Patients in the fourth cohort will receive an open label fixed dose of 300 mg of RGLS8429 every other week for three months. The study protocol has been amended to include up to 30 subjects in the fourth cohort in order to further examine potential impact on total kidney volume in patients with APDKD.
"After sharing positive topline data from cohort 2 that further validates RGLS8429's potential efficacy in ADPKD, we are moving to the fourth and final cohort of the Phase 1b MAD study," said Jay Hagan, CEO of Regulus Therapeutics. "This open label, fixed dose cohort will provide essential insight and data as we begin to think about study design for our potentially pivotal Phase 2 trial. Our team is looking forward to sharing further updates as they become available, including topline data from the third cohort in the middle of this year."
The Phase 1b MAD study is a double-blind, placebo-controlled trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD) of RGLS8429 in adult patients with ADPKD. The study will evaluate RGLS8429 treatment across three different weight-based dose levels, including measuring changes in urinary polycystins PC1 and PC2, height-adjusted total kidney volume (htTKV), cyst architecture, and overall kidney function. PC1 and PC2 are the protein products of the PKD1 and PKD2 genes respectively and have been shown to inversely correlate with disease severity. The Company amended the protocol to include a fourth cohort of up to 30 subjects who will receive a fixed dose of 300 mg of RGLS8429 administered every other week for three months.
About ADPKD:
Autosomal Dominant Polycystic Kidney Disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes, is among the most common human monogenic disorders and a leading cause of end-stage renal disease. The disease is characterized by the development of multiple fluid filled cysts primarily in the kidneys, and to a lesser extent in the liver and other organs. Excessive kidney cyst cell proliferation, a central pathological feature, ultimately leads to end-stage renal disease in approximately 50% of ADPKD patients by age 60. Approximately 160,000 individuals are diagnosed with the disease in the United States alone, with an estimated global prevalence of 4 to 7 million.
About RGLS8429:
RGLS8429 is a novel, next generation oligonucleotide for the treatment of ADPKD designed to inhibit miR-17 and to preferentially target the kidney. Administration of RGLS8429 has shown clear improvements in kidney function, size, and other measures of disease severity in preclinical models. Regulus announced completion of the Phase 1 SAD study in September 2022. The Phase 1 SAD study demonstrated that RGLS8429 has a favorable safety and PK profile. RGLS8429 was well-tolerated with no serious adverse events reported and plasma exposure was approximately linear across the four doses tested. In the Phase 1b MAD study Regulus announced both topline data from the first cohort of patients in September 2023 and from the second cohort of patients in March 2024. Regulus announced completion of enrollment in the third cohort in January 2024 with patients receiving 3 mg/kg of RGLS8429 or placebo every other week for three months. Topline data from the third cohort is anticipated in mid-2024.
