Descartes-08, an investigational autologous RNA-engineered chimeric antigen receptor T-cell therapy (rCAR-T) has been dosed with the first participant in phase 2b randomized controlled trial.
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In recent news, Cartesian Therapeutics has dosed the first participant with Descartes-08, an investigational autologous RNA-engineered chimeric antigen receptor T-cell therapy (rCAR-T), in its phase 2b randomized controlled trial (NCT04146051) for myasthenia gravis (MG).1 The trial is likely to be the first ever placebo-controlled clinical trial for an engineered cell therapy and the most advanced cell therapy investigation in clinical development for any autoimmune disease.
The therapy will be administered as 6 weekly infusions and will not require preconditioning chemotherapy. Patients who initially receive treatment with the placebo will have the opportunity to crossover to treatment with Descartes-08 later on. The trial’s primary end point is the proportion of patients achieving a 6 point or greater improvement in MG Activities of Daily Living score, assessed at 12 weeks.
The multicenter, placebo-controlled trial is expected to enroll approximately 30 patients aged 18 years or older with generalized MG for whom immunosuppressive drugs have been deemed necessary by the trial’s investigator. The trial includes seronegative patients and excludes patients who are pregnant, lactating, or have a major chronic illness that is not well managed and deemed to increase the risk of participation. The trial is currently recruiting at several locations in the US with an estimated completion date of December 1, 2023.
“As a physician who treats patients with myasthenia, I have been impressed by the magnitude and duration of responses seen in the phase 2a trial of Descartes-08 in MG,” Tahseen Mozaffar, MD, professor of neurology at University of California, Irvine, said in a statement.1 “A tantalizing observation is that, after a 6-week course of Descartes-08, clinical responses continue to persist for many months and counting. RCTs are the gold standard for clinical trials, and I commend Cartesian for further studying Descartes-08 with this rigorous design.”
Descartes-08 is comprised of patients’ own T-cells that have been modified ex-vivo with RNA to target B-Cell Maturation Antigen (BCMA). The use of RNA engineering is intended to avoid risks of genomic integration associated with DNA-based CAR-T therapies and to allow for control of pharmacokinetics.
Secondary end points include comparisons of Descartes-08 versus the placebo on several MG assessments; comparisons of Descartes-08 versus the placebo on MG assessments for patients who crossover; the change in titer of myasthenia specific autoantibody titers; and the effect of single or multiple infusions of Descartes-08 on patients measured by MG assessments.
Previously in the non-randomized phase 1/2a portion of the trial, participants showed at least 1 full class of improvement in MGFA clinical classification and a 50% mean improvement on the Myasthenia Gravis Composite Scale at 3 months post treatment. In terms of safety, it was reported that Descartes-08 was generally well-tolerated and that no cytokine release syndrome or other treatment-related adverse events (AEs) had occurred. The results were reported at the 14th Myasthenia Gravis Foundation of America (MGFA) International Conference on Myasthenia and Related Disorders, held in Miami, Florida, May 10-12, 2022.2
“We are excited to begin this RCT in patients with MG,” Miloš Miljković, MD, chief medical Officer, Cartesian Therapeutics, noted in the statement.1 “A placebo-controlled design will provide a stringent evaluation of Descartes-08 efficacy while elucidating its mechanisms of action. This will result in important insights on treating MG and other autoantibody-mediated autoimmune diseases with Descartes-08.”