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Article History

Received: 4 February 2025

Accepted: 16 September 2025

First Online: 2 October 2025

Declarations

:

: Denis Barritault is co-inventor and co-owner in the patents describing RGTA® technology and applications. He is the founder, president, and shareholder of the company OTR3, which manufactures and commercializes CACIPLIQ20®. Frederic Sedel, Martin Inizan, Franck Chiappini, and Agnes Choppin are employees and shareholders of OTR3 and are co-inventors of patents describing OTR4132-MD technology and applications. Charlotte Rosso, Catherine Oppenheim, and Francisco Moniche received fees for their work as members of the independent data safety monitoring board. Other authors declare no conflicts of interest in relation with this work.

: The study was approved by the ethics committee (Comité de protection des personnes Ile de France 5) under the reference 21.01365.000016 and by the French regulatory authority (Agence nationale de sécurité du médicament et des produits de santé) under the reference DMCDIV/FLOW/AE/2018-A03117-48-B/MS2. The study was performed in accordance with the standards of ethics outlined in the Declaration of Helsinki.

: Written informed consent followed an emergency procedure with three different possibilities: (1) direct patient informed consent when the patient was conscious and able to provide its consent, (2) legal representative if the patient was not able to provide their consent, and (3) an independent physician (not investigator in the study) when the patient was not able to provide their consent and when there was no legal representative available. In cases (2) and (3), patient’s written informed consent was obtained afterwards, once the patient recovered sufficiently, in order to continue the study follow-up and to authorize the use of study data.

: Not applicable.

: Not applicable.

: Study data are available on request to the sponsor OTR3.

: All authors contributed to this work and provided feedback on the drafting of the manuscript. Olivier Detante, Frederic Sedel, Martin Inizan, and Denis Barritault were involved in the design of the clinical trial. Olivier Detante, Xavier Barreau, René Anxionnat, Olivier Heck, and Igor Sibon were investigators in the study and participated in the collection and analysis of the data. Charlotte Rosso, Catherine Oppenheim, and Francisco Moniche were members of the data safety monitoring board and were involved in data interpretation, dose escalation, methodological aspects, revising the manuscript for important intellectual content, and final approval of the version to be published. Franck Chiappini and Agnès Choppin were involved in the preclinical phases, data analysis and representation, funding, and submission to regulatory authorities. All authors read and approved the final version.