investigating an mrna car t-cell therapy, known as descartes-08, as a potential approach to treat myasthenia gravis

Conditions: Myasthaenia Gravis

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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, exclusion criteria: * 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.

Keywords: myasthenia gravis car-t therapy cell therapy decartes-8 bmca b cell maturation antigen