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Exceptional kidney and metabolic scientific leadership network provides continuity, communication and cultural expertise in long-term global trial program.
Background
The National Institute of Diabetes and Digestive and Kidney Diseases (NIH) estimates that more than one in seven people with kidney disease have anemia, increasing their chance of developing heart problems and strokes. The prevalence of anemia increases as chronic kidney disease (CKD) progresses and is associated with an increased risk of hospitalization, cardiovascular complications and death. CKD is a significant global burden with more than 700 million people worldwide living with CKD. Current common treatments for CKD anemia include Erythropoiesis-Stimulating Agents (ESAs) and intravenous iron. However, there are safety concerns around both.
In 2011, the FDA began recommending more conservative dosing of ESAs because of data showing increased risks of cardiovascular events. KDIGO guidelines also suggest a conservative use of ESAs and express concern over the use of intravenous iron. These facts indicate the importance of finding new treatments for the millions of patients globally with CKD related anemia.
Hypoxia-inducible factor (HIF) prolyl hydroxylase enzyme inhibitors (PHI) are a new class of agents that could potentially play an important role in the treatment of renal anemia and have shown enough promise in clinical trials to warrant significant attention. HIF-PHIs would avoid injections and may also reduce the tendency to raise blood pressure. Clinical trials are underway to determine if HIF-PHIs are associated with fewer adverse cardiovascular effects at comparable hemoglobin levels.
“This is an exciting time because typically nephrology has been seen as a specialty using traditional treatments not well supported by strong evidence-based practices. That is because most clinical trials exclude patients with kidney disease due to concerns over their risk factors. The ASCEND trials will provide more insights on the safety and efficacy of HIF-PHI in treatment of anemia in CKD. It will also address their role in cardiovascular—even in pre-dialysis and patients receiving dialysis.”
Muh Geot Wong, George Clinical scientific leader, Sydney, Australia and George Clinical ASCEND team member
Situation
ASCEND Program Evaluates HIF-PHI in 41 Countries
GlaxoSmithKline has conducted multiple studies under the Phase III ASCEND program to evaluate the efficacy and safety profile of daprodustat, an investigational HIF-PIH for CKD patients with anemia. The program enrolled more than 8,000 patients in 41 countries who were treated for up to 4.26 years.
ASCEND-D, an event-driven, open label, randomized, active-controlled, parallel-group, multicenter Phase III trial, conducted in 41 countries worldwide, was one of the largest anemia studies in dialysis patients (2964 patients), performed across Europe, North America, Latin America and Asia Pacific.
ASCEND-ND trial randomized 3,872 non-dialysis dependent patients spanning more than 40 countries and evaluated the efficacy and safety of daprodustat when compared with darbepoetin alfa in CKD patients with anemia not requiring dialysis.
In addition to the ASCEND-D and ASCEND-ND studies, the program also included studies focused on incident dialysis for patients just starting dialysis (ASCEND-ID); quality of life measures (ASCEND-NHQ); as well as three-times weekly dosing regimens (ASCEND-TD). Each of the studies from the program met its respective primary or co-primary endpoint(s).
George Clinical was involved in steering committee management for the studies since the beginning of the program which included the major effort of organizing all steering committee meetings for the duration of the program and managing their logistics, members and oversight responsibilities.
Global and national scientific leadership from George Clinical participated across the many countries involved in this enormous program. These committees were led by Zuhaib Baig of project operations as the global project lead with support from several George Clinical operations team members as well as fellow scientific leaders Dr. Muh Geot Wong and Dr. Inna Kolesnyk.
With our more than 20 years of global kidney and metabolic experience and our network of recognized and influential kidney and metabolic scientific leaders, George Clinical was a good fit for the job and was present and accounted for in every “corner” of the ASCEND program.
Challenges
Long-term global trials face challenges including recruitment and retention. And in the case where a long-running trial involves patients with poor health conditions, such as CKD anemia, these issues become even more critical.
ASCEND was a multi-trial, multi-year program spanning more than 40 countries creating many logistical challenges and a high risk of dropouts. In addition, there were language and cultural issues as well as nuances in treatments and clinical practices from country to country and even site to site. Challenges included proper messaging and communications specific to each country/patient population.
It must also be noted that much of the program was conducted during the pandemic, adding further challenges and stresses to all involved.
