The challenge of patient recruitment into early phase clinical trials: Is time-effective academic translational research feasible? Lessons from a phase I/II trial in patients with B-cell deficiencies.

Recruiting patients in early-phase clinical trials poses significant challenges, particularly when targeting specific patient populations. This emerged during the phase I/II B-pVAC-SARS-CoV-2 trial investigating CoVac-1, a peptide-based T-cell activator developed to provide T-cell-mediated protection against severe COVID-19 in individuals with inherited or acquired B-cell deficiencies who were unable to mount adequate antibody responses following approved vaccination AGAINST SARS-CoV-2. Despite promising phase I results in healthy volunteers and high patient interest, recruitment of immunocompromised subjects proved substantially more difficult than initially anticipated. Strict inclusion and exclusion criteria, combined with the complexity of patient profiles, required assessing 1,024 candidates at one site to finally recruit 61 subjects and extended the recruitment process to over 8 months. Our experience highlights how rigid eligibility criteria and lengthy protocol adaptation processes may unintentionally limit access to promising investigational treatments for patients with urgent unmet medical needs. More flexible, patient-tailored approaches, whenever safety is not compromised, together with more pragmatic approaches to protocol adaptation, for instance driven by expedited consultations with the DSMB, may help improve recruitment, while preserving patient safety and trial integrity, particularly in academic early-phase clinical research.