A Randomized, Double-blind, Multicenter Study Assessing Short and Long-term Efficacy, Safety, and Tolerability of Sub-cutaneous Secukinumab in Subjects of Body Weight 90 kg or Higher With Moderate to Severe Chronic Plaque-type Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 331
- 试验地点
- 1
- 主要终点
- Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set)
研究概览
简要总结
The purpose of this study is to assess secukinumab high dose (every 2 weeks) vs standard dose (every 4 weeks) in heavy body weight subjects with moderate to severe plaque psoriasis.
详细描述
A 52-week multicenter, randomized, double-blind, parallel-group trial in 331 subjects with moderate to severe chronic plaque-type psoriasis of body weight 90 kg or higher at time of randomization.
This study consisted of 4 periods: screening (up to 4 weeks), treatment Period 1 (16 weeks), treatment Period 2 (36 weeks), and post-treatment follow-up (8 weeks).
Subjects were randomized using a 1:1 ratio to the following groups: Secukinumab 300 mg every 2 weeks; Secukinumab 300 mg every 4 weeks.
In addition, subjects from the 300 mg every 4 weeks group who did not achieve Psoriasis Area Severity Index (PASI) 90 response at Week 16 were reassigned using a 1:1 ratio to either remain on secukinumab 300 mg every 4 weeks or receive secukinumab 300 mg every 2 weeks starting at Week 16, until the end of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Written informed consent must have been obtained before any assessment was performed. Where relevant, a legal representative will also have signed the informed study consent according to local laws and regulations.
- •Subjects must have been able to understand and communicate with the investigator and comply with the requirements of the study.
- •Men or women at least 18 years of age at time of screening.
- •Body weight of ≥ 90 kg at the time of randomization.
- •Chronic plaque-type psoriasis present for at least 6 months and diagnosed before randomization.
- •Moderate to severe psoriasis as defined at randomization by:
- •Psoriasis Area and Severity Index (PASI) score of 12 or greater, and
- •Investigator's Global Assessment (IGA) mod 2011 score of 3 or greater (based on a static scale of 0 - 4), and
- •Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater.
- •Candidate for systemic therapy. This is defined as a subject having moderate to severe chronic plaque-type psoriasis that is inadequately controlled by:
- •topical treatment and/or,
- •phototherapy and/or,
- •previous systemic therapy.
排除标准
- •Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at screening or Randomization.
- •Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to be adhered to. Subjects not willing to limit ultraviolet (UV) light exposure (e.g., sunbathing and / or the use of tanning devices) during the course of the study will be considered not eligible for this study since UV light exposure is prohibited. Note: administration of live vaccines 6 weeks prior to Randomization or during the study period is also prohibited.
- •Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting Interleukin-17 (IL-17) or the IL-17 receptor.
- •Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 4 weeks until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations.
- •Pregnant or nursing (lactating) women
- •History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (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).
- •History of hypersensitivity to any of the study drug constituents.
研究组 & 干预措施
Secukinumab 300 mg every 2 weeks (Q2W)
2 injections of secukinumab 150 mg once weekly up to week 4 and thereafter every 2 weeks. Subjects remained on secukinumab 300 mg every 2 weeks until the end of treatment.
干预措施: secukinumab 150 mg (Drug)
Secukinumab 300 mg every 4 weeks (Q4W)
2 injections of secukinumab 150 mg once weekly up to week 4 and thereafter Q4W. Includes both subjects randomized to remain on Q4W the entire treatment period, and subjects that were Psoriasis Area and Severity Index (PASI) 90 responders at Week 16 from the secukinumab 300 mg Q4W possible up-titrate group.
干预措施: secukinumab 150 mg (Drug)
Secukinumab 300 mg every 4 weeks non-responders up-titration (Q4W NR up)
2 injections of secukinumab 150 mg once weekly up to week 4, then Q4W up to Week 16 and thereafter Q2W. Includes Psoriasis Area and Severity Index (PASI) 90 non-responders (NR) at Week 16 from the secukinumab 300 mg Q4W possible up-titrate group (subjects randomized to switch to Q2W if PASI 90 non-responder at Week 16).
干预措施: secukinumab 150 mg (Drug)
结局指标
主要结局
Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set)
时间窗: 16 weeks
A subject was considered as a PASI 90 responder if s/he achieved a reduction of 90% or more of the PASI score, compared to baseline, at a given time point.The head, trunk, upper limbs and lower limbs were assessed separately for erythema, thickening, and scaling. PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a theoretic maximum of 72.0, i.e., higher scores represent more severity.
次要结局
- Percentage of Subjects Who Achieve Investigator Global Assessment (IGA Modified 2011) Score of 0 or 1 - Week 16 (Full Analysis Set)(16 weeks)
- Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set)(Adverse events were reported from first dose of study treatment until end of study treatment plus 8 weeks post treatment, up to a maximum timeframe of 470 days.)