How to Prioritize Pediatric Populations in NASH Trials

Children and young adults are increasingly affected by rising rates of liver disease. Discover tips for advancing pediatric NASH clinical trials.

Adults aren’t the only patients affected by the increasing prevalence of liver disease. The number of pediatric patients diagnosed with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is on the rise, yet there are currently no approved therapies to treat NAFLD and NASH in adult or pediatric populations.

The need for pediatric pharmaceuticals and biologics to treat the disease is urgent:

• Estimates project roughly one in 10 children will be afflicted by NAFLD.
• As the disease progresses, about one-third of NAFLD pediatric patients will develop significant liver fibrosis and be at risk of developing of cirrhosis and liver failure.
• If untreated, the disease can progress to end-stage liver disease, requiring liver transplantation before the age of 40.

As therapies for the treatment of NASH in adult patients go this year to the U.S. Food and Drug Administration (FDA) for approval, much work remains for drug developers aiming to advance treatments for pediatric populations. By partnering with a contract research organization (CRO) that understands the challenges of liver disease clinical trials — and the complexities of working with pediatric populations — you can drive your treatment forward.

Reflecting Patient Diversity in NASH Trials

Data from NASH clinical trials within adult populations may support clinical research into treatment for pediatric populations. As drug developers seek approval for new NASH therapeutics, the developers must also prepare related pediatric investigational plans. It is not anticipated that waivers will be granted by the FDA as this is a disease that affects children.

The risk factors for the development of liver disease are similar in children and adults, including variability of prevalence according to race and ethnicity. One review found NAFLD rates differ considerably for children ages 2-19 depending on ethnicity:

• Black: 1.5%
• White: 8.6%
• Asian: 10.2%
• Hispanic: 11.8%

Accordingly, pediatric clinical trials for NASH need to attract a widely representative pool of participants that reflects the real-world embodiment of this disease. Diversity in patient recruitment is achieved by taking a number of vital steps that make trials more accessible and user-friendly to a wider range of patients, including:

• Scheduling evening or weekend appointments, using telemedicine appointments or deploying home health care specialists
• Incorporating wearables and apps into data collection
• Engaging and training ethnically representative community physicians as clinical trial investigators, providing a trusted entity who knows the patients and understands the dynamics of a community
• Staffing sites with diverse teams and ensuring that they are trained in good clinical practices, cultural competence and avoiding unconscious bias

Additional challenges in designing a clinical trial for the pediatric population must also be addressed, including:

• Differences in histological patterns between pediatric and adult NASH
• A lack of clear endpoints
• The current need for a liver biopsy as the gold standard in diagnosis

Advance Your Pediatric NASH Clinical Trial

The FDA has provided considerations for pediatric NASH in its draft industry guidance and plans to provide recommendations on pediatric NASH drug development in the future.

Partnership with an experienced CRO is essential to your trial’s success. At the PPD clinical research business of Thermo Fisher Scientific, we have wide-ranging, global experience with NASH studies, including 25 ongoing or completed NASH studies in the past five years. Our experienced team of NASH medical and operational leaders are committed to your study’s success.

Among the capabilities that enable us to drive success in pediatric trials is our Rare Disease and Pediatrics Center of Excellence, comprising more than 20 subject matter experts who work across all therapeutic areas. The Pediatric Core Group sits within the Rare Disease and Pediatrics Center of Excellence and includes experts with in-depth knowledge of:

• Protocol development
• Feasibility
• Study design and study-related issues based on knowledge of current standard of care
• Regulatory trends in the pediatric space

Additionally, our Pediatric Investigator Network encompasses 46 hospitals, four therapeutically aligned networks, and 14 pediatric academic centers of excellence established to speed and optimize the development of therapies for pediatric populations. The network provides access to key opinion leaders and the geographic footprint to support enrollment across the spectrum of therapeutic areas.

In all, global pediatric expertise across PPD includes 17 board-certified pediatricians, more than 2,200 clinical research associates (CRAs) with pediatric experience, and over 500 members of the project delivery team with pediatric experience. In the past five years, we’ve participated in more than 240 pediatric studies across 95 countries that have enrolled more than 92,600 global pediatric patients. We are poised to use our expertise to advance your treatment.

Additional capabilities your CRO should have to contribute to the success of your pediatric trials include:

• Multidisciplinary teams with first-hand knowledge of consent/assent, recruitment, and retention challenges and proven strategies to mitigate risk
• Collaborative relationships with sites to determine the appropriate regulatory structures and processes and access to investigators with relevant pediatric expertise
• Experience in pediatric regulatory activities that enables the development and execution of global strategies, dossier preparation and pediatric investigational plans
• Strong internal study teams that maintain continuity of operations during your study
• A Patient Diversity Team dedicated to guiding study teams in the optimization of trial design and startup, enrollment, and retention of diverse populations
• A commitment to improving engagement with underserved patients, and increasing patient diversity through mobile sites and home visits
• Wide expertise with digital and decentralized solutions to enhance the study experience for both sites and patients, and improve patient recruitment and retention

For liver disease patients of every age, clinical trials are vital to addressing the quality of life and life expectancy.

With broad-ranging experience operating clinical trials for NAFLD/NASH patients, and an extensive, proven network of resources devoted to the care and treatment of pediatric patients, the PPD clinical research business of Thermo Fisher Scientific is positioned to enable you to create effective, safe and valuable new therapies for pediatric NASH patients.