NCT06799247进行中（未招募）3 期
A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Descartes-08 in Patients With Generalized Myasthenia Gravis (MG)
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 128
- 试验地点
- 81
- 主要终点
- Myasthenia Gravis Activities of Daily Living (MG-ADL)
研究概览
简要总结
The AURORA Study is evaluating the safety, tolerability, and efficacy of an investigational mRNA CAR T-cell therapy known as Descartes-08 in adults with acetylcholine receptor autoantibody -positive generalized myasthenia gravis. Part 1 of the study will last around 6 months. For eligible participants, Part 2 will last around 8 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
first part of the study is double blinided and the second part of the study is open label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be at least 18 years of age.
- •Patient must have generalized myasthenia gravis (gMG), Myasthenia Gravis Foundation of America (MGFA) clinical classification grades 2-4 at the time of Sscreening.
- •MG-Activities of Daily Living (MG ADL) total score ≥
- •Concomitant immunosuppressive drugs must be deemed necessary by the investigator. The dose must be stable for a minimum of 8 weeks prior to Baseline visit.
- •If a patient is using corticosteroids, the daily dose should not exceed 40 mg/day of prednisone equivalent. The dose must have been stable for a minimum of 8 weeks prior to Baseline visit.
- •Acetylcholine receptor autoantibody (anti-nAChR) titer or anti-AChR cluster antibody must be above the reference laboratory upper normal limit (UNL) and documented within the past 10 years of screening.
- •Patient must be willing to return for all study visits.
- •Patient must be able to give written informed consent.
- •Women of childbearing potential must agree to use highly effective birth control from Screening until 14 days post last dose of Descartes-08,
排除标准
- •Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient.
- •Diagnosis of gMG within 12 months of screening.
- •No history of systemic treatment for gMG other than acetylcholine esterase inhibitors.
- •Diagnosis of a neuromuscular disease other than gMG.
- •Patient is pregnant or lactating.
- •Treatment with intravenous immunoglobulin (IVIG) or plasma exchange within 4 weeks prior to the Baseline visit.
- •Treatment with rituximab or ocrelizumab within 12 months prior to Baseline visit; treatment with calcineurin inhibitors (e.g. tacrolimus, cyclosporine, cyclophosphamide), Neonatal Fc receptor antagonists, and/or other biologics within 3 weeks prior to planned leukapheresis and within 8 weeks prior to Baseline visit.
- •The patient has started treatment with a complement 5a (C5a) inhibitor, such as eculizumab, within 8 weeks of Baseline visit. (NOTE: patients who have been receiving a C5a inhibitor for more than 8 weeks and meet other criteria for enrollment are eligible for treatment).
- •Prior treatment with B-cell maturation antigen (BCMA)-directed therapy (e.g. monoclonal antibody, T-cell engager, or chimeric antigen receptor T-cell [CAR-T]).
- •Abnormal prothrombin (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) increased > 1.5-fold above the normal range at Screening or patient is on anticoagulation therapy (except in cases of elevated PTT with documented lupus anticoagulant; or in patients who have been on stable doses of anticoagulation therapy for more than 6 months of venous thromboembolism (VTE) diagnosis; or in patients on stable doses of anticoagulation therapy for at least 8 weeks of atrial fibrillation diagnosis; these conditions will not be exclusionary unless, in the investigator's opinion, they make participation in the study unsafe).
- •Absolute neutrophil count (ANC) < 1000 cells/microliter.
- •Hemoglobin < 8.0 g/dL.
- •Platelets < 50,000/mm
- •Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3x above normal.
- •Creatine clearance less than 30 mL/min.
- •History of primary immunodeficiency, organ, or allogeneic bone marrow transplant.
- •Patients must be seronegative for hepatitis B surface antigen.
- •Patients must be seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patients must be tested for the presence of viremia by reverse transcriptase polymerase chain reaction (RT-PCR) and must be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.
- •History of positive human immunodeficiency virus (HIV) or positive HIV at screening.
- •Active tuberculosis or positive QuantiFERON test at screening.
- •Any other clinical or laboratory abnormality that, in the opinion of the investigator, may jeopardize the subject's ability to participate in the study or could affect study outcome.
- •Any active significant cardiac or pulmonary disease that, in the opinion of the Principal Investigator, is significant and/or uncontrolled.
- •Note: Patients with asthma and chronic obstructive pulmonary disease (COPD) controlled with inhaled medications are allowed.
- •History of malignancy that required treatment in the past 3 years, except for squamous cell carcinoma, basal cell carcinoma of the skin, or breast or early-stage colon cancer that is surgically removed and did not require adjuvant chemotherapy or radiotherapy.
- •Treatment with any investigational agent 4 weeks prior to screening or 5 half-lives of the investigational drug (whichever is longer).
- •Receipt of a live vaccination within 4 weeks prior to Baseline visit or intent to receive live vaccination during the study (Note: messenger RNA [mRNA]-based vaccines such as those against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not considered live; likewise, the Janssen Covid-19 vaccine is not live).
- •History of significant recurrent infections or any active infection that in the opinion of the Investigator may interfere with the patient's participation in the opinion of the investigator.
- •Any known psychiatric illness that in the opinion of the Investigator, may interfere with the patient's participation in the study in the opinion of the investigator.
研究组 & 干预措施
Decartes-08
Experimental
This group will undergo leukapheresis and receive manufactured Decartes-08
干预措施: Decartes-08 (Biological)
Placebo
Placebo Comparator
This group will receive placebo
干预措施: Placebo Drug (Other)
结局指标
主要结局
Myasthenia Gravis Activities of Daily Living (MG-ADL)
时间窗: assessment at 4 months of study
To evaluate the efficacy of Descartes-08 as assessed by the proportion of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders at Month 4.
次要结局
未报告次要终点
研究者
研究点 (81)
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