Investigating an mRNA CAR T-cell Therapy, Known as Descartes-08, as a Potential Approach to Treat Myasthenia Gravis

Официальное название

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Descartes-08 in Patients With Generalized Myasthenia Gravis (MG)

Обзор

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.

Вмешательства

• Биопрепарат Decartes-08
  Autologous mRNA CAR T-cell therapy
• Другое Placebo Drug
  infusion without Decartes-08

Первичные конечные точки

• Myasthenia Gravis Activities of Daily Living (MG-ADL) [Срок оценки: assessment at 4 months of study]

Критерии участия

Критерии включения

• 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 ≥ 6.
• 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,

Критерии исключения

• 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/mm3.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 23 центра

• A40 — Tucson
• A13 — Carlsbad
• A46 — Los Angeles
• A14 — Orange
• A21 — Aurora
• A50 — Washington D.C.
• A48 — Maitland
• A10 — Tampa
• … и ещё 15 центров

Испания · 3 центра

• A25 — Barcelona
• A26 — Barcelona
• A31 — Madrid

Turkey (Türkiye) · 2 центра

• A32 — Ankara
• A17 — Istanbul

Великобритания · 2 центра

• A33 — Birmingham
• A51 — Sheffield

Канада · 1 центр

• A18 — Toronto

Италия · 1 центр

• A23 — Rome

Польша · 1 центр

• A30 — Krakow

Сербия · 1 центр

• A24 — Belgrade

Идентификаторы

NCT: NCT06799247 · RNAC-MG-002 (AURORA)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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