An Open-label, Multi-center, Phase 1/2 Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Participants With Relapsing Multiple Sclerosis With Breakthrough Disease Activity During Previous Treatment With a Highly Efficacious Therapy
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 28
- 试验地点
- 36
- 主要终点
- Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
This is an open-label, multi-center, non-confirmatory study to assess the safety, efficacy, and cellular kinetics of YTB323 in approximately 28 participants with Relapsing Multiple Sclerosis (RMS) with breakthrough disease activity during previous treatment with a highly efficacious therapy (BD-HET). The study design utilizes an ascending single dose design consisting of 3 sentinel cohorts followed by an expansion cohort.
详细描述
All participants in this study will receive YTB323. Both the participant and the study doctor will know the participant is getting YTB323. Participants will be given one dose of YTB323. Different groups of participants may receive a higher dose of YTB323, if proven to be safe for every participant at the lower dose. Participants are in this study for 2 years and will be followed for an additional 13 years in a long-term follow up study. The main question this trial is designed to answer: Is YTB323 treatment safe for participants with relapsing MS?
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study
- •Adequate renal, hepatic, cardiac, hematological, and pulmonary function
- •Male or female participants, ≥18 years to ≤60 years at screening, with diagnosis of RMS according to the 2017 McDonald diagnostic criteria Evidence of recent (i.e. within 1 year) breakthrough disease activity while at least 6 months on a highly efficacious therapy (any of the following): rituximab (Rituxan®), ocrelizumab (Ocrevus®), natalizumab (Tysabri®), ofatumumab (Kesimpta®), ublituximab (Briumvi®) or evidence of breakthrough disease activity within 2 years after the latest alemtuzumab infusion (Lemtrada®).
- •Evidence of breakthrough disease activity is defined as one or more of the following:
- •Confirmed Clinical MS relapse
- •Persistent radiological activity defined by one of the following:
- •≥2 T1 gadolinium-enhancing lesions on a single MRI scan
- •≥1 T1 gadolinium-enhancing lesions on two or more separate MRI scans
- •≥2 new T2 lesions compared to a previous scan within a period ≤1 year
- •Ambulatory patients (EDSS of 3 to 6 points, inclusive assessed outside of relapse)
- •Disease duration less than 15 years
- •Participants must receive or be current on all recommended vaccinations according to institutional, local, or global guidelines for immunocompromised patients at least 6-weeks prior to lymphodepletion
排除标准
- •Diagnosis of primary progressive multiple sclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria at screening
- •History of or current clinically significant CNS disease (e.g. stroke, traumatic brain or spinal injury, history or presence of myelopathy) or neurological disorders which may mimic MS or ICANS at screening
- •Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, New York Heart Association (NYHA) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 6 months prior to screening), neurological disorders other than MS (including seizure disorders even when well controlled), psychiatric, pulmonary (including, history of or active severe respiratory disease, including Chronic Obstructive Pulmonary Disease, interstitial lung disease or pulmonary fibrosis), renal, hepatic, endocrine, metabolic (e.g. severe hypoproteinemia due to nephrotic syndrome), hematological disorders or gastrointestinal disease that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant, prior to screening
- •Have donated blood or experienced a loss of blood > 400 mL within 3 months prior screening, or longer if required by local regulations
- •Any prior stem cell therapy or organ transplantation or gene therapy
- •Any contraindications to LP, including but not limited to:
- •Known or suspected structural abnormality of the lumbar spine that, in the opinion of the Investigator, may interfere with the performance of the LP, or increase the risk of the procedure for the participant
- •Presence of risk for increased or uncontrolled bleeding including, but not limited to, vascular abnormalities or neoplasms at or near the LP site, disorders of the coagulation cascade, platelet function, or platelet count
- •Participants on anticoagulants (e.g., warfarin) or antiplatelets [except for low-dose aspirin (100 mg/day or lower) and low-dose ibuprofen (600 mg/day or lower) which are allowable], are not eligible to participate
- •Participants not willing or able to take MRI scans as per protocol. Unable to undergo MRI due to for example claustrophobia, or presents absolute contraindications to MRI (e.g., metallic implants, metallic foreign bodies, pacemaker, defibrillator)
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
YTB323 Cohort 4
Participants will receive one dose of YTB323
干预措施: rapcabtagene autoleucel (YTB323) (Biological)
YTB323 Cohort 1
Participants will receive one dose of YTB323
干预措施: rapcabtagene autoleucel (YTB323) (Biological)
YTB323 Cohort 2
Participants will receive one dose of YTB323
干预措施: rapcabtagene autoleucel (YTB323) (Biological)
YTB323 Cohort 3
Participants will receive one dose of YTB323
干预措施: rapcabtagene autoleucel (YTB323) (Biological)
结局指标
主要结局
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Day 1 through Year 2
Incidence of dose limiting toxicities (DLTs), AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs), laboratory parameters, neurological status and magnetic resonance (MRI) of the brain and spinal cord qualifying and reported as AEs.
次要结局
- Measure of Disability: Expanded Disability Status Scale (EDSS).(Day 1 through Year 2)
- Measure of Disability: Short Form Health Survey (SF-36 v2)(Day 1 through Year 2)
- Measure of Disability: Timed 25 Foot Walk (T25FW)(Day 1 through Year 2)
- Measure of Disability: 9 Hole Peg Test (9HPT)(Day 1 through Year 2)
- Measure of Disability: Symbol Digit Modalities Test (SDMT)(Day 1 through Year 2)
- Measure of Disability: Fatigue Symptoms and Impacts Questionnaire - Relapsing Multiple Sclerosis (FSIQ-RMS)(Day 1 through Year 2)
- Number of new and enlarging T2 lesions and Gd-enhancing T1 Lesions(Day 1 through Year 2)
- Plasma Pharmacokinetics (PK) of YTB323 - CMAX(Day 1 through Year 2)
- Plasma Pharmacokinetics (PK) of YTB323 - AUC(Day 1 through Year 2)
- Plasma Pharmacokinetics (PK) of YTB323 - Tmax(Day 1 through Year 2)
- Plasma Pharmacokinetics (PK) of YTB323 - Clast(Day 1 through Year 2)
- Plasma Pharmacokinetics (PK) of YTB323 - Tlast(Day 1 through Year 2)
- Safety data including dose limiting toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs) from each dose level(Day 1 through Year 2)
- Humoral Immunogenicity of YTB323(Day 1 through Year 2)
- Cellular Immunogenicity of YTB323(Day 1 through Year 2)