A Randomized, Double Blind, Placebo Controlled Clinical Trial to Evaluate the Efficacy of Abatacept Costimulatory Blockade in the Treatment of Alopecia Totalis/Universalis
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 主要终点
- The study's primary endpoint will be the proportion of responders after 6 months of treatment, defined as 50% or greater hair re-growth from baseline as assessed by Severity of Alopecia Tool (SALT) score at week 24.
研究概览
简要总结
Will Abatacept reduce priming of the hair follicle specific T cells and thereby reduce hair follicle associated infiltration and improve hair growth.
This is a double blind placebo controlled study to test the safety and efficacy of Abatacept in the treatment of 64 subjects diagnosed with alopecia totalis or alopecia universalis. Subjects will be randomized 1:1 to the placebo or treatment arm and will receive 6 months of treatment with the study medication or placebo, followed by a 6 month observational period.
详细描述
Alopecia Areata is a common autoimmune disease, affecting 1% of the general population resulting from autoimmune attack on the hair follicles and usually presents with patchy hair loss. One third of these patients will experience spontaneous remissions within the first year. However many patients will develop waxing and waning disease with some progressing to alopecia totalis (total scalp hair loss) or alopecia universalis (loss of all body hair). This population that suffers from a disfiguring disease represents a significant unmet medical need. Alopecia totalis/universalis seldom, if ever, remits spontaneously or with current treatment and is classified by the FDA as an Orphan Indication.
There is no FDA approved drug for alopecia areata. A recent Cochrane report concluded that there was no evidence based support for any intervention in this disease. Standard of care remains observation for mild disease and lesional/oral steroids for more advanced cases.
Abatacept is a soluble human fusion protein that selectively modulates the costimulatory signal required for full T-cell activation. It is approved for the treatment of moderately to severely active rheumatoid arthritis. It is also approved for the treatment of moderately to severely active polyarticular juvenile idiopathic arthritis in children 6 years of age or older. Abatacept is a lyophilized powder administered as a 30 minute intravenous infusion. Dosage, as in rheumatoid arthritis, is weight based and is fixed throughout the course of treatment. Abatacept or placebo will be administered as a 30 minute intravenous infusion at baseline, weeks 2, 4, and every 4 weeks for 5 cycles (weeks 8, 12, 16, 20) for a total treatment period of 6 months. There will be a 6 month observational period following the treatment period.
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, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be between 18 and 75 years of age.
- •Must have a diagnosis of alopecia totalis or alopecia universalis
- •Must have >75% total scalp hair loss at baseline as measured using the SALT score.
- •Duration of hair loss must be between 3 to 12 months.
- •There may be no evidence of regrowth present at baseline.
- •Subjects may be naïve to treatment or unresponsive to intralesional (IL) steroids or other treatments for alopecia areata.
- •Must be willing to avoid live vaccines while on the study medication, and within 3 months of its discontinuation.
排除标准
- •Patients with a history of or active skin disease on the scalp such as psoriasis or seborrheic dermatitis.
- •Patients in whom the diagnosis of alopecia areata is in question.
- •Patients with active medical conditions or malignancies (except adequately treated basal or squamous cell carcinoma) that in the opinion of the investigator would increase the risks associated with study participation, including patients with a history of recurrent infections.
- •Patients who monitor their blood glucose levels using glucose dehydrogenase pyrrologuinolinequinone (GDH-PQQ) test strips. Blood glucose monitoring using other methods that do not react with maltose, such as the glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase test methods are permitted.
- •Patients taking TNF antagonists or other biological therapy such as anakinra.
- •Women of childbearing potential who are unable or unwilling to use two forms of birth control for the study duration.
- •Women who are pregnant or nursing.
- •Patients known to be HIV or hepatitis B or C positive.
- •Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening.
- •Patients with latent Mycobacterium tuberculosis infection as indicated by a positive Purified Protein Derivative [PPD] skin test. Subjects with a positive PPD skin test and documented completion of treatment per standard medical practice for latent TB are eligible. Subjects with a positive PPD skin test and not treated or no documentation of completion of treatment are ineligible.
- •History of incompletely treated Mycobacterium tuberculosis infection as indicated by:
- •Subject's medical records documenting incomplete treatment for Mycobacterium tuberculosis
- •Subject's self-reported history of incomplete treatment for Mycobacterium tuberculosis
- •Patients with evidence of infection or skin cancer in the treated areas.
- •Patients with history or evidence of hematopoietic abnormality.
- •Patients with history of immunosuppression or history of recurrent serious infections.
- •Patients with a history or likely diagnosis of COPD
- •Patients unwilling or unable to discontinue treatments known to affect hair regrowth in alopecia areata.
- •Patients who have been treated with intralesional steroids, systemic steroids, anthralin, squaric acid, DPCP (diphenylcycloprophenone), protopic, minoxidil or other medication which in the opinion of the investigator may affect hair regrowth within one month of the baseline visit.
研究组 & 干预措施
Abatacept
Abatacept administered as a 30 minute intravenous infusion
干预措施: Abatacept (Drug)
Inactive infusion
Placebo will be administered as a 30 minute intravenous infusion.
干预措施: Inactive infusion (Drug)
结局指标
主要结局
The study's primary endpoint will be the proportion of responders after 6 months of treatment, defined as 50% or greater hair re-growth from baseline as assessed by Severity of Alopecia Tool (SALT) score at week 24.
时间窗: 24 weeks
The study's primary endpoint of this intent to treat trial will be the proportion of responders in the treated compared to the control group after 6 months of treatment, defined as 50% or greater hair re-growth from baseline as assessed by Severity of Alopecia Tool (SALT) score at week 24. This is a relatively strict definition for defining responders and non-responders and was chosen to minimize responses in the 'vehicle' arm, in which fewer than 10% are expected to achieve this magnitude of hair re-growth spontaneously.
次要结局
- Percent hair regrowth from baseline determined by SALT at weeks 4, 8, 12, 20, and 24 during treatment phase and at weeks 30, 36, 42 and 48 during the observational phase.(24 weeks of treatment and 18 weeks observational phase)
研究者
Julian M. Mackay-Wiggan
Assistant Clinical Professor of Dermatology
Columbia University