Trial design and oversight
SARS-CoV-2 infection, congenital or acquired B-cell deficiency, Cancer
SARS-COV-2 INFECTION, HYPOGAMMAGLOBULINEMIA, FRANKLIN, ONCOLOGY, CANCER
The multi-center Phase I/II trial (ClinicalTrials.gov Identifier: NCT04954469) was conducted at the Clinical Collaboration Unit (CCU) Translational Immunology, University Hospital Tübingen, the Institute of Clinical Cancer Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt and the Department of Hematology, Oncology and Cancer Immunology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany. Men as well as non-pregnant women aged ≥18 years, with congenital or acquired B-cell deficiency, defined by either decreased IgG serum concentration, ongoing immunoglobulin substitution for hypogammaglobulinemia, or ongoing or following (up to six months) treatment regimens containing anti-CD20 immunotherapy (e.g., rituximab) were eligible. Patients were enrolled independently of COVID-19 vaccination status if negative for anti-spike SARS-CoV-2 antibodies at the time of inclusion. Individuals with history of SARS-CoV-2 infection (real-time polymerase chain reaction (PCR) or antibody test) were excluded. A detailed description of inclusion and exclusion criteria is provided in the Supplementary Information. Health status was based on medical history and laboratory values, vital signs and physical examination at screening. With regards to sex and gender of patients, only sex was considered for this trial, which was based on self-reported assessment. Prior to enrollment, all patients provided written informed consent. Only eligible patients were recorded in the electronic case report form (eCRF). As safety and efficacy measure, a run-in Phase I trial was conducted with a follow-up period of 28 days after administration, followed by vaccination of further study patients in Phase II. Assessment of the run-in Phase I included the decision to proceed with a single CoVac-1 administration (detailed description in Supplementary Information). The trial was open-label without a control arm and funded by the Federal Agency of Science, Research and the Arts (BMBF), Germany and the Ministry of Science, Research and the Arts Baden-Württemberg (MWK), Germany. The trial was approved by the local ethics committees under the lead of the Ethics Committee at the University Hospital Tübingen (255/2021AMG1) and the competent authority Paul Ehrlich Institute and performed in accordance with the International Council for Harmonization Good Clinical Practice guidelines.Safety and immunogenicity assessment to proceed to Phase II was performed by an independent data safety monitoring board (DSMB).