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.
