A Non-inferiority Study on Dose Reduction of Adalimumab in Psoriasis Patients Who Are Overtreated
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 2
- 主要终点
- Validation of adalimumab dried blood spots
研究概览
简要总结
Recently, the optimal therapeutic serum trough level range of adalimumab was defined between 3,5 and 7,0 µg/ml in patients with plaque type psoriasis. An adalimumab serum through level above this therapeutic range did not add to clinical response. Based on this therapeutic window, the introduction of dose adjustments based on serum trough levels (therapeutic drug monitoring) will be further validated in a prospective controlled trial. Here, we aim to determine whether, in patients with a good clinical response and supratherapeutic adalimumab STLs, dose reduction based on therapeutic drug monitoring (TDM) is able to maintain the initial clinical outcome.
详细描述
In this study we investigate whether dose reduction of adalimumab in patients with supratherapeutic adalimumab Ctrough levels is non-inferior to standard dosing of adalimumab.
Before randomization, 3 subsequent evaluations of adalimumab Ctroughs will be executed. Patients will be included after signing informed consent and randomized if 2/3 subsequent measurements during screening show supratherapeutic Ctrough levels. Time point of randomization is considered baseline (week 0). PASI calculation will be performed by a blinded and independent physician.
In the concentration based arm, dosing frequency will be lowered to 40 mg every 3 weeks (33% reduction). In case of persistent supratherapeutic Ctroughs, a 50% dose reduction will be applied from week 12 onwards. In the standard based arm, patients will continue on standard dosing schedule of 40 mg every other week.
During each study visit PASI and IGA score will be evaluated by an independent and blinded physician and adverse events, and concomitant medications will be evaluated by a member of the study team. Ctrough is quantified at each visit; and anti-drug antibodies concentrations only if subtherapeutic concentrations are observed. Patients complete the Dermatology Life Quality Index (DLQI) and EuroQol-5D-5L instrument at each visit.
In addition, in a subset of patients in each treatment arm, additional sampling will be collected by dried blood spot sampling in order to build a PK(PD) model for adalimumab,
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
- Single (Outcomes Assessor)
盲法说明
PASI and IGA score will be performed by a blinded and independent physician.
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
- •Participants must be >18 years of age.
- •Participants must have a diagnosis of chronic plaque-type psoriasis for at least 6 months (with or without PsA), prior to the first administration of study intervention.
- •Participant must remain on a highly effective method of birth control during the study or during the entire treatment with adalimumab (whether with is longer)
- •Participants are considered eligible according to the following TB screening criteria:
- •Have no history of latent or active TB before screening
- •Have no signs or symptoms suggestive for active TB upon medical history and/or physical examination
- •Have had no recent close contact with a person with active TB
- •Participants must agree not to receive a live virus or live bacterial vaccination at least 3 months (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study intervention (except for varicella and MMR vaccines), during the study, or within 3 months after the last administration of study intervention.
- •Participants must avoid prolonged sun exposure and use of tanning booths or other ultraviolet light sources during study.
- •Participants must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study.
排除标准
- •Participants who have currently a predominant nonplaque forms of psoriasis (eg. Erythrodermic, guttate, pustular)
- •Participants who are pregnant, nursing or planning a pregnancy or fathering a child while enrolled in the study or within 12 weeks after receiving the last administration of study intervention
- •Participants who have received, or are expected to receive, any live virus or bacterial vaccination (with the exception of varicella or MMR vaccines) within 3 months (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study intervention, during the study, or within 12 weeks after the last administration of study intervention
- •Participants who have known allergies, hypersensitivity or intolerance to adalimumab or its excipients
- •Participants who have any malignancy or have a history of malignancy
- •Participants who are unable or unwilling to undergo multiple venapunctures
结局指标
主要结局
Validation of adalimumab dried blood spots
时间窗: Sampling at home on days 0, 3, 5, 7, 14, 21, 28, 35, 42 and 49 after adalimumab administration
Optimization of extraction protocol for adalimumab serum trough levels and anti-adalimumab antibody concentrations derived from dried blood spots (DBS)
Clinical response
时间窗: 1 year after inclusion
The proportion of patients in each group in clinical remission (absolute PASI \< 2) at year 1 after optimization
次要结局
- Cost-effectiveness of adalimumab dose tapering(1 year after inclusion)
- Quality adjusted life years(1 year after inclusion)
- Relapse(1 year after inclusion)
- Anti- drug antibodies against adalimumab(1 year after inclusion)
- Serum trough levels of adalimumab within the optimal therapeutic window(1 year after inclusion)
- Identify relevant parameters for PK-PD modeling(1 year after inclusion)