A Dose-escalation and Safety Study of CID-103 Followed by a Randomized, Open-label, Parallel-arm Multi-dose Study Evaluating the Efficacy and Tolerability of CID-103 in Adults With Chronic Immune Thrombocytopenia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 75
- 试验地点
- 6
- 主要终点
- Safety and tolerability of CID-103
研究概览
简要总结
The goal of the global Phase 1/2 clinical trial is to evaluate whether CID-103, a novel anti-CD38 monoclonal antibody, is safe and effective in adults with chronic immune thrombocytopenia (ITP). The main questions the study aims to answer are:
- To evaluate the safety and tolerability of CID-103 in subjects with ITP with different increasing doses of CID-103.
- To further evaluate the safety and tolerability of CID-103 at two or three dose levels and to select an optimal dose and administration regimen for CID-103 for further study of clinical efficacy.
The study will be done in two parts:
Part A will test increasing doses of CID-103 to see how safe it is and how well people tolerate it. Researchers will also aim to find a safe dose range.
Part B will compare up to three different doses of CID-103 to see how well the medicine works and gather more safety and efficacy information. The goal is to find the optimal dose to use in future studies.
CID-103 is given through an intravenous (IV) infusion. During the study, participants may receive treatment for up to 6 months, followed by a post-treatment safety follow-up period to check for ongoing safety and effectiveness.
This study is an important step toward developing a new treatment for people living with chronic ITP. If CID-103 is found to be safe and effective, it could offer a new option for patients who do not respond well to current therapies.
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
- None
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
- •Male or female individuals aged 18 to 65 years at time of signing of ICF. Disease-related.
- •Diagnosed with ITP that has persisted for ≥ 3 months, diagnosed in accordance with The American Society of Hematology 2019 Guidelines for Immune Thrombocytopenia or the Updated International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia (as locally applicable).
- •Diagnosis of ITP supported by a prior response to an ITP treatment (other than a thrombopoietin receptor agonists [TPO-RA]) that achieved a platelet count of ≥ 30 x 10^9/L and a doubling of baseline measurement.
- •Has received at least two lines of SOC systemic treatment (i.e., corticosteroids and one other agent).
- •Has a mean platelet count ≤ 35 x 10^9/L on at least two measurements at least one week apart during screening.
- •If receiving standard background treatment for ITP, treatment should be stable in dose and frequency for at least four weeks prior to first dose of CID-
- •Adequate organ function.
- •Contraception: Female participants must either be non-pregnant or not breastfeeding and must have a negative pregnancy test. Male and female participants must meet the contraceptive requirements.
排除标准
- •Prior treatment with any anti-CD38 agent, or has been treated with anti-Bruton's tyrosine kinase (BTK), neonatal Fc receptor (FcRn) antagonist or complement inhibitor within three months prior to first dose of CID-
- •Use of IV immunoglobulin, subcutaneous immunoglobulin or anti-D immunoglobulin treatment within four weeks of screening.
- •Treatment with rituximab or splenectomy within the three months prior to first dose of CID-
- •Use of anticoagulants or any drug with antiplatelet effect (such as aspirin) within three weeks before screening.
- •Receiving other concurrent investigational therapies or have received investigational therapies within four weeks of the first dose of CID-103 or five half-lives (if shorter).
- •Active hemolytic anemia.
- •Diagnosed with severe chronic obstructive pulmonary disease (COPD), Global Initiative for Chronic Obstructive Lung Disease (GOLD Stage 3 or 4) or asthma.
- •Has been diagnosed with myelodysplastic syndrome or other active malignancy.
- •Known / clinically significant amyloidosis.
- •Has a history of any thrombotic or embolic event within six months before screening.
- •A history or evidence of cardiovascular risk including left ventricular ejection fraction < 50%, clinically significant uncontrolled ventricular arrhythmia, acute coronary syndrome history, coronary angioplasty or stenting within six months, current ≥ Class III congestive heart failure (NYHA guidelines), and treatment refractory hypertension.
- •Clinically significant medical history or ongoing chronic illness.
- •Known active infection with hepatitis B (HBV) (surface antigen) or infection with hepatitis C (HCV) in absence of sustained virologic response.
- •History of known or suspected immunosuppression.
- •Known active infection with human immunodeficiency virus (HIV) and CD4+ T cell count < 350/μL.
- •Karnofsky Performance Status ≤ 70.
研究组 & 干预措施
Part B (Randomized Dose Exploration) high-dose cohort
Each participant will receive selected high-dose. Once approximately 8 evaluable subjects per arm have completed approximately six weeks of treatment, an initial review of safety and efficacy will be conducted by the SMC to determine if there is one or more sub-optimal dose(s) that should be closed to further recruitment or if dose / regimens require adjustment.
干预措施: CID-103 (Drug)
Part B (Randomized Dose Exploration) intermediate-dose cohort
Each participant will receive selected intermediate-dose. Once approximately 8 evaluable subjects per arm have completed approximately six weeks of treatment, an initial review of safety and efficacy will be conducted by the SMC to determine if there is one or more sub-optimal dose(s) that should be closed to further recruitment or if dose / regimens require adjustment.
干预措施: CID-103 (Drug)
Part B (Randomized Dose Exploration) low-dose cohort
Each participant will receive selected low-dose. Once approximately 8 evaluable subjects per arm have completed approximately six weeks of treatment, an initial review of safety and efficacy will be conducted by the SMC to determine if there is one or more sub-optimal dose(s) that should be closed to further recruitment or if dose / regimens require adjustment.
干预措施: CID-103 (Drug)
Part A (Dose Escalation) Cohort 1- 30 mg/30 mg
This is the initial dose cohort with accelerated dose escalation design. If a Grade ≥ 2 AE is reported in the cohort, the cohort will expand to three subjects and the study will then convert to a standard 3+3 design.
干预措施: CID-103 (Drug)
Part A (Dose Escalation) Cohort 1- 30 mg/150 mg
This is the second dose cohort with accelerated dose escalation design. If a Grade ≥ 2 AE is reported in the cohort, the cohort will expand to three subjects and the study will then convert to a standard 3+3 design.
干预措施: CID-103 (Drug)
Part A (Dose Escalation) Cohort 1- 150 mg/300 mg
This is the third dose cohort with accelerated dose escalation design. If a Grade ≥ 2 AE is reported in the cohort, the cohort will expand to three subjects and the study will then convert to a standard 3+3 design.
干预措施: CID-103 (Drug)
Part A (Dose Escalation) Cohort 1- 150 mg/600 mg
This is the fourth dose cohort with standard 3+3 design.
干预措施: CID-103 (Drug)
Part A (Dose Escalation) Cohort 1- 150 mg/900 mg
This is the fifth dose cohort with standard 3+3 design.
干预措施: CID-103 (Drug)
结局指标
主要结局
Safety and tolerability of CID-103
时间窗: 10 months
* Occurrence of DLTs (Part A only) * Frequency of TEAEs * Related AEs * Grade 3/4 AEs * Serious adverse events (SAEs) * Fatal AEs * AEs leading to CID-103 discontinuation up to Week 12 * Percentage of subjects with at least one treatment-related Grade ≥ 3 TEAE, SAE or AE leading to CID-103 discontinuation up to Week 12 (Part B only)
Platelet response
时间窗: 12 weeks
A platelet count ≥ 50 x 10\^9/L and ≥ 20 x 10\^9/L above baseline achieved on at least two consecutive measurements at least seven days apart.
次要结局
- Platelet count(12 weeks)
- Complete platelet response(12 weeks)