A multi-center pivotal field study to confirm the effectiveness and safety of verdinexor for the treatment of lymphoma in dogs.

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Project Summary/Abstract: The proposed study will contribute to completing the requirements for our New Animal Drug Application (NADA) effectiveness technical section for the designated intended use. Study Design This will be a prospective, randomized, double-masked, placebo-controlled, multi-site, pivotal field study designed to evaluate verdinexor for the treatment of lymphoma in dogs. Treatment Groups and Number of Animals On study Day 0, study-eligible dogs will be randomized to the IVP or CP treatment group in a 4:1 ratio, in blocks of 5. A single study protocol will be followed at multiple study locations. A sufficient number of dogs will be enrolled in the study across all sites to complete the study with at least 100 evaluable cases treated with verdinexor and 25 evaluable cases treated with placebo tablets. An evaluable sample size of 100 IVP and 25 CP dogs, assuming a median time to progression of 28 days and 7 days respectively, will provide more than 90% power (alpha = 0.05, 2-sided). To be eligible for the statistical analysis, each study site must complete a minimum of 5 evaluable cases, at least 1 per treatment group. No more than 25% of evaluable cases should be enrolled at any one site. A simulation of 10,000 clinical trials, using the statistical model specified for the analysis, was generated to determine if the proposed sample size would have adequate power. Statistical Analysis: Effectiveness Endpoints: Primary Effectiveness Variable The primary effectiveness variable will be time to progression (TTP). TTP is defined as the time from Day 0 to time of progressive disease. A case will be considered to be in progressive disease state if either the definition of progressive disease for target lesions in section 16.8.1.3, OR, if the definition of progressive disease for non-target lesions in section 16.8.2.2, is met. Effectiveness will be established if the median TTP of lymphoma in dogs is statistically significantly longer in the treated group compared to the placebo group. Correlation of the statistical treatment success to the clinical benefit of the drug will be addressed in the Final Study Report (FSR). Safety Assessment Safety will be evaluated based on physical exam, serum chemistry, hematology and urinalysis parameters and the occurrence of adverse events.