Research gives insight for improving future lupus clinical trials
A new study that analyzed lupus treatment data from past global clinical trials suggests that when testing new drugs in combination with other background therapies, clinical trials should be designed to account for the effects that initial disease activity and background drug treatment have been shown to have on planned endpoints, like response and flare rates. The analysis was conducted by the Lupus Foundation of America to improve the design of future lupus clinical trials in order to secure a full arsenal of new treatments for lupus, an unpredictable and potentially fatal disease that affects millions of people worldwide.
The data was presented at the American College of Rhematology Annual Scientific Meeting in San Diego by Dr. Kenneth Kalunian, associate director of the Center for Innovative Therapy (CIT) at the University of California San Diego. Dr. Kalunian chairs the Lupus Foundation of America’s Collective Data Analysis Initiative (CDAI). In 2011 this initiative formed the Standard of Care in Clinical Investigational Trials Program (SOCCIT) to better understand the effect of standard of care treatments in lupus clinical trials.
An earlier analysis of the SOCCIT program, presented by Dr. Kalunian in 2011, revealed that the background drug mycophenolate mofetil (MMF) was associated with improvement in health status. This new analysis, however, shows that participants on MMF entered the trial with higher measures of baseline disease activity. Individuals with higher baseline scores were more likely to experience flares during the trial, possibly because they were sicker when entering the trial. This may confound trial results and make it more difficult to prove that a potential new treatment for lupus is effective.
Additional data analysis will provide further insight that may help future lupus clinical trial sponsors determine which patients to included in a study, the specific endpoints to be measured, and which background medications will provide a more reliable and accurate evaluation of the investigational drug’s effectiveness.
For this new study, investigators used data obtained from six multicenter phase 2 or phase 3 lupus clinical trials involving 933 individuals with systemic lupus, who were receiving standard-of-care (SOC) but no investigational agents. The analysis revealed that, as a group, people with lupus who entered clinical trials on the background drug mycophenolate mofetil (MMF) tended to have more flares overall (an increase in lupus disease activity) and more severe flares, than participants who were on other standard-of-care therapies. The analysis also showed that participants on MMF had greater disease activity scores when they entered the study, suggesting that treatment with MMF might define a sicker subset of patients.
In the past two decades, more than a dozen lupus investigational drugs have failed to meet their endpoints despite promising evidence from earlier studies in animal models and smaller trials involving humans. In response, the Foundation launched the Lupus Foundation of America Collective Data Analysis Initiative (LFA-CDAI), the first study to examine the effects of background therapies on the results of lupus clinical trials.
"Sponsors of trials to test the effectiveness of potential new treatments for lupus, need to take into consideration the effects MMF and other background therapies may have on the results and factor that impact into the planned endpoints, based on the demonstrated effects of MMF on response and flare rates,” said Ken Kalunian, MD.
The SOCCIT Program represents an important step in removing barriers to obtain approval of new, more tolerable and effective lupus treatments. Future analysis will look at other background therapies as well as their impact on specific organs.