- •Major systemic disease or other illness that would, in the opinion of the Investigator, compromise patient safety or interfere with the interpretation of study results
- •Medical, psychiatric, cognitive, or other conditions
- •Confirmed platelet count the lower limit of normal (LLN) of the evaluating laboratory at Screening or documented at 100,000/L within the past year on a sample without clumping
- •Prior history of invasive fungal infections
- •Cervical high risk human papilloma virus (HPV) positivity or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS).
- •Seropositive for Trypanosoma cruzi or the Human T-lymphotropic virus type I or type II (HTLV-I/II) (testing required in endemic regions only)
- •Any other illness or infection (latent or active) that, in the Investigator's opinion, could be exacerbated by alemtuzumab treatment
- •Any hepatic or renal function value grade 2 or higher at Screening, with the exception of hyperbilirubinemia due to Gilbert's syndrome.
研究组 & 干预措施
MabCampath-1h
Single arm, single cohort study, all subjects will be dosed with alemtuzumab.
干预措施: MabCampath-1h (Drug)
结局指标
主要结局
Changes in normal appearing white matter from baseline through month 24.
时间窗: 24 months
The MRI study is designed to identify possible mechanisms by which alemtuzumab acts to protect the brain from inflammation and how it may enhance repair through remyelination.
次要结局
- To identify specific changes in T cell subsets and functions in Relapsing Remitting Multiple Sclerosis from baseline through month 48.(48 months)
研究者
Anthony Traboulsee
Principal Investigator
University of British Columbia