VRDN-001, a Novel IGF-1R Monoclonal Antibody for the Treatment of Thyroid Eye Disease (TED): a Proposed Adaptive Design for Exploratory Proof of Concept

Adaptive design of clinical trials allows for more efficiency and less subject burden than conventional trials in the exploration of effectiveness and safety of drugs. An adaptive strategy is a scheme that allows for prospectively planned modifications to one or more aspects of the design based on accumulated data from subjects within the trial as it is ongoing. Adaptation is planned before comparative analyses of trial data are conducted, allowing opportunities for modifications to the trial itself. VRDN-001 is a humanized IgG1κ monoclonal antibody that binds specifically and with high affinity to human insulin-like growth factor-1 receptor (IGF-1R) and inhibits receptor activation.VRDN-001 is a humanized IgG1κ monoclonal antibody that binds specifically and with high affinity to human insulin-like growth factor-1 receptor (IGF- 1R) and inhibits receptor activation.

Poster 334 VRDN-001, a Novel IGF-1R Monoclonal Antibody for the Treatment of Thyroid Eye Disease (TED): a Proposed Adaptive Design for Exploratory Proof of Concept Denis O'Shaughnessy1, Elisabeth Coart2, Barrett Katz1 1 Viridian Therapueutics, Waltham, Massachusetts, USA, 2International Drug Development Institute, Brussels, Belgium Introduction: Adaptive design of clinical trials allows for more efficiency and less subject burden than conventional trials in the exploration of effectiveness and safety of drugs. An adaptive strategy is a scheme that allows for prospectively planned modifications to one or more aspects of the design based on accumulated data from subjects within the trial as it is ongoing. Adaptation is planned before comparative analyses of trial data are conducted, allowing opportunities for modifications to the trial itself. VRDN-001 is a humanized IgG1κ monoclonal antibody that binds specifically and with high affinity to human insulin-like growth factor-1 receptor (IGF-1R) and inhibits receptor activation.VRDN-001 is a humanized IgG1κ monoclonal antibody that binds specifically and with high affinity to human insulin-like growth factor-1 receptor (IGF1R) and inhibits receptor activation. Methods: Clinical exploration of VRDN-001 will begin with a randomized, placebo-controlled multiple ascending dose (MAD) phase 1/2 trial in healthy volunteers and TED patients and includes multiple measures of efficacy to inform dose selection. If needed, extension cohorts defined after results of the MAD segment allow for further exploration of regimens and dosages. Following this phase 1/2 trial and dependent upon data observed, a potential adaptive phase 2/3 trial design would include a placebo arm and multiple drug dosage arms. Results: This adaptive designed trial includes a masked interim analysis in which the least promising dose cohort(s) would be stopped and the trial continued with the placebo arm and selected dose cohorts, thus protecting statistical validity. Conclusions: Adaptive designs provides a variety of advantages over non-adaptive designs, arising from their fundamental distinguishing property: allowing the trial to adjust to information not available when the trial began. The nature of the advantages depends on types of adaptations considered and include statistical efficiency, ethical considerations, selection of dosages to be brought forward, and smaller sample size requirements. Our clinical exploration of VRDN-001 makes use of principles of adaptive design as we investigate its safety and efficacy. References: None. Abstract Type: Clinical Trial Keywords: Graves' disease, orbit/ocular pathology, neuro-ophth & systemic disease (eg. MS, MG, thyroid), orbit Financial Disclosures: Employee of Viridian Therapeutics, Inc. Grant Support: None. Contact Information: Barrett Katz, [e-mail] 2022 Annual Meeting Syllabus | 491