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Suceena Alexander, MD, joins Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, to discuss platform trial design in IgA nephropathy and beyond.
Hosts Brendon Neuen, MBBS, PhD, and Shikha Wadhwani, MD, MS, sat down with Suceena Alexander, MD, at the inaugural International Society of Glomerular Diseases (ISGD) Clinical Trials Summit in Galveston, Texas.
Alexander, a nephrologist and clinical trialist at Christian Medical College Vellore in India, previewed her summit session, “Platform Trials in GD.” The conversation covered how she built an investigator-initiated IgA nephropathy platform trial in India and where the design could fit across other glomerular diseases.
Alexander traced the trial’s origins to a 2015 India Alliance early career fellowship, which allowed her team to establish a longitudinal IgA nephropathy cohort. The cohort revealed poor outcomes among patients in India. It also showed new therapies were often inaccessible to Indian patients, even after reaching market in the US and Europe. A later senior fellowship under the India Alliance funded the platform trial designed to address these gaps.
00:01 - Welcome from the ISGD Clinical Trials Summit
01:55 - How the Indian IgA nephropathy platform trial began
03:26 - Platform trials vs standard 2-arm trials
05:26 - Building academic trial infrastructure in India
09:18 - Enrollment progress and treatment arms
12:38 - Where platform trials face challenges
13:44 - Lupus nephritis, membranous nephropathy, and C3G
16:51 - What comes next for the trial
Her introduction to platform design came during the COVID-19 pandemic, when multiple therapies were tested under a single protocol. The trial ultimately evolved from a 2-arm design into a platform structure.
“With a platform trial you will be able to compare many arms against a shared control as opposed to a 2-arm trial, and we found [it] to be more efficient and more equitable for participants,” Alexander explained.
Wadhwani noted the appeal for patients. A conventional trial typically carries a 50% chance of receiving the control. When 3 or 4 therapies share a single control arm, the odds of receiving an active intervention rise substantially. Neuen added shared infrastructure as a second advantage, since costs drop once the platform is established.
Because the trial is academic and publicly funded, Alexander’s team lacked the infrastructure available to industry sponsors. They built an in-house dashboard for site monitoring and telemonitoring. Distance poses a major barrier for many patients in India, so the protocol makes alternate follow-up visits remote. Data management relies on institutionally licensed software rather than costly industry platforms, with randomization built directly into the system.
Christian Medical College Vellore serves as the chief center for 11 academic sites across India. The central team holds monthly online meetings with each site’s principal investigators, subinvestigators, and coordinators, and conducts in-person audits every 3 to 4 months. Many participating hospitals still rely on paper records, so sites upload original biopsy, 24-hour urine protein, and creatinine reports as PDFs for source verification.
The trial aims to randomize 585 patients in a 1:1 ratio across 5 arms.¹ Alexander’s team presented data on approximately 283 patients at the World Congress of Nephrology in April, and recruitment has now reached 70%.
All participants receive optimized renin-angiotensin system blockade and a steady dose of dapagliflozin after a 12-week run-in period. One arm continues as control. The 4 intervention arms add low-dose tapering prednisolone, gut-directed budesonide, mycophenolate mofetil tapered at 12 months and stopped at 18 months, or hydroxychloroquine for 2 years.¹,² The primary outcome is the difference in eGFR slope at 2 years, with an interim urine protein-to-creatinine ratio analysis at 9 to 12 months.
Wadhwani emphasized the global relevance. Newer IgA nephropathy therapies reach only a small fraction of patients worldwide, and approval does not guarantee access. Most of the world still relies on traditional therapies, making comparative data on these agents essential.
Neuen pointed out platform trials are not monolithic, citing the CAPTIVATE design for combination therapy as one alternative. Alexander identified unapproved phase 3 agents as a key challenge, since industry requires firewalled data and building those firewalls demands additional infrastructure. Recently approved agents are a better fit.
“You will then get a head-to-head comparison of the approved therapy versus the affordable generics versus control,” she said, adding this approach still requires industry partnership with academic institutions.
Alexander highlighted lupus nephritis as a strong candidate. Belimumab, obinutuzumab, and voclosporin were each tested against a common control, yet no head-to-head comparison exists, and factorial elements could address combinations and steroid minimization. Membranous nephropathy offers a biomarker capable of signaling immunologic remission ahead of clinical remission, which could support first-stage screening. Ultra-rare diseases such as C3 glomerulopathy are also well suited. Alexander noted the VALIANT and APPEAR-C3G programs were run by separate sponsors with separate control arms, when a shared control could have served both.
Podocytopathies may fit less well because of the lack of a validated surrogate. Alexander referenced the DUPLEX trial, in which sparsentan improved proteinuria without a significant eGFR slope benefit.³
Looking ahead, Alexander disclosed her team has secured in-principle funding for a second phase, expected to begin after current recruitment closes, to test combinations of affordable generics.
Editors’ note: Disclosures for Neuen include AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and others. Disclosures for Wadhwani include Boehringer Ingelheim, Calliditas Therapeutics, GSK, Otsuka Pharmaceutical Co., Travere Therapeutics, and others. Alexander reports no relevant disclosures.
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