From The Editor | June 16, 2017

Lupus Research Alliance Enhances Clinical Trials for Patients

Source: Clinical Leader
Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Lupus Research Alliance Enhances Clinical Trials for Patients

The Lupus Research Alliance is the largest non-profit health organization raising money for research into the cause, cure, treatment, and prevention of Lupus and its complications. The research programs funded are typically collaborations with hospitals, medical schools and universities, as well as pharmaceutical companies from around the world.

“Lupus is both an inflammatory and an autoimmune disorder,” says Kenneth M. Farber, CEO & President Lupus Research Alliance. “With this disease, almost any organ system within the body can become inflamed, and that will often result in serious damage. The organs most frequently impacted are the kidneys, the heart, and the brain. There are also skin implications and the condition can impact pregnancy. We know that 90 percent of the patients who have Lupus are women, and that it seems to impact African American women at a dramatically higher rate.”

While treatments are available, Farber notes they are far from perfect. Some of the most common treatments are steroids, antimalarials like plaquenil, and treatments that suppress the immune system. Some chemotherapy treatments are also used. The most common treatment tends to be Prednisone. 

The good news is the treatments often work. The bad news is that they can cause severe side effects in patients. For example, patients taking Prednisone for long periods of time may experience osteoporosis and orthopedic disorders, while those who receive chemotherapy can be at greater risk for a variety of infections.

The Search For Possible Treatments

About three years ago, Lupus Research Alliance decided if it was going to have an impact on patients with Lupus, it would need to ramp up and get more aggressive with its efforts. Prior to that, it primarily funded research grants to investigators at academic institutions. While proud of that work, it was clear developing new therapies in a reasonable amount of time would necessitate new approaches.

“The first thing we did was try to identify the obstacles to developing new therapies for Lupus,” explains Farber. “There has been only one new treatment for Lupus approved by FDA in the last 75 years, and we felt one solution might be to reposition therapies that were already available for other indications. We decided to apply a screening process to every new drug approved by FDA, for any indication, to check for mechanisms of action that might make them pertinent for Lupus. We took a list of over 3,000 drugs and quickly cut it down to 127 drugs. These were drugs on the market that we felt had a mechanism of action that might make them appropriate for Lupus. An expert panel of rheumatologists, immunologists, other Lupus experts, and patients then selected the 20 or 30 products that appeared to hold the most promise. 

Next, Lupus Research Alliance realized that because many Lupus trials had been so unsuccessful, something would have to be done to “de-risk” the process of testing one of these drugs for Lupus. To make trials more attractive to pharma companies, the organization put together a consortium of Lupus clinical investigators (thus far just in the U.S. and Canada) at the most respected academic medical centers in North America. This initiative, called the Lupus Clinical Investigators Network (LuCIN), right now consists of 58 academic medical centers with access to over 20,000 Lupus patients.  The goal is to be able to go to pharma with these trial-ready investigators and patients that will help them conduct a trial faster, more cost-effectively, and hopefully, more successfully and they were   able to get the attention of pharma.

The first partnership was conducted with Janssen on ustekinumab (Stelara), a drug used for psoriasis and arthritis, indications relative to Lupus. It was scored the highest of all drugs by the review group, and the trial was recently completed with results forthcoming.

An App For Patient Reporting

One of the companies that showed the most interest in going down this path was Pfizer. Pfizer’s EVP and CMO, Freda Lewis-Hall, has been an industry leader in the area of patient centricity and looked at Pfizer’s portfolio of products in development to see if there was a way to make the trials more patient-friendly.

“Lewis-Hall and her colleagues suggested that we work together to develop a smart phone app to be used specifically for patient reported outcomes in clinical trials,” says Farber. “Initially, the goal was not to collect data to support the primary endpoint. Rather, we hoped to determine whether we could collect ancillary data in a way that was patient friendly.”

The app was developed using the Apple ResearchKit platform. With Pfizer’s help, study groups comprised of Lupus patients were put together. Conversations were then conducted with these patients about what was important to them regarding clinical trials. Farber refers to these interactions as an incredible set of sessions. They helped determine that fatigue is very important to these patients, even though it is never an endpoint in Lupus clinical trials.    

“Lupus patients will frequently complain about how fatigued they are,” states Farber. “We decided to start the process of validating our smart phone app using standard measures of fatigue, methods rarely used in Lupus trials. We used two questionnaires to measure levels of fatigue and quality of life. One is called Facit-F (Functional Assessment of Chronic Illness Therapy-Fatigue) and the other is the SF-36 vitality scale. The standard questionnaires are being used in a Pfizer trial just getting underway at 10 consortium sites in the U.S. and Canada.”

Prior to implementing this app, patients would report to a site when mandated by the trial protocol and be handed a paper survey to complete. Often they would be asked to remember how they felt four or eight weeks prior to the visit. By administering the questionnaire daily, it’s believed investigators will be able to collect more accurate and valuable data.

The app will also send patients reminders to complete the survey and enter data. Reminders will continue to be sent until the survey is completed, which takes about 10 minutes. In this trial, no drug is being assessed. Pfizer and Lupus Research Alliance are simply hoping to determine if patients can actually use the app successfully.

“We believe apps like this will eventually revolutionize how clinical trials are done,” says Farber. “In future trials, we will be able to let patients take daily pictures of their skin lesions to see how they are reacting to treatments. Another app, being jointly developed with Horizon, also incorporates a smart watch and uses the Samsung platform. Patients will be reminded to complete the questionnaire via a vibration in the smart watch.”

That is actually an intervention trial in which Horizon will test a time-released version of Prednisone. There is reason to believe this drug could cause patients to awake with less joint stiffness. That trial will also allow researchers to determine if the study drug is allowing patients to sleep better at night and is also being conducted through LuCIN.