Efficacy of Oral Alitretinoin Treatment in Patients With Palmo-plantar Pustulosis (PPP) Inadequately Responding to Standard Topical Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Number of Participants With PPPASI 50 Response and PPPASI 75 Response
研究概览
简要总结
The main purpose of this study is to demonstrate the improvement in the skin condition rate of patients receiving alitretinoin compared to patients receiving placebo.
详细描述
Palmo-plantar pustulosis (PPP) is an inflammatory skin disease affecting palms and soles. The disease is considered as a sub-form of psoriasis and presents with sterile pustules of the palms and the soles. This study investigates the efficacy of alitretinoin in patients who have not responded to topical drugs (e.g., steroid creams), who are suffering for at least 6 month from the condition and whose disease severity is confirmed by a score.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A female subject is eligible to participate if she is of:
- •Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea and a follicle stimulating hormone concentration of ≥40 international units (IU)/L.
- •Child-bearing potential with negative pregnancy test as determined by human chorionic gonadotropin (hCG) test at screening or prior to dosing and either 1) agrees to use a medically acceptable contraception method for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point and continue contraception until the end of the study, or 2) has only same-sex partners, when this is her preferred and usual lifestyle.
- •Capable of understanding and willing to provide signed and dated written voluntary informed consent (and any local or national authorization requirements) before any protocol specific procedures are performed.
- •Male or female aged at least 18 years at time of consent and at time of first dose.
- •Have PPP for at least 6 months, with or without psoriasis lesions on other areas of the skin
- •A PPPASI score of at least 8 with involvement of at least 10% of the palms and/or the soles
- •Refractory to standard topical corticosteroid therapy
排除标准
- •Unable to comply with the requirement of the study
- •Female subjects who are pregnant or who plan to become pregnant or who are breast feeding
- •Subjects whose disease is adequately controlled by standard non-medicated therapy (skin moisturizing and protection)
- •Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component, especially soybean oil and partly hydrogenated soybean oil
- •Treated with any of the following treatments 4 weeks before the start of study treatment:
- •systemic drugs: corticosteroids, immunosuppressants, methotrexate
- •phototherapy: ultraviolet B light therapy [UVB], psoralen with ultraviolet A combination therapy [PUVA], Grenz rays, X-rays
- •Treated with biologic treatments within 6 weeks prior to start of study treatment.
- •Abnormal hematology
- •Treated with any systemic or topical retinoids within 3 months or 1 month, respectively, before start of study treatment
- •Treated with high-potency topical corticosteroids within 2 weeks before the start of study treatment
- •Severe generalized pustular psoriasis
- •A skin condition of palms and/or soles that interferes with the diagnosis of PPP by the investigator
- •Any condition that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study.
- •Hepatic insufficiency, severe renal failure, uncontrolled hypercholesterolemia as characterized by:
- •AST/ ALT >2.5 x upper limit of normal (ULN)
- •Creatinine clearance <60 mL/min (calculated, Cockcroft-Gault)
- •Fasting triglyceridemia >1.5 x upper limit of normal (ULN)
- •Fasting cholesterol >1.5 x ULN
- •Fasting low-density lipoprotein (LDL) cholesterol >1.5x ULN
- •Subjects with hypothyroidism as indicated by thyroid stimulating hormone (TSH) above ULN and thyroxine (T4) test below LLN or hypervitaminosis A
- •Subjects with unstable cardiac disease or poorly controlled cardiovascular risk factors, for example:
- •Acute coronary syndrome or coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass graft [CABG]) within 3 months before start of study treatment
- •Poorly controlled diabetes mellitus (HbA1c >8.5%)
- •Systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg at the screening examination
- •Subjects receiving drugs with a potential for drug-drug interaction, such as systemic tetracyclines, ketoconazole, or St. John's Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before start of study treatment
- •Subjects included in the study of an investigational drug within 2 months before start of study treatment (3 months for biologics)
- •Subjects with a score of 20 or more on the Center for Epidemiologic Studies Depression scale (CES-D), or with active major psychiatric disorder (eg, Major Depressive Disorder, Generalized Anxiety Disorder, Bipolar Disorder [I or II], or schizophrenia)
- •Subjects who score a 4 or 5 for the previous 30 days on the Columbia Suicide Severity Rating Scale (CSSRS) at Screening or Baseline
- •Subjects who have made a suicide attempt within the 6 months preceding the Screening or Baseline visits
研究组 & 干预措施
Active
to receive study drug (alitretinoin, 20 patients)
干预措施: alitretinoin (Drug)
Placebo
to receive placebo (dummy drug, 10 patients)
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With PPPASI 50 Response and PPPASI 75 Response
时间窗: From Baseline until EOT (Week 24) or the last assessment
The investigator evaluated the PPPASI score on a 5-point scale. The parameters of erythema, total number of pustules, and desquamation were scored for the right/left palm and the right/left sole. After correcting the scores for area (based on a 7-point scale) and the site involved (palm or sole), the PPPASI score per palm/sole was produced. The final PPPASI score was calculated as the sum of the PPPASI score for the right sole + the PPPASI score for the left sole + the PPPASI score for the right palm + the PPPASI score for the left palm and ranges from 0 (no palmo-plantar pustulosis psoriasis \[PPP\]) to 72 (most severe PPP). Change from Baseline is defined as value at the EOT minus the Baseline value. PPPASI 50 response and PPPASI 75 response are defined as a 50% and 75% decrease, respectively, in the PPPASI score from Baseline.
Change From Baseline in the Palmo-plantar Pustulosis Psoriasis Area and Severity Index (PPPASI) Score at the End of Treatment (EOT) (Week 24) or at the Last Assessment
时间窗: Baseline and EOT (Week 24) or the last assessment
The investigator evaluated the PPPASI score on a 5-point scale. The parameters of erythema, total number of pustules, and desquamation were scored for the right/left palm and the right/left sole. After correcting the scores for area (based on a 7-point scale) and the site involved (palm or sole), the PPPASI score per palm/sole was produced. The final PPPASI score was calculated as the sum of the PPPASI score for the right sole + the PPPASI score for the left sole + the PPPASI score for the right palm + the PPPASI score for the left palm and ranges from 0 (no palmo-plantar pustulosis psoriasis \[PPP\]) to 72 (most severe PPP). Change from Baseline is defined as value at the EOT minus the Baseline value.
次要结局
- Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) and an AE/SAE Related to Study Treatment(From Baseline until safety follow up (Week 29))
- Total Pustule Count at Baseline; Weeks 4, 8, 12, 16, and 20; and at EOT (Week 24)(Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24))
- Absolute Change From Baseline in Fasted Lipid Laboratory Test Values at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and at Safety Follow-up (Week 29)(Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29))
- Absolute Change From Baseline in Fasted LDL/HDL Ratio at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and at Safety Follow-up (Week 29)(Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24) and safety follow-up (Week 29))
- Absolute Change From Baseline (BL) in Total Pustule Count at Weeks 4, 8, 12, 16, and 20 and at EOT (Week 24)(Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24))
- Mean Nail Psoriasis Severity Index (NAPSI) Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Baseline, Week 12, and EOT (Week 24)(Baseline, Week 12, and EOT (Week 24))
- Mean Center for Epidemiological Studies Depression Scale (CES-D) Scores at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)(Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29))
- Absolute Change From Baseline (BL) in CES-D Scores at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)(Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29))
- Mean Modified Psoriasis Area Severity Index (mPASI) Score at Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24)(Baseline; Weeks 4, 8, 12, 16, and 20; and EOT (Week 24))
- Change From Baseline in the mPASI Score at EOT (Week 24) or at the Last Assessment(Baseline and EOT (Week 24) or the last assessment)
- Number of Participants With mPASI 50 Response and mPASI 75 Response(From Baseline until EOT (Week 24))
- Absolute Change From Baseline in NAPSI Score for Nail Bed Psoriasis and Nail Matrix Psoriasis at Week 12, and EOT (Week 24)(Baseline, Week 12, and EOT (Week 24))
- Number of Participants With the Indicated Shift in the Indicated Laboratory Values From Baseline (BL) to EOT (Week 24)(From Baseline until EOT (Week 24))
- Mean Columbia Suicide Severity Rating Scale (CSSRS) Scores at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)(Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24), and safety follow-up (Week 29))
- Absolute Change From Baseline in the CSSRS Score at Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)(Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and safety follow-up (Week 29))
- Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Screening, Baseline, and EOT (Week 24)(Screening, Baseline, and EOT (Week 24))
- Mean Heart Rate (HR) at Baseline, Screening, and EOT (Week 24)(Screening, Baseline, and EOT (Week 24))
- Mean Body Weight at Screening, Baseline ,and EOT (Week 24)(Screening, Baseline, and EOT (Week 24))
- Change From Baseline in SBP and DBP at EOT (Week 24)(Baseline and EOT (Week 24))
- Change From Baseline in Heart Rate at EOT (Week 24)(Baseline and EOT (Week 24))
- Change From Baseline in Weight at EOT (Week 24)(Baseline and EOT (Week 24))
- Number of Participants With Normal/Abnormal Physical Status at Baseline With a Worst Post-Baseline Finding of Normal/Abnormal(Baseline and EOT (Week 24))
- Number of Participants With a Negative Serum Pregnancy Test at Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); and Safety Follow-up (Week 29)(Screening; Baseline; Weeks 4, 8, 12, 16, and 20; EOT (Week 24); safety follow-up (Week 29))