A Randomized, Double-blinded, and Placebo-controlled Phase I/II Clinical Study of AK101 in Subjects With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Incidence of treatment emergent adverse events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and the preliminary efficacy of AK101，an anti-IL-12/23p40 monoclonal antibody, when administered subcutaneously in subjects with moderate-to-severe plaque psoriasis.
详细描述
This was a single-center, randomized, double-blind, placebo-controlled trial which consisted of a dose escalation phase (Phase I) and a dose expansion phase (Phase II)..
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
- 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
- •Have had Plaque Psoriasis diagnosed at least 6 months prior to screening.
- •Clinical diagnosis of stable plaque psoriasis with involvement of ≥ 10% body surface area. Psoriasis area and severity index(PASI) ≥
- •Physicians Global Assessment score ≥
- •Patients who have received systemic therapy or phototherapy, or who have been allowed by the investigator to receive systemic therapy or phototherapy.
- •Women of childbearing potential should not be in pregnancy or lactation, men and women of childbearing potential must agree to use adequate birth control measures during study participation and for 6 months after the last dose of study treatment.
- •Ability to provide written informed consent and to be compliant with the schedule of protocol assessments.
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures as specified in the protocol.
排除标准
- •Had nonplaque forms of psoriasis (e.g., Guttate, erythrodermic, or pustular).
- •Had other active skin diseases or skin infections (e.g., bacterial, fungal or viral infection) that could affect psoriasis evaluation.
- •Had Imaging diagnosis of pulmonary infection or fibrosis during the 3 months prior to screening.
- •History or evidence of active or latent tuberculosis at screening.
- •Serious systemic infections or local infections during the 2 months prior to screening.
- •History of cancer, including solid tumors and hematological malignancies (except basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved).
- •Known allergy or hypersensitivity to any biologic therapy at screening that would pose an unacceptable risk to the subject if participating in this study.
- •History of alcohol or drug abuse.
- •History or known presence of recurrent or chronic infection (e.g., hepatitis B, or C, human immunodeficiency virus [HIV], syphilis, TB).
- •Had received any DMARDs (e.g., anti-malaria drug, retinoids, interferon, lithium) during 2 weeks prior to screening.
- •Had received any physical therapy (e.g., PUVA, ultra-violet therapy, tanning beds) during 2 weeks prior to screening.
- •Had received any systemic psoriasis therapy (e.g., glucocorticoid, retinoids, ciclosporin, methotrexate, or tripterygium) during 4 weeks prior to screening.
- •Had Enrolled in any other trials during 3 months prior to screening or concurrently enrolled in any other trials.
- •Had received previous treatment with any anti-IL-12/IL-23, IL-12, IL-23, IL-17 therapy for the treatment of psoriasis or psoriatic arthritis.
- •Had received previous treatment with natalizumab or any other drugs that regulate B cells or T cells (rituximab, abatacept, alemtuzumab) during 12 months prior to screening.
- •Had received other biologic therapy (e.g., TNF inhibitor) during 6 months prior to screening.
研究组 & 干预措施
Phase I: AK101 45 mg
Biological: AK101 AK101 45 mg on Week 0 and 4 by subcutaneous injection
干预措施: AK101 (Biological)
Phase I: AK101 135 mg
Biological: AK101 AK101 135 mg on Week 0 and 4 by subcutaneous injection
干预措施: AK101 (Biological)
Phase I: AK101 270 mg
Biological: AK101 AK101 270 mg on Week 0 and 4 by subcutaneous injection
干预措施: AK101 (Biological)
Phase I: Placebo
Biological: Placebo Placebo on Week 0 and 4 by subcutaneous injection
干预措施: placebo (Biological)
Phase II: AK101 45 mg
Biological: AK101 AK101 45 mg on Week 0, 4 and 16 by subcutaneous injection
干预措施: AK101 (Biological)
Phase II: AK101 90 mg
Biological: AK101 AK101 90 mg on Week 0, 4 and 16 by subcutaneous injection
干预措施: AK101 (Biological)
Phase II: AK101 135 mg
Biological: AK101 AK101 135 mg on Week 0, 4 and 16 by subcutaneous injection
干预措施: AK101 (Biological)
Phase II: Placebo to AK101
Drug: Placebo Placebo on Week 1 and 4 by subcutaneous injection, and then AK101 on Week 12 16 by subcutaneous injection
干预措施: AK101 (Biological)
Phase II: Placebo to AK101
Drug: Placebo Placebo on Week 1 and 4 by subcutaneous injection, and then AK101 on Week 12 16 by subcutaneous injection
干预措施: placebo (Biological)
结局指标
主要结局
Incidence of treatment emergent adverse events (TEAEs)
时间窗: From the time of signing informed consent till Week 16 for Phase I or Week 28 for Phase II
次要结局
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose till Week 16 for Phase I or Week 28 for Phase II)
- Number of participants who achieved ≥ 75% reduction in Psoriasis Area and Severity Index (PASI75)(At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II))
- Minimum observed concentration (Cmin) of AK101(From first dose till Week 16 for Phase I or Week 28 for Phase II)
- Number of participants who achieved ≥ 90% reduction in PASI (PASI90)(At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II))
- Area under the curve (AUC) of AK101(From first dose till Week 16 for Phase I)
- Change From Baseline in the Physician Global Assessment (PGA)(At Week 2, 4, 8, 12, 16, 20 (Phase II), 24 (Phase II) and 28 (Phase II))
- Maximum observed concentration (Cmax) of AK101(From first dose till Week 16 for Phase I or Week 28 for Phase II)