Regulus Therapeutics has concluded enrolment in the second cohort of the Phase Ib multiple ascending dose (MAD) trial of RGLS8429 to treat autosomal dominant polycystic kidney disease (ADPKD).

The placebo-controlled, double-blind study is designed to assess the pharmacokinetics, pharmacodynamics, tolerability, and safety of the miR-17 inhibitor RGLS8429 in adults with ADPKD.

It will assess treatment with RGLS8429 across three different dose levels, including measurement of changes in cyst architecture, height-adjusted total kidney volume, polycystins and overall function of the kidney.

Patients will receive 2mg/kg of RGLS8429 or placebo every other week for three months.

Regulus Therapeutics CEO Jay Hagan said: “I am looking forward to watching this cohort progress through the study as well as sharing topline data from our first cohort in the coming weeks.”

Following a review of complete available cohort 2 safety data, Regulus plans to initiate dosing the third cohort in October this year.

The favourable safety and PK profile of RGLS8429 were demonstrated in the Phase I single ascending dose study with no serious adverse events reported.

Plasma exposure was also found to be linear across the four tested doses and showed similar PK data as the first-generation compound, RGLS4326.

A chronic toxicity study of RGLS8429 carried out in mice for 27 weeks also demonstrated no toxicity at any dose level up to the top dose of 300mg/kg.