A Randomized (1:1), Double-blind, Parallel, Placebo-controlled Exploratory Pilot Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Systemic (po) Application of MP1032 in Patients With Moderate to Severe Chronic Plaque Psoriasis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 4
- 主要终点
- Safety - Treatment Emergent Adverse Events (TEAEs) - Number of TEAEs
研究概览
简要总结
This Phase IIa study is designed to assess the safety, tolerability and pharmacokinetics of oral MP1032 in patients with moderate to severe psoriasis over a period of 6 weeks. Secondary endpoints to evaluate clinical parameters for psoriasis during the 6 week treatment period and a 4-week follow up will provide an opportunity to perform a first assessment of oral MP1032's clinical efficacy in the treatment of moderate to severe psoriasis.
The study population will consist of 44 enrolled (40 completed) patients with moderate to severe chronic plaque psoriasis. Patients must be able to provide written consent and meet all the inclusion criteria and none of the exclusion criteria.
详细描述
This study is a randomized, double-blind, parallel, placebo-controlled exploratory pilot study to evaluate safety, pharmacokinetics and efficacy of systemic oral (po) administration of 100 mg MP1032 bid in adult patients with moderate to severe chronic plaque psoriasis.
The study design consists of a 28-day screening/run-in period, a 42-day treatment period, 1 day for the End of Treatment visit, and a 28-day follow-up period. Forty-four patients who meet the entry criteria will be randomized on Day 1 in a 1:1 ratio to receive either 100 mg MP1032 or placebo orally twice daily for 42 days. The goal is to have 40 patients (20 in each treatment group) complete the study.
Pharmacokinetic sampling will occur on 3 designated study days. Safety will be monitored from the signing of the informed consent form (ICF) until the last follow-up visit on Day 71.
Efficacy will be assessed on 6 designated study days using the following assessments: PASI, PGA, DLQI, mNAPSI, and EQ-5D 5L (VAS).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants legally competent to sign and give informed consent.
- •Adult male and female patients aged 18 to 65 years with chronic plaque psoriasis:
- •PASI score > 10 at screening and
- •Disease duration of ≥ 6 months at the initiation of study medication.
- •Body Mass Index (BMI) between 18.5 and 34.9 kg/m
- •Diagnosis of chronic plaque psoriasis confirmed by a dermatologist/physician.
- •Women of childbearing potential (WCBP) must have a negative urine pregnancy test at Screening (Visit 1). In addition, sexually active WCBP must agree to use 2 forms of adequate contraception throughout the trial.
- •Post-menopausal women with spontaneous amenorrhea for at least 12 months and serum levels follicle stimulating hormone (FSH) Levels indicating post-menopausal state as per local laboratory reference ranges. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study. Sterilized women may be included.
- •Patients must meet the following clinical laboratory criteria:
- •White blood cell count ≥ 3.5 x 10^9/L
- •Platelet count ≥ 100 x 10^9/L
- •Serum creatinine ≤ 1.5 x upper limit of normal (ULN); estimated glomerular filtration rate > 60 mL/min
- •Total bilirubin ≤ 1.5 x ULN
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 1.5 x ULN
- •Hemoglobin ≥ lower limit of normal as per local laboratory reference ranges for women and men accordingly
- •No coagulopathy (International Normalized Ratio [INR] < 1.5).
- •Patients agree not to increase normal sun exposure during the course of the study.
- •Patients are able to swallow 2 small capsules during each administration.
- •Patients are considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, or medication intake according to the judgment of the Investigator.
排除标准
- •Patients with non-plaque form of psoriasis (erythrodermic, guttate, pustular or palmo plantar psoriasis; severe form of psoriasis arthritis, inverse form of psoriasis). Mild to moderate cases of psoriasis arthritis are allowed provided there is no impact on study objectives as determined by the Investigator.
- •Patients with drug-induced psoriasis.
- •Evidence of skin conditions at the time of screening visit other than psoriasis that would interfere with evaluations of the effect of study medication on psoriasis.
- •Patients with any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form.
- •Pregnant or lactating females or females planning to become pregnant during the study and/or within 28 days following the last dose of study medication.
- •Male patients planning a partner pregnancy or sperm donation during the study or within 3 months following the last dose of study medication.
- •Known allergies to mannitol, macrophage modulators, and gelatin.
- •Patients with a recent history or current signs or symptoms, as determined by the Investigator, of severe, progressive viral or bacterial infections, of clinically significant cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic insufficiency disease (excluding psoriasis) requiring systemic treatment or other major diseases, which are not well controlled and may interfere with the conduct of the trial.
- •Patients with active malignancy or history of malignancy, except for basal cell or squamous cell carcinoma and actinic keratosis. Basal cell carcinoma and small squamous cell carcinoma of the skin which have been excised according to guidelines within the last 5 years or in situ cervical carcinoma that has been fully treated and shows no evidence of recurrence are allowed.
- •Clinically significant abnormality on 12-lead electrocardiogram (ECG) at screening.
- •Positive human immunodeficiency virus (HIV), hepatitis B or hepatitis C laboratory result.
- •Previous strong sun exposure (eg, sea holiday) within the 28 days before study medication initiation.
- •Known photo allergy and/or experienced drug-induced photo toxicity.
- •Elective (planned) hospitalization or medical intervention preventing patient from following the protocol requirements.
- •Prior Treatment: Drug class >> Last dose prior to study medication initiation (washout period)
- •Topical psoriasis medications (including, but not limited to corticosteroids, calcipotriene, topical vitamin D derivates, retinoids, coal tar) >> 14 days
- •Topical immunosuppressive drugs (tacrolimus, pimecrolimus, or anthralin) >> 14 days (Exception: Non-medicated emollients, moisturizers and sunscreens will be allowed), Use of low potency topical steroids for critical areas such as the face, genitalia, and scalp may be allowed until 24 hours prior to randomization.
- •Systemic treatment (non-biologic): Systemic immunosuppressant agents (eg: methotrexate, cyclosporine, azathioprine), Systemic fumarate, Systemic corticosteroids >> 28 days
- •Phototherapy or photochemotherapy/photosensitizing drugs >> 28 days
- •Systemic retinoids >> 12 weeks
- •Any investigational drug >> 24 weeks (systemic); 4 weeks (topical)
- •Any Anti-TNFs: Infliximab, adalimumab, golimumab, etanercept, etc. >> 12 weeks
- •Other Biologics and other systemic therapies: ustekinumab, alefacept, apremilast, Efalizumab, certolizumab pegol, secukinumab, etc. >> 24 weeks
- •Rituximab >> 12 months
- •Drinking or ingesting grapefruit, pomegranate, grapefruit juice or grapefruit containing products within 14 days of study medication initiation.
- •Planned use of any ultraviolet (UV) phototherapy or photochemotherapy/photosensitizing drugs during the course of the study and within 28 days following the last dose of the study medication.
- •Patients with a history of chronic alcohol or drug abuse within 6 months of study medication initiation.
- •Patients employed by MetrioPharm or a contract research organization (CRO) involved in the clinical study.
- •Vulnerable patients (eg, patients kept in detention).
- •Patients who are unable to communicate, read and understand the local language, or who display any other condition, which, in the Investigator's opinion, makes them unsuitable for clinical study participation.
研究组 & 干预措施
MP1032
Test Product:
100 mg MP1032 (= 2 capsules a 50 mg) are provided orally twice daily for 42 days
干预措施: MP1032 (Drug)
Placebo
Placebo to MP1032:
2 capsules of Placebo are provided orally twice daily for 42 days
干预措施: Placebo (Drug)
结局指标
主要结局
Safety - Treatment Emergent Adverse Events (TEAEs) - Number of TEAEs
时间窗: Continuously from Treatment Start until the last follow-up visit on Study Day 71
Number of TEAEs (Treatment Emergent Adverse Events) occured was determined by treatment group. Furthermore, the absolute and relative frequencies for patients with a given AE, as well as the number of events of the individual AEs that have occurred throughout the study (inclusive screening), were determined within each treatment group and system organ class. Results thereto are provided in the section "Reported Adverse Events". AEs are collected throughout the study. Abnormal values received from Clinical Laboratory Safety Testing (hematology, biochemistry and urinalysis on Study Days 1, 15, 29, 43, 57 and 71), Vital Signs (Systolic blood pressure, diastolic blood pressure, heart rate, tympanic body temperature and respiration rate on Study Days 1, 15, 29, 43, 57 and 71), ECG (Study Days 1, 43 and 71) and Physical Examination (Study Days 1, 43 and 71) were also handled as AE.
Safety - Treatment Emergent Adverse Events (TEAEs) - Number of Related TEAEs by SOC
时间窗: Continuously from Treatment Start until the last follow-up visit on Study Day 71
Number of related TEAEs (Treatment Emergent Adverse Events) occured by SOC (System Organ class) was determined by treatment group. Furthermore, the absolute and relative frequencies for patients with a given AE, as well as the number of events of the individual AEs that have occurred throughout the study (inclusive screening), were determined within each treatment group and system organ class. Results thereto are provided in the section "Reported Adverse Events". AEs are collected throughout the study. Abnormal values received from Clinical Laboratory Safety Testing (hematology, biochemistry and urinalysis on Study Days 1, 15, 29, 43, 57 and 71), Vital Signs (Systolic blood pressure, diastolic blood pressure, heart rate, tympanic body temperature and respiration rate on Study Days 1, 15, 29, 43, 57 and 71), ECG (Study Days 1, 43 and 71) and Physical Examination (Study Days 1, 43 and 71) were also handled as AE.
Safety - Treatment Emergent Adverse Events (TEAEs) - Number of Patients With TEAEs
时间窗: Continuously from Treatment Start until the last follow-up visit on Study Day 71
Number of patients with TEAEs (Treatment Emergent Adverse Events) was determined by treatment group. Furthermore, the absolute and relative frequencies for patients with a given AE, as well as the number of events of the individual AEs that have occurred throughout the study (inclusive screening), were determined within each treatment group and system organ class. Results thereto are provided in the section "Reported Adverse Events". AEs are collected throughout the study. Abnormal values received from Clinical Laboratory Safety Testing (hematology, biochemistry and urinalysis on Study Days 1, 15, 29, 43, 57 and 71), Vital Signs (Systolic blood pressure, diastolic blood pressure, heart rate, tympanic body temperature and respiration rate on Study Days 1, 15, 29, 43, 57 and 71), ECG (Study Days 1, 43 and 71) and Physical Examination (Study Days 1, 43 and 71) were also handled as AE.
Safety - Treatment Emergent Adverse Events (TEAEs) - Number of Patients With Related TEAEs by SOC
时间窗: Continuously from Treatment Start until the last follow-up visit on Study Day 71
Number of patients with related TEAEs (Treatment Emergent Adverse Events) occured by SOC (System Organ class) was determined by treatment group. Furthermore, the absolute and relative frequencies for patients with a given AE, as well as the number of events of the individual AEs that have occurred throughout the study (inclusive screening), were determined within each treatment group and system organ class. Results thereto are provided in the section "Reported Adverse Events". AEs are collected throughout the study. Abnormal values received from Clinical Laboratory Safety Testing (hematology, biochemistry and urinalysis on Study Days 1, 15, 29, 43, 57 and 71), Vital Signs (Systolic blood pressure, diastolic blood pressure, heart rate, tympanic body temperature and respiration rate on Study Days 1, 15, 29, 43, 57 and 71), ECG (Study Days 1, 43 and 71) and Physical Examination (Study Days 1, 43 and 71) were also handled as AE.
Pharmacokinetics (PK) - Plasma Concentrations
时间窗: Study Days 1, 15, 29 and 43
Study Day 1 - sampling 15 minutes, 30 minutes, 1 hour and 2 hours postdose Study Days 15, 29 and 43 - only one sample was taken any time postdose (time of the last dose was recorded). No statistical Evaluation has been performed.
Pharmacokinetics (PK) - Maximum Observed Concentration (Cmax)
时间窗: Study Day 1
Maximum observed plasma concentration (Cmax)as observed on Day 1 with sampling times of 15 minutes, 30 minutes, 1 hour, and 2 hours postdose
Pharmacokinetics (PK) - Time
时间窗: Study Day 1
Sampling 15 minutes, 30 minutes, 1 hour, and 2 hours postdose t max = Time corresponding to occurence of Cmax t last = Time of last quantifiable concentration
Pharmacokinetics (PK) - Area Under the Curve (AUC)
时间窗: Study Day 1
AUC (lin-log) - Sampling 15 minutes, 30 minutes, 1 hour, and 2 hours postdose AUC 2h = area under the plasma concentration-time curve from time zero to 2 hours AUC t = area under the plasma concentration-time curve from time zero to the last quantifiable concentration.
Pharmacokinetics (PK) - Area Under the Curve (AUC) - Subgroups
时间窗: Study Day 1
AUC (lin-log) - Sampling 15 minutes, 30 minutes, 1 hour, and 2 hours postdose AUC 2h = area under the plasma concentration-time curve from time zero to 2 hours AUC t = area under the plasma concentration-time curve from time zero to the last quantifiable concentration.
次要结局
- Psoriasis Area Severity Index (PASI) - Observed PASI Values(Study Day 1, 43, 57 and 71)
- Psoriasis Area Severity Index (PASI) - Change From Baseline(Study Day 1 and 43)
- Psoriasis Area Severity Index (PASI) - PASI Percentage Change - Including Subgroup Analysis AUC2h(Study Day 1, 29 and 43)
- Psoriasis Area Severity Index (PASI) - PASI Percentage Change - Including Subgroup Analysis AUCt(Study Day 1, 29 and 43)
- Psoriasis Area Severity Index (PASI) - PASI 30 and PASI 50 - Number of Patients(Study Day 1, 29 and 43)
- Psoriasis Area Severity Index (PASI) - PASI 30 and PASI 50 - Responder Frequency(Study Day 1, 29 and 43)
- Physician's Global Assessment (PGA) - Observed Values and Change From Baseline(Study Day 1 and 43)
- Dermatology Life Quality Index (DLQI) - Observed Values and Change From Baseline.(Study Day 1 and 43)
- EQ-5D 5L Visual Analogue Scale (VAS)(Study Day 1 and 43)
- Modified Nail Psoriasis Severity Index (mNAPSI) - Observed Values and Change From Baseline(Study Day 1 and 43)