A Double-blind, Randomized, Placebo-controlled Phase III Trial to Investigate the Efficacy and Safety of NPC-12G Gel (Topical Formulation of Sirolimus) to Angiofibroma and Other Skin Lesions in Patients With Tuberous Sclerosis Complex
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Improvements in angiofibroma
研究概览
简要总结
The purpose of this trial is to evaluate the efficacy and safety of NPC-12G gel (topical formulation of sirolimus) versus placebo gel to facial angiofibroma and other skin lesions in patients with tuberous sclerosis complex (TSC)
详细描述
Tuberous Sclerosis Complex (TSC) is an autosomal dominant hereditary disease that causes benign tumors on the almost whole body (including skin, brain, kidney, lung and heart), behavior disorder as autism, mental retardation and neurologic symptom as epilepsy. Angiofibroma is TSC-specific facial skin lesions, and hamartoma caused by increase of the component of skin connective tissues and blood vessels. Other skin lesions due to TSC are white macule(hypomelanotic macule), plaque, shagreen patch and ungual fibromas. Current therapeutic methods for angiofibroma are laser or surgical treatments, but there are problems as many relapses, deficiency of evidence, change of pigment, scar and risk of infection.
This will be a multicenter, double-blind, randomized, placebo-controlled parallel group trial. The trial has three phases; the screening phase, double-blinded treatment phase, and post-treatment phase. The screening phase comprises a screening visit where subject's initial eligibility will be evaluated. During double-blinded treatment phase, patients who meet all entry criteria for the trial will be randomized into two groups, and they will apply 0.2% NPC-12G gel or placebo gel topically twice a day for 12 weeks.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 3 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients 3 years old or greater at the time of informed consent
- •Patients who are diagnosed as definite diagnosis according to diagnostic criteria for tuberous sclerosis complex (International Tuberous Sclerosis Complex Consensus Conference 2012)
- •Patients with three or more papules of angiofibroma ( >= 2 mm in diameter with redness in each) on the face at screening tests
- •Patients who are not suitable for therapy with laser or surgery, or who do not want therapy with laser or surgery
- •Patients or his/her guardian who give a written informed consent in understanding and willingness after having received enough explanation of the test drug and the current trial plan
排除标准
- •Patients who are hard to apply the test drug topically with keeping compliance
- •Patients with clinical findings such as erosion, ulcer and eruption on or around the lesion of angiofibroma, which may affect assessment of safety or efficacy
- •Patients who are hard to be taken pictures of their lesions adequately in such cases that they may not follow instruction of stillness
- •Patients with a history of hypersensitivity to alcohol or allergy to sirolimus
- •Patients who have complications such as malignant tumor, infection, serious heart disease, hepatic function disorder, renal function disorder or blood disorders which severity are considered by investigator as grade 2 or more severe with reference to ''Concerning classification criteria for seriousness of adverse drug reactions of medical agents''
- •Patients who have complications such as diseases unsuitable for the trial participation, for examples, uncontrolled diabetes (fasting blood glucose level >140 mg/dL or postprandial blood glucose level > 200 mg/dL), dyslipidemia (cholesterol level > 300 mg/dL or > 7.75 mmol/L, triglycerides level > 300 mg/dL or > 3.42 mmol/L), etc.
- •Patients who have taken drugs with mTOR inhibitory action including sirolimus, everolimus or temsirolimus within 12 months before the initial registration
- •Patients who have applied topical tacrolimus on the lesion of angiofibroma within 3 months before the initial registration
- •Patients who have received therapy with laser or surgery to the lesion of angiofibroma within 6 months before the initial registration
- •Female patients who may be pregnancy or are lactating
- •Patients who cannot agree to take appropriate measures of contraception until completion of post-treatment phase or follow-up period after discontinuation from informed consent
- •Patients who have participated in other clinical trial and have taken a trial drug within 6 months before the initial registration
- •Others, patients who are considered by the investigator as unsuitable for participation in the trial
研究组 & 干预措施
NPC-12G gel
NPC-12G gel is containing 0.2% Sirolimus
干预措施: NPC-12G gel (Drug)
Placebo gel
Placebo gel is matched ingredient with NPC-12G gel
干预措施: Placebo gel (Drug)
结局指标
主要结局
Improvements in angiofibroma
时间窗: 12 weeks
Improvements comparing with baseline is assessed using photograph by the central photo-judgement committee
次要结局
- Improvements in redness of angiofibroma(Week 4, 8, 12 and follow-up Week 16)
- Improvements in hypomelanotic macule and plaque of upper neck(Week 4, 8, 12 and follow-up Week 16)
- The rate of patients who are evaluated as ''improvement'' or more (improvement rate) in primary outcome measure and in secondary outcome measures above outcome 1 to 5(Week 4, 8, 12 and follow-up Week 16)
- Change in total score from baseline for DLQI and CDLQI(Week 4, 8, 12 and follow-up Week 16)
- Adverse events(16 weeks)
- Laboratory findings(16 weeks)
- Serious adverse events(16 weeks)
- Vital sign(16 weeks)
- Sirolimus blood concentration(Baseline, Week 4 and Week 12)
- Improvements in angiofibroma(Week 4, 8, 12 and follow-up Week 16)