An open-label study for participants who are non-responders at the end of treatment assessment on the VRDN-001-101 and VRDN-001-301 pivotal studies

This open-label follow-on study is intended for participants identified as non-responders at the end-of-treatment assessment in the pivotal VRDN-001-101 and VRDN-001-301 trials. The program is designed to give these participants continued access to investigational treatment and to systematically collect safety and response data in a real-world, uncontrolled setting. As an open-label protocol, both investigators and participants will be aware of treatment assignments, enabling close monitoring and comprehensive adverse event reporting while allowing investigators to evaluate clinical outcomes without the constraints of blinding.

The study focuses specifically on the subset of individuals who did not meet pre-specified response criteria at the conclusion of their participation in the parent pivotal studies, ensuring that data gathered are directly relevant to this clinically important group. Primary objectives center on characterizing safety and tolerability of continued exposure to the investigational agent in participants who lacked an adequate response previously; secondary objectives emphasize additional measures of clinical activity, durability of any subsequent responses, and exploratory assessments that may inform future development decisions. Enrollment is limited to those meeting the non-responder definition at their end-of-treatment assessment in VRDN-001-101 or VRDN-001-301, preserving continuity of care and enabling longitudinal follow-up. Study procedures prioritize systematic collection of adverse events, concomitant medications, and relevant clinical assessments already used in the pivotal studies to allow consistent comparisons and aggregation of safety and effectiveness signals. Ethical considerations include ensuring informed consent for continued investigational treatment, clear communication of the open-label nature of the study, and provision for appropriate clinical oversight given the prior non-response status of participants.

Data derived from this open-label cohort will be valuable for understanding the safety profile of extended treatment exposure, for evaluating whether additional treatment can lead to delayed responses in a subset of prior non-responders, and for informing design elements of subsequent trials or labeling discussions. Although uncontrolled, the study's focused population and consistent assessment schedule relative to the parent trials support meaningful interpretation of results in the context of the overall development program. The study is positioned as a pragmatic step within the VRDN-001 development pathway to address the clinical question of how to manage participants who do not achieve response by the end of the pivotal treatment period, offering both potential clinical benefit to those participants and important programmatic data to sponsors and investigators.

Oversight mechanisms, including investigator assessment and safety monitoring, are integral to the protocol to protect participants and ensure data quality. Findings from this open-label study will complement the randomized pivotal data by providing additional insight into extended exposure, safety signals, and the possibility of late-onset efficacy in a defined non-responder population from VRDN-001-101 and VRDN-001-301.