RESET-MS: A Phase 1/2, Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T Cells (CABA-201) in Participants With Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 入组人数
- 12
- 主要终点
- Primary (Part A: Dose Escalation) incidence and severity of adverse events
研究概览
简要总结
RESET-MS: A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of Autologous CD19-specific Chimeric Antigen Receptor T cells (CABA-201) in Participants with Multiple Sclerosis
详细描述
This is a Phase 1/2, open-label study designed to evaluate the safety, tolerability, and efficacy of different doses of CABA-201 in adult participants with MS to determine an appropriate dose for future studies. Any participant who receives CABA-201 will be followed after infusion for 156 weeks. Two cohorts of participants will be studied based upon their MS diagnosis.
- Relapsing MS Cohort (RMS Cohort): Participants with active relapsing MS, including relapsing remitting MS (RRMS) and relapsing secondary progressive MS (SPMS) that is treatment-resistant
- Progressive MS Cohort (PMS Cohort): Participants with worsening progressive MS, including primary progressive MS (PPMS) or non-relapsing SPMS that is treatment-resistant
The study will consist of 2 parts: Part A (dose escalation) and Part B (dose expansion).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The main inclusion criteria include the following:
- •Able to provide informed consent.
- •Age ≥18 and ≤60 years of age.
- •Diagnosis of MS per the revised 2017 McDonald criteria (Thompson et al, 2018).
- •For participants with relapsing forms of MS only (RMS Cohort):
- •Moderate degree of previously accumulated disability as measured by the Expanded Disability Status Scale (EDSS)
- •Documentation of clinical relapse or a positive historical gadolinium (Gd)-enhancing magnetic resonance imaging (MRI) scan prior to Screening
- •Prior treatment with a high-efficacy therapy or prior treatment failure of oral therapies
- •For participants with progressive forms of MS only (PMS cohort):
- •Moderate Disability as measured by EDSS
- •Presence of abnormal function on protocol specified EDSS Functional Systems Scale
- •Objective worsening of disease prior to Screening while on standard of care therapy
- •Clinical stability by vital signs assessment at the time of screening
排除标准
- •The main exclusion criteria include the following:
- •History of fulminant MS
- •Clinically significant concomitant central nervous system pathologies which, in the Investigator's judgement, may confound the ability to interpret study results or complicate identification or evaluation of neurotoxicity, including but not limited to:
- •Any history of seizure disorder, even if well-controlled on antiepileptics
- •History of progressive multifocal leukoencephalopathy
- •Active, inflammatory autoimmune disorder other than MS requiring immunomodulatory therapies
- •a. Positive human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or hepatitis B surface antigen test, or evidence of active or chronic tuberculosis (TB) at Screening or other chronic viral infections as described in the protocol
- •Use of the following therapies:
- •Any prior or concurrent exposure to mitoxantrone, alemtuzumab, total lymphoid irradiation
- •Cladribine within 1 year of Screening
- •Any investigational agent within 4 weeks or 5 half-lives of Screening, whichever is longer
- •Other pre-specified Disease-Modifying Therapies be discontinued by the time of pre-conditioning or earlier as described in the protocol
- •Known malignancy or a history of malignancy
- •Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, psychiatric, cardiac, or concomitant neurological disease, including severe (requiring medical intervention) and uncontrolled infections
- •Chronic pulmonary disease
- •Impaired cardiac function or clinically significant cardiac disease
- •Prior engineered T cell therapy involving permanent gene modification
- •Prior solid organ (heart, liver, kidney, lung) transplant or hematopoietic stem cell transplant.
研究组 & 干预措施
Relapsing MS Cohort
干预措施: CABA-201 (Biological)
Progressive MS Cohort
干预措施: CABA-201 (Biological)
结局指标
主要结局
Primary (Part A: Dose Escalation) incidence and severity of adverse events
时间窗: Up to 28 days after CABA-201 infusion
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs.
Primary (Part B: Dose Expansion) incidence of and severity of adverse events in order to confirm the dose(s) of CABA-201
时间窗: Up to 28 days after CABA-201 infusion
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal result of an investigation), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. The term AE is used to include both serious and non-serious AEs.
次要结局
- Part A and Part B: To evaluate the incidence and severity of adverse events(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: To characterize the pharmacodynamics (PD)(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: To characterize the pharmacokinetics (PK)(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: To evaluate disease related biomarkers(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: To evaluate the effects of CABA-201 on MS disease activity as measured by Magnetic Resonance Imaging (MRI)(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: The effects of CABA-201 on MS disease activity as measured by EDSS(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: To evaluate the effect of CABA-201 on use of subsequent MS-related therapy(Up to 156 weeks after CABA-201 infusion)
- Part A and Part B: To evaluate the effect of CABA-201 on patient reported and health outcomes as measured by SF-36 v2(Up to 156 weeks after CABA-201 infusion)