A Multi-Center, Randomized, Double-blind, Placebo-controlled, Multi-Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of SHR-1314 With Expanded Dose Finding in Subjects With Moderate-to-severe Plaque Psoriasis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 211
- 试验地点
- 12
- 主要终点
- Pharmacokinetics (PK) of SHR-1314 (Part A)
研究概览
简要总结
This is a multi-regional, randomized, double-blind, placebo-controlled, clinical trial to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of SHR-1314 in adults with moderate-to-severe plaque psoriasis.
详细描述
This study is a multiple dose escalating design to evaluate the safety, PK, and pharmacodynamics (PD) of multiple subcutaneous injections of SHR-1314. There are two parts in this study. The safety, PK, and PD will be evaluated in Part A, the dose escalation part. The efficacy and safety on different doses will be assessed in parallel-groups in Part B.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •Provide written informed consent before any study assessment is performed.
- •Male or female at least 18 years of age at screening.
- •At the time of randomization, moderate to severe plaque psoriasis, defined by:
- •PASI score of 12 or greater and
- •PGA score of 3 or greater and
- •BSA affected by plaque-type psoriasis of 10% or greater.
- •Subject is a candidate for systemic psoriasis therapy and/or phototherapy and/or chemo phototherapy.
排除标准
- •Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic, and guttate psoriasis) at screening.
- •Drug-induced psoriasis (i.e. new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at randomization.
- •Active systemic infections (other than common cold) during the two weeks before randomization (e.g., hepatitis), or serious infections requiring hospitalization and/or intravenous injection of antibiotic treatment within eight weeks from randomization.
- •Presence of other skin conditions (e.g. skin infections, seborrheic dermatitis) that in the judgement of the Investigator could interfere with assessment of psoriasis.
- •History of inflammatory bowel disease or have other ongoing active autoimmune diseases.
- •At screening, history or symptoms 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.
- •History of depression and/or suicidal ideation or behavior which in the opinion of the Investigator, makes the subject unsuitable for clinical study participation.
- •Any severe, progressive or uncontrolled medical condition at randomization that in the judgement of the Investigator prevents the subject from participating in the study.
- •Have a known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study.
- •Concurrent or recent use of psoriasis treatments/ medications.
- •Are currently enrolled in, or discontinued from a clinical trial involving an Investigational product (IP) within the last 4 weeks or at least 5 half-lives of the last dosing prior to randomization, whichever is longer; or concurrently enrolled (at randomization) in any other trials.
- •Have had a live attenuated vaccination within 12 weeks before randomization, or intend to have a live attenuated vaccination during the course of the study, or have participated in a vaccine clinical trial within 12 weeks prior to randomization.
- •Have evidence of positive test for hepatitis B, hepatitis C antibody, or human immunodeficiency virus (HIV) antibodies.
- •A positive test for hepatitis B is defined as 1) positive for hepatitis B surface antigen [HBsAg], or 2) positive for anti-hepatitis B core antibody [HBcAb+] but negative for hepatitis B surface antibody [HBsAb-].
- •History or evidence of active or latent tuberculosis at screening.
- •Have laboratory test values that are considered clinically significant at screening that, in the opinion of the Investigator, pose an unacceptable risk to the subject if participating in the study or of interfering with the interpretation of data.
- •Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test at screening or Day
- •Females of child bearing potential (defined as all females physiologically capable of becoming pregnant) and males who are unwilling or unable to use highly effective contraception during the study and 20 weeks after the last administration of investigational product (anticipated 5 half-lives).
- •History of alcohol or illicit drug abuse within the year prior to screening.
- •Are unwilling or unable to maintain their normal pattern of alcohol, caffeine, smoking, and exercise from the start to the end of the study.
- •Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the Investigator.
研究组 & 干预措施
240mg SHR-1314 (Part B)
SHR-1314 240mg, subcutaneously
干预措施: SHR-1314 (Biological)
80mg SHR-1314-Part A
SHR-1314 80mg, subcutaneously
干预措施: SHR-1314 (Biological)
80mg SHR-1314-Part A
SHR-1314 80mg, subcutaneously
干预措施: Placebo (Drug)
160mg SHR-1314-Part A
SHR-1314 160mg, subcutaneously
干预措施: SHR-1314 (Biological)
160mg SHR-1314-Part A
SHR-1314 160mg, subcutaneously
干预措施: Placebo (Drug)
240mg SHR-1314-Part A
SHR-1314 240mg, subcutaneously
干预措施: SHR-1314 (Biological)
240mg SHR-1314-Part A
SHR-1314 240mg, subcutaneously
干预措施: Placebo (Drug)
40mg SHR-1314 (Part B)
SHR-1314 40mg, subcutaneously
干预措施: SHR-1314 (Biological)
80mg SHR-1314 (Part B)
SHR-1314 80mg, subcutaneously
干预措施: SHR-1314 (Biological)
160mg SHR-1314 (Part B)
SHR-1314 160mg, subcutaneously
干预措施: SHR-1314 (Biological)
SHR-1314 Placebo (Part B)
SHR-1314 Placebo, subcutaneously
干预措施: Placebo (Drug)
结局指标
主要结局
Pharmacokinetics (PK) of SHR-1314 (Part A)
时间窗: From baseline through 24 weeks
Observed Maximum Serum Concentration Following Drug Administration (Cmax)
Percentage of Participants With Anti-SHR-1314 Antibodies (Part A)
时间窗: From baseline through 24 weeks
Percentage of participants with treatment-emergent positive anti-SHR-1314 antibodies was summarized by treatment group. Percentage was calculated based on the number of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-SHR-1314 antibodies / number of evaluable participants \* 100%.
Percentage of subjects who achieve Psoriasis Area Severity Index (PASI) score 75 (Part B)
时间窗: From baseline through 12 weeks
Percentage of subjects who achieve at least 75% improvement in the PASI (PASI 75)
Number of Participants With Clinically Significant Events (Part A)
时间窗: From baseline through 24 weeks
Clinically significant events were defined as abnormal laboratory values and/or adverse events that are related to treatment
次要结局
- Psoriasis Area Severity Index (PASI) score(From baseline through 24 weeks (Part A) or 36 weeks (Part B))
- Change of dermatology life quality index (DLQI) score(From baseline up to 12 weeks (Part A) or 36 weeks (Part B))
- Change from baseline in Body Surface Area (BSA)(From baseline through 12 weeks (Part A) or (Part B))
- Physician's Global Assessment (PGA) of 0 or 1 achievement(From baseline through 24 weeks (Part A) or 36 weeks (Part B))