A Phase 2, Open Label Single Arm Study for Evaluating Safety & Efficacy of Apremilast in the Treatment of Cutaneous Disease in Patients With Recalcitrant Dermatomyositis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- The Primary Endpoint Analysis Would be Overall Response Rate Measured by the Number of Participants Experiencing at Least 4 Points Decrease in CDASI Activity Score at 3 Months.
研究概览
简要总结
With limited treatment options available for dermatomyositis, the investigators hypothesize that apremilast, a phosphodiesterase-4 (PDE-4) inhibitor, is a safe and efficacious add-on treatment in patients with refractory cutaneous dermatomyositis.
The study will investigate the efficacy, safety and toxicity of apremilast given at 30 mg twice daily to patients with refractory cutaneous dermatomyositis. Clinical response will be assessed at 1 and 3 months. Patients will also be evaluated for durability of their response for up to 6 months.
Treatment will be monitored with frequent clinical visits (0, 1, 3 and 6 months) and blood tests (CBC, CMP, creatine kinase, aldolase). Treatment will be discontinued at disease progression or unacceptable adverse events. Disease progression is defined as 4 points increase in the cutaneous dermatomyositis disease area and severity index (CDASI) score, worsening of muscle disease by manual muscle testing (MMT-8) score and 5 points increase in dermatomyositis life quality index (DLQI).
5 mm skin biopsies from lesional skin will be performed before treatment with apremilast and after 3 months of treatment for gene expression profiling and confirmatory immunohistochemical stains.
详细描述
- Sponsor Name (PI): Carole Bitar, MD
- Sub-PI: Erin Boh, MD, PhD; Brittany Stumpf, MD; Collaborator: Nakhle Saba, MD
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of Participants Sites: 1, Tulane University 4: Participant Countries: United States
II. PRODUCT INFORMATION
- Study Title: A phase 2, open label single arm study for evaluating safety & efficacy of apremilast in the treatment of cutaneous disease in patients with recalcitrant dermatomyositis.
- Clinical Phase: Phase II clinical trial
- Primary Celgene Product: Apremilast
III. CONCEPT DESIGN AND RATIONAL
- Therapeutic Area: Immunology
- Specialty: Connective tissue disease
- Disease State: Dermatomyositis
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must understand the risks and the benefits/purpose of the study and provide signed and dated informed consent.
- •Must be 18 years at time of signing the informed consent form.
- •Willing to participate in all required evaluations and procedures in the study including the ability to swallow pills without difficulty.
- •Patients must have a diagnosis of DM based upon the characteristic cutaneous findings proposed by Sontheimer[6] and/or a skin biopsy consistent with DM.
- •Patients must be candidate for systemic therapy for their DM skin disease defined by inadequate response to aggressive sun protection along with the use of potent topical corticosteroids and/or immunomodulators.
- •Patients with a diagnosis of dermatomyositis on steroid-sparing agent and/or systemic steroids (maximum dose of prednisone 1mg/Kg) and still having cutaneous disease activity of at least 5 on the CDASI scale.
- •If on immunosuppressive treatments and/or steroids, patients must be on stable doses for at least 4 weeks (28 days).
- •Patients must undergo age appropriate cancer screening.
- •Females of childbearing potential (FCBP) must have a negative pregnancy test at screening (day 0 of the study and every month throughout the study). While on investigational product and for at least 28 days after taking the last dose of investigational product.
排除标准
- •Increasing or changing dose of topical therapy within 14 days of study day 0 (including but not limited to topical corticosteroids, tacrolimus, pimecrolimus).
- •Increasing or changing systemic steroids dosing within 28 days of study day
- •Increasing or changing dosing for concurrent therapy agents within 28 days or 5 half-lives of the biologic agent, whichever is longer, before study day 0: methotrexate, azathioprine, mycophenolate mofetil, hydroxychloroquine, dapsone, leflunomide, cyclosporine, biologic agents (anti-TNFs), IVIG, rituximab.
- •History of any clinically significant (as determined by the investigators) cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic, or other major uncontrolled disease.
- •Any condition, including the presence of laboratory abnormalities, which places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Pregnant or breastfeeding.
- •Untreated Latent Mycobacterium tuberculosis infection or active tuberculosis infection as indicated by a positive Purified Protein Derivative (PPD) skin test or T-spot.
- •Any condition, including the presence of laboratory abnormalities that places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
- •Patients with acute dermatomyositis onset and rapid progression of muscle disease or significant systemic involvement including pulmonary diseases associated with DM.
- •Prior major surgery or major life-threatening medical illness within 2 weeks.
- •Inflammatory bowel disease, malabsorption or any other gastrointestinal motility disorders that limit the absorption of the study drug.
- •Active hepatitis B or C infection with detectible viral nucleic acid in the blood or known Human Immunodeficiency Virus (HIV) positivity.
- •Prior history of suicide attempt at any time in the patient's lifetime prior to screening or randomization, or major psychiatric illness requiring hospitalization within the last 3 years.
- •Active substance abuse or a history of substance abuse within 6 months prior to screening.
- •Use of any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
- •Prior treatment with apremilast.
- •Any severe systemic illness requiring IV antibiotics within the two weeks prior to initiation of the study drug.
- •Malignancy or history of malignancy within the past four years, except for:
- •treated [ie, cured] basal cell or squamous cell in situ skin carcinomas;
- •treated [ie, cured] cervical intraepithelial neoplasia (CIN) or carcinoma in situ of cervix with no evidence of recurrence within the previous 4 years.
研究组 & 干预措施
Dermatomyositis patients with refractory cutaneous disease
Patients with dermatomyositis and refractory skin disease on steroids and one steroid-sparing agent.
干预措施: Apremilast 30mg (Drug)
结局指标
主要结局
The Primary Endpoint Analysis Would be Overall Response Rate Measured by the Number of Participants Experiencing at Least 4 Points Decrease in CDASI Activity Score at 3 Months.
时间窗: Data collected at 3 months after baseline visit
Cutaneous dermatomyositis disease area and severity index (CDASI) activity score is a validated tool to measure skin disease activity in dermatomyositis. The overall response rate (ORR) includes partial and complete responses. Complete response is defined by a CDASI activity score of zero. Partial response is defined by a decrease of CDASI activity score of at least 4 points. Calculation is performed as the CDASI activity score at 3 month(s) minus the score at baseline. Missing data will be handled using the last observation carried forward approach (LOCF). CDASI activity score: Units on a scale from 0-100. Higher scores represent worse outcome.
次要结局
- 2. The Secondary Endpoint Analysis Would be Safety as Measured by the Number of Participants Experiencing Adverse Events and Serious Adverse Events Occurring During 6 Months of Therapy and 1 Month Follow up.(7 months)
- An Additional Secondary Endpoint Analysis Would be Durability of Response Measured Participants CDASI Activity Score or Change in Their CDASI Activity Score at 6 Months Compared to 3 Months.(Data collected at 6 months compared to data collected at 3 months)
- An Additional Secondary Endpoint Analysis Would Assess Quality of Life as Measured at 3 Months Compared to Quality of Life Measured at 6 Months(Data collected at 3 and 6 months after baseline visit)