ABSTRACT
Background : Adeno-associated virus (AAV)-mediated gene therapy is being investigated as a treatment for people with hemophilia A (PwHA). Commonly studied AAV serotypes include AAV5, AAV6, and AAV8. Pre-existing immunity against these AAVs restricts patient eligibility yet, published data on AAV seroprevalence and seroconversion rate in PwHA are limited. Aims : To describe design and recruitment methods used for the SAVVY study. This study is designed to characterize AAV antibody prevalence and titers, evaluate changes in antibody titer over time, and examine factors that may influence antibody positivity, titer, and seroconversion. Study design and recruitment methods seek to minimize the need for in-person study interactions during the COVID-19 pandemic. Methods : SAVVY is a patient-centered, decentralized, prospective, observational study involving blood draws at 2 time points. The target sample size of 1,000 PwHA represents approximately 5% of PwHA in the US. SAVVY employs a user-friendly mobile application, provides remote recruitment through e-consent, and uses a network of 1,800+ laboratories throughout the US for biospecimen sample collection. This approach minimizes patient travel, reduces potential exposure to COVID-19, and removes burden from HTC staff to perform study assessments. Recruitment has leveraged various forms of virtual outreach to physicians, HTC staff, and patient advocacy groups;direct-to-patients are being used to create awareness of the study and its scientific aims. See Table 1. Results : First patient enrollment occurred within four months of final protocol;41 patients were enrolled within 2 weeks of activation. At the time of abstract submission, 105 patients had consented to participate. Conclusions : The COVID-19 pandemic disrupted the progress of clinical studies necessary for the advancement of treatments. Adaptability to existing conditions is critical. Careful study design and multi-modal engagement with the hemophilia community can facilitate the conduct of studies, minimize risks associated with COVID-19, and may enhance patient experience and clinical trial recruitment.