Preliminary Efficacy and Safety of Apremilast in the Treatment of Acne Conglobata: A Phase II, Single Centre, Open Label, Proof of Concept Study for the Treatment of Acne Conglobata With the PDE-4 Inhibitor Apremilast (APACCO-Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- 50% reduction in number of lesion
研究概览
简要总结
Apremilast mediates its clinical effect through the cAMP-PKA-NFkappaB pathway which results in a clinical picture changes to a decrease of all signs of inflammation.
Due to the NFkappaB mediated chronical inflammation in the pathogenesis of acne conglobata, a treatment with Apremilast seems to be an effective option.
In this study, treatment with Apremilast (Otezla®) will be performed in patients with acne conglobata to observe its preliminary efficacy and safety in an open label, single-centre proof of concept study design.
详细描述
Treatment options for acne conglobata are limited and those which are effective can only be used in short term such as systemic steroids, antibiotics or retinoids due to their association to side effects or potentially teratogenetic effects.
Apremilast, a specific inhibitor for PDE-4, mediates its clinical effect through the cAMP-PKA-NFkappaB pathway which results in a decrease of pro-inflammatory and increase of anti-inflammatory cytokines in several types of leukocytes. The clinical picture changes to a decrease of all signs of inflammation.
Due to the NFkappaB mediated chronical inflammation in the pathogenesis of acne conglobata, a treatment with Apremilast seems to be an effective option.
In this study, treatment with Apremilast (Otezla®) will be performed in patients with acne conglobata to observe its preliminary efficacy and safety in an open label, single-centre proof of concept study design.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of acne conglobata for a minimum of 6 months
- •Active condition of acne conglobata, defined as minimum IGA of 2 (5-point scale) of severity of acne conglobate
- •No clinical significant or severe abnormality of skin (e.g. scars, other severe skin disease) based on medical/medication history or physical examination as determined by the treating physician
- •Number of abscesses ≤ 2
- •Written informed consent obtained from the patients prior to the initiation of any protocol-required procedures
- •Compliance to study procedures and study protocol
- •Age 18 - 65 years
- •patients who do not tolerate or no longer tolerate therapies or for whom the following treatment options are contraindicated:
- •Topical retinoid therapy
- •isotretinoin and/or acitretin as standard therapy
- •Topical treatment with antibiotics, glucocorticoids, retinoids, Vit-D-analogue, calcineurin inhibitors
- •systemic antibiotics, systemic glucocorticoids
- •systemic retinoids
排除标准
- •Previous use of Apremilast, or any other PDE-4 inhibitor
- •According to Summary of Product characteristics (SmPC); see special warnings regarding suicidal ideation and behaviour
- •Known hypersensitivity to any component of the investigator medicinal product (IMP)
- •Current use of strong CYP3A4 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin, and St. John's Wort) Active dermatologic conditions which may confound the diagnosis of acne conglobata or would interfere with the assessment of treatment (e.g., acne inversa, atopic dermatitis, seborrheic dermatitis, ichthyosis, and psoriasis)
- •History of clinically significant infection within the last 4 weeks before screening, which, in the opinion of the treating physician, may compromise the safety of the patient
- •Presentation of special type of acne, including but not limited to:
- •Medication related acne (e.g., steroid abuse)
- •Acne with facial edema
- •Recalcitrant acne
- •Acne cosmetic, pomade acne
- •Acne mechanica
- •Chloracne
- •History of any kind of cancer or carcinoma in situ within the last 5 years before screening
- •History of chronic alcohol/drug abuse within the last 12 months before screening
- •Pregnant or breastfeeding women
- •Females of childbearing potential not willing to use effective contraception (defined as PEARL index <1 - e.g. hormonal contraceptive containing estrogen and progesterone, or progesterone only, applied orally, intravaginal, transdermal or to be injected, IUD) for the duration of the study including also strict abstinence, or partner had a vasectomy
- •Severe kidney insufficiency (glomerular filtration rate (GFR) < 30 ml/min)
- •Any severe disease, which, in the opinion of the treating physician, may interfere or worsen the acne conglobata or could become a safety problem for patients
- •History of or current Hepatitis-B, Hepatitis-C or HIV infection
- •Any active medication which suppresses the immune system, including disease modifying anti-rheumatic drugs (DMARDs) and biologicals
- •Current participation in another investigational clinical trial or participation within 30 days prior to screening
- •Major surgery within the last 4 weeks before screening
- •Subject susceptible to take a local corticosteroid treatment (class I - III) during the study except inhaled or topic when needed to treat a condition outside the treatment area (head, neck, upper trunk)
- •History and current status of suicidal thoughts or behaviour or previous suicidal attempt
- •Washout times for previous therapy for acne conglobata before screening:
- •1 week for any topical treatment (e.g., antibiotics, glucocorticoids, retinoids, Vit-D-analogue, calcineurin inhibitors)
- •4 weeks for any systemic antibiotics, systemic glucocorticoids or UV-therapy
- •12 weeks for any systemic retinoids or any investigational drug
- •Patients who take any kind of contraceptive therapy (eg. estrogen, gestagen) with known positive effect on acne must be on stable dosage for a minimum of 6 month
- •Underage or incapable patients
- •Patients who are legally institutionalized
研究组 & 干预措施
Apremilast
Apremilast twice daily 30 mg
干预措施: Apremilast (Drug)
结局指标
主要结局
50% reduction in number of lesion
时间窗: 24 weeks
proportion of subjects who achieve at least a 50% reduction in total number of inflammatory lesions
次要结局
- Proportionof subjects in Investigator global assessment (IGA)(Baseline to visit 3 (week 2))
- Frequency of adverse events (AEs)(at Follow-up (week 28))
- Seriousness of adverse events (AEs)(at Follow-up (week 28))
- change in itch of the inflammatory lesions measured by a VAS(at visit 7 (week 24))
- proportion of subjects in Investigator global assessment (IGA)(Baseline to visit 7 (week 24))
- change in skin condition(at visit 7 (week 24))
- change in pain of the inflammatory lesions(at visit 7 (week 24))
- change in quality of life(Baseline to visit 7 (week 24))
- change in depression profile(Baseline to Visit 7 (week 24))
- compliance to therapy (drug accountability)(at visit 7 (week 24))
研究者
Dr. Frank Behrens
Sponsor representative
Fraunhofer Institute for Molecular Biology and Applied Ecology