A Randomized, Open-label, Comparative Study to Evaluate an Intermittent Dosing Regimen of Fluticasone Propionate 0.05% Cream (Twice Per Week) in Reducing the Risk of Relapse When Added to Regular Daily Moisturization Using PHYSIOGEL Lotion in Paediatric Subjects With Stabilized Atopic Dermatitis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 107
- 试验地点
- 1
- 主要终点
- Time to the First Relapse of AD During the Maintenance Phase
研究概览
简要总结
This is an open-label, randomized, comparative study, including 4 phases: SCREENING, ACUTE, MAINTENANCE and FOLLOW-UP.
Subjects will complete the SCREENING phase to check the eligibility within 7 days after they sign the written informed consent form. All eligible subjects will be enrolled in ACUTE phase to receive twice daily Fluticasone propionate (FP) 0.05% cream up to 4 weeks. The efficacy and safety in ACUTE phase will be assessed every 2 weeks up to 4 weeks or until Treatment Success which depends on which time point comes first. Then subject can get into the MAINTENANCE phase receiving either emollient twice daily plus FP 0.05% cream once daily twice a week (Group A), or emollient twice daily (Group B), by 1:1 randomization. The treatment duration in MAINTENANCE phase will be up to 20 weeks. The efficacy and safety in MAINTENANCE phase will be assessed every 4 weeks up to 20 weeks or until AD relapse that depends on which time point comes first. If subjects don't experience relapse during MAINTENANCE phase, subsequent FOLLOW-UP phase applying emollient twice daily won't be longer than another 12 weeks.
Total study duration is up to 37 weeks. All subjects receive FP 0.05% cream twice daily up to 4 weeks to all affected sites and any newly occurring sites in ACUTE phase. After randomization in MAINTENANCE phase, subjects either receive emollient twice daily extendedly plus FP 0.05% cream once daily twice a week to all healed sites and any newly occurring sites (Group A), or emollient twice daily extendedly (Group B), up to 20 weeks. In FOLLOW-UP phase, all subjects apply emollient twice daily up to 12 weeks.
This study will enrol 120 subjects, and propose at least 80 subjects to be randomized.
Study Endpoints/Assessments:
Primary endpoint is to observe the median time to the first relapse of AD during MAINTENANCE phase.
Secondary endpoints are:
- Median time to the first relapse of AD during the whole study (including maintenance phase and follow-up phase.
- Numbers of recurrent patients at the end of MAINTENANCE phase;
- Numbers of recurrent patients at the end of FOLLOW-UP phase;
- The effective rates (proportion of "treatment success" patients) during ACUTE phase (V3, W-2±2days;V4, W0±2days )
- Evaluate the safety during the whole study duration (ACUTE phase, MAINTENANCE phase, FOLLOW-UP phase respectively);
- Evaluate visual skin assessment for signs of cutaneous atrophy, epidermal thickening / lichenification and abnormal pigmentation changes during the whole study duration (ACUTE phase, MAINTENANCE phase, FOLLOW-UP phase respectively);
- The change of Quality of Life (QoL) from baseline at the end of MAINTENANCE phase;
- The change of Quality of Life (QoL) from baseline at the end of FOLLOW-UP phase;
- Subjects' post-study evaluation to drugs.
详细描述
Background Atopic dermatitis (AD) is a chronic relapsing skin disease caused by the intervention of plural unspecific stimulation or specific allergens accompanied with cutaneous physiologic dysfunction. AD is one of the most common skin diseases which effects up to 20% of Children and 1-3% of adults in most of countries of the world. The data from a Chinese epidemiologic research shows the prevalence rate of AD is 10.9%in school-age adolescent and 15.3% in preschool children in 2010.
Around 65% patients with AD develop the symptoms in the first year of life; and 90% patients develop the symptoms before 5 years of age. Onset of atopic dermatitis in adolescence or later is uncommon.
The objective of treatment in AD is to relief symptoms and reduces the cutaneous inflammation. Emollients as the mainstay of maintenance therapy are able to restore skin barrier function. Topical glucocorticoids recommended as first line treatment are important anti-inflammatory drugs to be used in AD, especially in the acute phase.
One of the most troublesome features of AD is its chronic relapsing nature suggesting the need for a long-term therapy of this disease. The common long-term treatment of AD is a reactive treatment approach based on the daily application of emollients accompanied by the application of topical glucocorticoids (TCS) or calcineurin inhibitors (TCI) 'as needed'. However, a new alternative treatment 'proactive therapy' has been proven its effective and well-tolerated to reduce AD relapse in clinical trials and recommended by guidelines.
This proactive therapy starts with an intensive topical anti-inflammatory therapy until all lesions have virtually cleared, followed by long-term, low-dose intermittent application of anti-inflammatory drugs to previous affected and now clinically healthy-looking skin combined with daily application of emollients to always unaffected areas.
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
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the GSK investigational product or other study treatment that may impact subject eligibility is provided in the package insert of CUTIVATE and PHYSIOGEL Lotion.
- •Deviations from inclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential. Subjects eligible for enrolment in the study must meet all of the following criteria:
- •male or female patients age between 1 to 18 years old (including 1 year and excluding 18 years old);
- •Diagnose atopic dermatitis according to criteria of Williams;
- •Mild to moderate AD on the head/neck, trunk, upper limbs or lower limbs and PSGA scores 2-3;
- •The informed consent must be signed before any study specific tests or procedures are initiated;
- •Subjects eligible for enrolment in the MAINTENANCE phase of the study must meet all of the following criteria:
- •Achieve treatment success after receiving Fluticasone propionate 0.05% cream twice daily up to 4 weeks in ACUTE phase
排除标准
- •Deviations from exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
- •Subjects meeting any of the following criteria must not be enrolled in the study:
- •Acute phase:
- •Dermatitis of only the face, feet or hands;
- •The involved area has exceeded 10% of the whole body area;
- •Diagnosed contact dermatitis at predilection sites of AD;
- •Atrophy, telangiectasia, extensive scarring lesions in the area or areas to be treated;
- •Had topical therapies including but not limit to calcineurin inhibitors (topical tacrolimus or topical pimecrolimus), corticosteroids, antihistamines within 14 days prior to screening;
- •Has accepted nonsteroidal immunosuppressants (eg cyclosporine, methotrexate), or ultraviolet light treatments including ultraviolet-A and ultraviolet-B, or systemic corticosteroids regardless administration by oral, intramuscular, or intravenous within 4 weeks prior to screening;
- •Pregnant or breast-feeding. Women of Childbearing Potential (WOCBP) with a positive urine pregnancy test performed within 7 days before the start of treatment;
- •Has immunocompromised disease (e.g. lymphoma, AIDS, Wiskott-Aldrich syndrome) or have a history of malignancy (including basal cell carcinoma, squamous cell carcinoma, melanoma);
- •Has open skin infections (bacterial, viral or fungal) if at the application site;
- •Has head lice or scabies;
- •Present with clinical conditions other than AD that may interfere with the valuation (e.g. generalized erythrodema, toxicoderma, acne, Netherton's Syndrome, psoriasis);
- •Require systemic therapy for the treatment of atopic dermatitis, or had systemic therapy including but not limit to antihistamines within 14 days prior to screening;
- •Has accepted any experimental or investigational drug or therapy within 6 weeks prior to screening;
- •Has known hypersensitivity to Fluticasone Propionate 0.05% cream, or PHYSIOGEL lotion, or relate drugs;
- •Non-compliance with general medical treatment, or are known to miss appointments, or don't intend to comply with the protocol for the duration of the study;
- •Drug abuse, mental dysfunction, or other factors limiting the subject's ability to cooperate fully with study-related procedures;
- •Know to be unreliable or may be unable to complete the study;
- •Any condition or prior/present treatment that would render the subject not eligible for the study;
- •Maintenance phase:
- •Accepted topic therapies other than Fluticasone propionate 0.05% cream and emollients during the ACUTE phase;
- •Has active skin infection (bacterial, viral or fungal).
研究组 & 干预措施
fluticasone propionate
To evaluate an intermittent dosing regimen of fluticasone propionate 0.05% cream (twice per week) in reducing the risk of relapse when added to regular daily moisturization using PHYSIOGEL Lotion in paediatric subjects with stabilized atopic dermatitis
干预措施: Fluticasone propionate (Drug)
physiogel
To compare the efficacy and safety of fluticasone propionate 0.05% cream (twice per week) added to regular daily moisturization using Physiogel Lotion with Physiogel Lotion alone in paediatric subjects with stabilized atopic dermatitis
干预措施: Fluticasone propionate (Drug)
结局指标
主要结局
Time to the First Relapse of AD During the Maintenance Phase
时间窗: From the start of treatment up to Week 20 during the Maintenance Phase
Time to the first relapse of AD is defined as the number of days from start of the FP treatment in Maintenance Phase until AD relapse. AD relapse is defined as participants with PSGA exacerbation score \>=2 (the six-point scale of PSGA score range from 0 to 5 where 0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe, 5=very severe) compared to PSGA score of treatment success during Acute Phase. Participants with treatment success are defined as participants with PSGA \<=1; and the improvement \>=2 compared to Baseline.
次要结局
- Numbers of Recurrent Participants at the End of the Maintenance Phase (Week 20)(From Week 0 (or treatment success, if earlier) to Week 20)
- Change From Baseline in Cutaneous Atrophy Sign Score, Epidermal Thickening /Lichenification Sign Score and Abnormal Pigmentation Score Using Visual Analogue Scale (VAS) at the End of the Acute Phase(From the start of treatment up to Visit 4 (Week 0) or treatment success (depends on which time point comes first))
- Number of Participants With Post-study Assessment of Skin Emollients Using Questionnaire(At early withdrawal or end of the therapy visit (up to Week 32))
- Median Time to the First Relapse of AD During the Maintenance Phase and Follow-up Phase(From the start of treatment up to Week 32 during the Maintenance Phase and Follow-up Phase)
- Numbers of Recurrent Participants at the End of the Follow-up Phase (Week 32)(From Week 20 to Week 32)
- Change From Baseline in Quality of Life (QoL) at the End of the Maintenance Phase(Baseline and Week 20)
- Change From Baseline in Cutaneous Atrophy Sign Score, Epidermal Thickening /Lichenification Sign Score and Abnormal Pigmentation Score Using Visual Analogue Scale (VAS) at the End of the Maintenance Phase and Follow-up Phase(Baseline, Week 20 and Week 32)
- Number of Participants With "Treatment Success" During the Acute Phase(From the start of treatment up to Visit 4 (Week 0) or treatment success (depends on which time point comes first))
- Change From Baseline in QoL at the End of the Follow-up Phase(Baseline and Week 32)
- Number of Participants With Post-study Assessment of Lotion Qualities (1) Using Questionnaire(At early withdrawal or end of the therapy visit (up to Week 32))
- Number of Participants With Post-study Assessment of Lotion Qualities (2) Using Questionnaire(At early withdrawal or end of the therapy visit (up to Week 32))