NCT02474069已完成3 期
A Randomized, Double-blind, Multicenter Study to Assess the Efficacy and Safety of 16 Weeks Secukinumab Dosage Interval Shortening in Comparison to Continued Standard Treatment (4-weekly 300 mg s.c.) in Patients With Moderate-severe Plaque Type Psoriasis Who Achieved Less Than Almost Clear Skin After 16 Weeks Under the Standard Dose of Secukinumab
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 772
- 试验地点
- 1
- 主要终点
- Number of Participants With PASI 90 Response at Week 32 for PPS
研究概览
简要总结
This study is designed to support the optimal use of secukinumab by providing data to refine guidance on dosing flexibility in patients with psoriasis. The purpose of the study is to explore the effects of dosage interval shorteng to achieve PASI 90 at week 32 for patients who had less than almost clear skin at week 16.
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
- Double (Participant, Investigator)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects eligible for inclusion in this study must fulfill all of the following criteria:
- •Subjects must be able to understand and communicate with the investigator and must give a written, signed and dated informed consent before any study related activity is performed and who are willing and capable to comply with all study procedures.
- •Men or women at least 18 years of age at time of screening.
- •Chronic plaque type psoriasis diagnosed for at least 6 months prior to baseline
- •Moderate to severe plaque type psoriasis at baseline derived from the European consensus (Mrowietz et al., 2011): BSA (Body Surface Area) >10% and PASI>10 and DLQI>
- •Candidates for biologic therapy who failed to respond to, or who had a contraindication to or were intolerant to previous conventional systemic therapies.
- •According to local guidelines, to exclude chest infection before initiation of a biologic immunomodulating therapy, it is necessary to have obtained an image of the chest (X-ray, computerized tomography or magnetic resonance imaging) within 12 weeks prior to screening and have this evaluated by a qualified physician.
排除标准
- •Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttata psoriasis).
- •Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium).
- •Ongoing use of prohibited psoriasis and non-psoriasis treatments. Washout periods have to be adhered to.
- •Subjects not willing to limit UV light exposure (e.g., sunbathing and/or the use of tanning devices) during the course of the study.
- •Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.
- •Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting IL-17A or the IL-17A receptor (e.g. brodalumab, ixekizumab).
- •History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.
- •Study personnel or first degree relatives of investigator(s) must not be included in the study.
- •Women who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index <1**) during and up to at least 4 weeks after the end of treatment. A negative pregnancy test (serum) for all women and for girls entering menarche is required with sufficient lead time before inclusion
- •*definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m or 6 weeks post- surgical bilateral oophorectomy with or without hysterectomy
- •**examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynakologie und Geburtshilfe:
- •hormonal oral contraception (Combination of estrogen and gestagen, PI=0.1-0.9) hormonal vaginal ring (combination of estrogen and gestagen, PI=0.65 uncorr.; 0.4 corr.)
- •hormonal transdermal patch (combination of estrogen and gestagen, PI= 0.72 uncorr.; 0.9 corr.)
- •Estrogen-free ovulation inhibitors containing desogestrel (PI=0.14)
- •Implanted hormones containing etonogestrel (PI=0-0.08)
- •Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.)
- •Intra-uterine progestine device (synthetic progestin containing IUDs,PI=0.16)
- •Oral contraceptives without estrogen (e.g. "mini-pills"), nonsynthetic progesterone only IUDs, female condoms, cervical shield, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy. Patients with psoriatic arthritis are not excluded.
- •Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
- •Subjects with preexisting or recent-onset central or peripheral nervous system demyelinating disorders at discretion of the investigator.
- •Significant medical problems, including but not limited to the following: uncontrolled hypertension (≥160 systolic and/or 95 diastolic mmHg), congestive heart failure [New York Heart Association status of class III or IV].
- •Subjects with a serum creatinine level exceeding 2.0 mg/dl (176.8μmol/l) at screening.
- •Screening total white blood cell (WBC) count <2,500/μl, or platelets <100,000/μl or neutrophils <1,500/μl or hemoglobin <8.5 g/dl.
- •Active systemic infections during the last two weeks (exception: common cold) prior to screening or any infection that reoccurs on a regular basis.
- •History of an ongoing, chronic or recurrent infectious disease including recurrent respiratory and/or urinary tract infections or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test at screening. Subjects with a positive or indeterminate QuantiFERON TB-Gold test may participate in the study if further full tuberculosis work up (according to local practice/guidelines) completed at least 12 weeks prior to first study drug administration establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to local country guidelines for at least 4 weeks prior to screening.
- •Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to screening.
- •History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
- •Current severe progressive or uncontrolled disease which in the judgment of the clinical investigator renders the subject unsuitable for the trial or puts the subject at increased risk.
- •Inability or unwillingness to undergo repeated venipuncture (e.g. because of poor tolerability or lack of access to veins).
- •Any medical or psychiatric condition which, in the investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
- •History or evidence of ongoing alcohol or drug abuse, within the last six months before screening.
- •Plans for administration of live vaccines during the study period or 6 weeks prior to screening.
- •No additional exclusions may be applied by the investigator, in order to ensure that the study population will be representative of all eligible subjects.
研究组 & 干预措施
Secukinumab Interval Shortening
Active Comparator
干预措施: Secukinumab (Drug)
Secukinumab 4-weekly
Active Comparator
干预措施: Secukinumab (Drug)
结局指标
主要结局
Number of Participants With PASI 90 Response at Week 32 for PPS
时间窗: at week 32
Number of participants with at least 90% improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).
Number of Participants With PASI 90 Response at Week 32
时间窗: at 32 weeks
Number of participants with at least 90% improvement from baseline. PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area\* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).
次要结局
- Comparative Dose Phase:Summary of IGA Score(Weeks 18, 22, 26, 30, 32)
- Selection Phase:Summary of PASI Total Score(at weeks 1,2,3,4,8, 12, 16)
- Comparative Dose Phase: Summary of PASI Total Score(Weeks 18, 22, 26, 30 and 32)
- Number of Patients Achieving DLQI Total Score <= 5 in the CDP(Weeks 4, 16, 18, 22, 26, 30, 32)
- Selection Phase: Summary of IGA Score(Weeks 4, 16)
- Selection Phase: Number of Participants Achieving (Psoriasis Area and Severity Index Score)PASI 50, 75, 90, 100(at weeks 1, 2, 3, 4, 8, 12 and 16)
- Number of Patients Achieving Dermatology Life Quality Index (DLQI) Scores of 0 or 1 by Visits in the CDP(Weeks 4, 16, 18, 22, 26, 30, 32)
- Comparative Dose Phase: Number of Participants Achieving Psoriasis Area and Severity Index Score (PASI) 90 and 100(at weeks 18, 22, 30, 32)
- Comparative Dose Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1(Weeks 18, 22, 26, 30, 32)
- Selection Phase: Number of Patients Achieving Investigator Global Assessment (IGA) 0 or 1(Weeks 4, 16)
研究者
研究点 (1)
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