SITUATION

George Clinical was contracted by a large biopharmaceutical company to run operations in the APAC region for SONAR, a randomized, multi-country, multicenter, double-blind, parallel, placebo-controlled study of the effects of a selective endothelin-A receptor antagonist on renal outcomes in subjects with type 2 diabetes and nephropathy. George Clinical also provided scientific leadership and managed endpoint adjudication for the trial globally.

This class of drugs had never been tested to the full extent in patients, although in the pre-clinical work it was very promising despite potential risks.¹ In SONAR, researchers were able to minimize the known risk of sodium retention and optimize the efficacy of the drug on patients in two ways. One was a carefully selected drug dose. The second was an Enrichment Design which excluded sensitive patients, selecting patients for a substantial albuminuria reduction and minimal clinical signs of sodium retention.

Enrichment designs where randomization is based on biomarker expression, like in the SONAR trial, can be an efficient way of determining the benefit-risk in the biomarker-positive population. Katherine Tuttle (University of Washington, Seattle, USA) said that SONAR “demonstrates a turning point in trial innovation,” and “succeeded in shifting trial design to match patients with treatment on the basis of safety and response assessments during a pre-randomization enrichment period.”² This innovative approach to clinical trials can help to facilitate future clinical trial conduct leading to smaller and more efficient trials.

As a strong proponent of trial innovation with experience in quickly adapting to complex and fluid operations, George Clinical was the ideal partner for the SONAR trial. As part of the Steering Committee of SONAR, our scientific leaders designed this complex study, and in the APAC region, helped maintain a strategic approach to engage sites, interacted with site personnel and helped minimize patient dropout and low retention. The level of hands-on support that George Clinical’s people are always willing to give was crucial in overcoming the many challenges faced.

CHALLENGES & SOLUTIONS

Challenge:

Complex study design including enrichment phase; less complex competing studies recruiting at the same time.

Solution:

George Clinical’s Scientific Leadership model of operations was critical in overcoming this challenge in the APAC region as our Regional Scientific Leader on this project, Dr Muh Geot Wong, who is also a clinician, engaged sites in discussions around recruitment strategies from a clinical perspective. Although novel trial designs provide unique opportunities to expedite drug development, they require thoughtful planning and implementation. George Clinical met these challenges by ensuring rigorous engagement, communication and collaboration among all involved parties. Our scientific leaders with clinical experience helped sponsors/sites to maintain focus on scientific goals while enhancing patient involvement and recruitment efficiency.

In addition, a high potential program was set up for countries such as South Korea and China to engage sites in a way that signaled their preferential treatment as high recruiters. Specific strategies were devised to engage sites with large subject pools to maximize their recruitment capabilities. Multiple teleconferences with scientific leaders to keep communications flowing were scheduled to ensure that sites in all countries could easily participate at “best possible” times. George Clinical’s team encouragement and good experience sharing among all sites resulted in a successful recruitment strategy.

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