A double-blind, randomized, placebo-controlled with an open-label rollover extension phase 2/3 clinical trial to evaluate safety and efficacy of us-APR2020 in subjects with CKD stage IV

Background: CKD patients experience poor quality of life due to high levels of uremic toxins in the blood. Renadyl™, a Pro/Prebiotic dietary supplement has been in the market since 2010. It is proven to reduce several uremic toxins in 3 pilot clinical trials with no adverse outcomes. The product is now awaiting FDA‐IND approval for a drug trial. This will be a large scale 12‐month RCT to validate US‐APR2020 as a Live Bio‐ Therapeutic drug product (LBP) under CBER guidelines. Methods: (A) 6‐month randomized placebo‐controlled parallel design in an outpatient setting followed by (B) 6 month Open‐Label Rollover Extension which will enroll all patients from study A. Results: Study end points: As compared to placebo; Primary: 1: Less than 10% adverse event in the study population. 2: Arrest the decline of eGFR as per NKF‐USFDA guidelines. Secondary: 1: Improvement in any of the basic blood uremic metabolic markers. 2: Improvement in any of the complete blood count (CBC) and hematology parameters. 3: Reduction in C‐Reactive Protein (CRP) levels. 4: Percent change from baseline in rating scale (Modified SF36 QOL questionnaire) at the end of 6 and 12 month. Tertiary (IN FEW SELECTED SITES): Blood levels of Kidney Injury Molecule (Kim‐1), Neutrophil Gelatinase‐associated Lipocalin (NGAL), gut microbiome derived uremic toxins: Indoxyl Sulfate (IS), para‐cresyl sulfate (pCS) and Trimethylamine‐N‐Oxide (TMAO). Conclusions: This is the first‐ever clinical trial proposed using Pre/probiotics USAPR2020 as a Live Bio‐Therapeutic drug product (LBP) for CKD IV patients. Being noninvasive the intervention avoids any possible infection. The addition of US‐APR2020 with standard care of therapy may possess excellent potential towards CKD applications worldwide. Formal IND process under CBER/US FDA in progress.