NCT06980597招募中1 期
An Open-Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Allogeneic CAR-T Cell Therapy (OL-108) in the Treatment of Relapsed/Refractory Autoimmune Diseases
Beijing GoBroad Hospital2 个研究点 分布在 1 个国家目标入组 44 人开始时间: 2025年6月最近更新:
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
This study aims to characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy of OL-108 in relapsed/refractory autoimmune diseases.
详细描述
This is an open-label, single-arm, clinical study to evaluate the efficacy and safety of CAR-T therapy OL-108 in the treatment of Relapsed/ Refractory Autoimmune Disease such as SLE, IIM, SSc and AAV.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Adults aged 18-65 years old
- •Adequate organ function
- •Females of childbearing potential (FCBP) must have a negative pregnancy test at screening and must agree to use a highly effective contraceptive method starting from the time of lymphodepletion and for 2 years after dosing of the IMP
- •SLE specific:
- •a) Fulfilling the 1997 ACE SLE criteria/ 2012 SLICC criteria/ 2019 ACR/EULAR classification criteria of SLE; b) A positive ANA titer (≥ 1:80) and/or presence of anti-dsDNA, or anti-Sm antibodies; c) Active disease at screening, defined as SLEDAI-2K≥8 AND clinical SLEDAI-2K≥6, AND ≥1 organ system with a British Isles Lupus Assessment (BILAG) A score (severe disease activity) or ≥2 organ systems with a BILAG B score (moderate disease activity), AND PGA≥ 1; OR biopsy proven 2003 ISN/RPS class III/IV +/- class V lupus nephritis; d) relapsed or refractory to at least one immunosuppressant or biologic.
- •IIM specific:
- •a) Fulfilling the 2017 ACR/EULAR classification criteria for DM, PM, ADM, ASS and IMNM; b) Active disease as defined by at least one of the following criteria: at least one muscle enzyme > ULN in the past 4 weeks, active disease by EMG/muscle biopsy/MRI in the past 3 months, active DM rash; c)MMT < 142 and 2 of the following criteria: VAS patients Global ≥ 2 cm, VAS physician Global ≥ 2 cm, HAQ > 0.25, at least one muscle enzyme > 1.5x ULN, MDAAT ≥ 2 ; d) CDASI ≥14 if with skin involvement; e) At least one myositis-specific or associated antibody positive; f)relapsed or refractory to at least one immunosuppressant or biologic.
- •SSc specific:
- •a)Fulfilling the 2013 ACR/EULAR classification criteria of SSc; b) Active disease as defined by one of following: new or progressing skin manifestation/vital organ involvement within 6 months prior to screening, CRP≥6 mg/L, ESR≥28 mm/h, platelet ≥330 × 10⁹/L; c) mRSS score >10; d)relapsed or refractory to at least one immunosuppressant or biologic.
- •AAV specific:
- •Fulfilling the 2022 ACR/EULAR classification criteria for MPA/GPA; b) Presence of ANCA to either proteinase 3 or myeloperoxidase; c)At least one major or three non-major items or at least two renal items of hematuria and proteinuria on the BVAS; d)relapsed or refractory to at least one immunosuppressant or biologic.
排除标准
- •Active uncontrolled infection
- •Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load
- •Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load
- •HIV antibody positive
- •Syphilis antibody positive
- •Active tuberculosis, untreated or inadequately treated latent tuberculosis infection (LTBI)
- •History of serious infection within 3 months prior to screening (defined as requiring hospitalization or intravenous antimicrobial therapy), or history of oral antimicrobial therapy within 1 month prior to screening (e.g., viral infections, opportunistic infections, including but not limited to severe cytomegalovirus or herpes virus infections)
- •Congenital long QT syndrome or a corrected QTcF interval of ≥480 ms at screening (unless secondary to pacemaker or bundle branch block)
- •Uncontrolled hypertension (blood pressure ≥160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes or other endocrine diseases, severe chronic pulmonary disease, or other serious medical condition which is likely to significantly impair the patient's ability to tolerate the study treatment
- •history of organ transplant
- •Pregnancy or lactating women
- •Use of any other experimental medication within 4 weeks or 5 half-lives prior to start of study drug
- •Use of biologics within 3 months, stem cell transplant or CAR-T within 6 months prior to the start of study drug
- •Received live or attenuated vaccine within 4 weeks of Cycle 1 Day 1
- •Presence of other autoimmune or auto-inflammatory diseases that may affect study assessments, such as rheumatoid arthritis, gout, or active fibromyalgia syndrome.
- •Limited to patients diagnosed with SLE: patients with active neuropsychatric SLE
- •Limited to patients diagnosed with IIM: Severe involvement of respiratory muscles affecting ventilatory function; permanent muscle weakness related to IIM; other inflammatory or non-inflammatory myopathy: inclusion body myositis, infectious myopathy, metabolic myopathy, muscular dystrophy or a family history of muscular dystrophy, drug-induced or endocrine-induced myositis, and juvenile myositis
- •Limited to patients diagnosed with SSc: at risk for scleroderma renal crisis; SSc-associated gastric antral vascular ectasia; Severe gastrointestinal involvement leading to malabsorption or intestinal failure
- •Limited to patients diagnosed with AAV: Central nervous system vasculitis; Alveolar hemorrhage requiring invasive pulmonary ventilation
研究组 & 干预措施
OL-108
Experimental
干预措施: OL-108 (Biological)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: After OL-108 administration up to 30 days (Day 1-Day 30)
Adverse events will be assessed based on the CTCAE 5.0
Treatment emergent adverse event (TEAE) incidence and severity
时间窗: From lymphodepletion through study completion, up to 2 years
Adverse events will be assessed based on the CTCAE 5.0
次要结局
- Overall Response Rate(Baseline through study completion, up to 2 years)
- Cmax of OL-108(Baseline through study completion, up to 2 years)
- Tmax of OL-108(Baseline through study completion, up to 2 years)
- AUC 0-28 days of OL-108(Baseline through study completion, up to 2 years)
- Serum cytokines(From lymphodepletion till day 90)
- Level of Immunogenicity(Baseline through study completion, up to 2 years)
- Level of RCR(Baseline through study completion, up to 2 years)
研究者
Kai Hu
Professor
Beijing GoBroad Hospital
研究点 (2)
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