RGLS8429 for Polycystic Kidney Disease

No longer recruiting at 21 trial locations

Overseen By Kristen Gillotti

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regulus Therapeutics Inc.

Must not be taking: Tolvaptan

Disqualifiers: Alcoholism, Drug abuse, Kidney transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called RGLS8429 for individuals with polycystic kidney disease (PKD). Researchers aim to determine the safety of RGLS8429 and its effects on specific markers related to PKD and kidney size. Participants will receive either the treatment or a placebo (a harmless pill with no active drug) to compare results. The trial seeks individuals diagnosed with PKD who have undergone a specific type of kidney imaging in the past five years. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken tolvaptan in the 28 days before joining. It's best to discuss your medications with the trial team.

Is there any evidence suggesting that RGLS8429 is likely to be safe for humans?

Research has shown that RGLS8429 has promising safety results from earlier studies. In a study with 26 participants, the treatment was well-tolerated, and no major safety issues emerged.

In lab tests, RGLS8429 improved kidney function and size, indicating positive safety signs. This current trial is in an early stage, focusing on the safety and tolerability of RGLS8429 for people. Early-stage trials involve testing for safety, so researchers closely monitor participants for any side effects.

Overall, existing data suggests RGLS8429 is generally safe, but ongoing trials will provide more detailed information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for polycystic kidney disease, which often include blood pressure medications like ACE inhibitors or ARBs, RGLS8429 offers a novel approach by targeting the genetic underpinnings of the disease. Researchers are excited because RGLS8429 works by modulating microRNAs involved in the disease process, potentially slowing cyst growth and kidney damage. This innovative mechanism of action could provide a more direct and effective way to manage the condition compared to traditional therapies, which primarily address symptoms rather than the root cause.

What evidence suggests that RGLS8429 might be an effective treatment for polycystic kidney disease?

Research shows that RGLS8429, which participants in this trial may receive, may help treat autosomal dominant polycystic kidney disease (ADPKD). Studies have found that this treatment boosts levels of polycystin, a protein important for kidney health. Specifically, researchers observed that RGLS8429 increases certain proteins in urine, which might help reduce kidney size. Early results suggest it could lower the total kidney volume relative to body height, a positive sign for managing ADPKD. Overall, these findings offer hope for improved kidney function in people with this condition. ^{1 3 6 7 8}

Who Is on the Research Team?

Rekha Garg, MD

Principal Investigator

Regulus Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with Autosomal Dominant Polycystic Kidney Disease (ADPKD), specifically those classified as 1C, 1D, or 1E by Mayo Imaging. Participants must have a certain level of kidney function (eGFR between 30 to 90 mL/min/1.73 m2) and a BMI of 18 to 35 kg/m2. They cannot have taken the drug tolvaptan in the last month or be part of another study recently.

Inclusion Criteria

Must understand and consent to the study procedures explained in the ICF and be willing and able to comply with the protocol

You have a certain classification of ADPKD based on an MRI scan taken during screening or within the past 5 years.

Your kidney function, measured by eGFR, needs to be between 30 and 90 mL/min/1.73 m2.

Exclusion Criteria

You have taken tolvaptan within the 28 days before the study starts.

Subject is mentally incapacitated or has significant emotional problems

Any medical condition or social circumstance that, in the opinion of the Investigator, may make the subject unlikely to complete the study or comply with study procedures and requirements; or may pose a risk to the subject's safety

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Multiple ascending doses of RGLS8429 or placebo administered via subcutaneous injection every other week for 7 doses

14 weeks

7 visits (in-person)

Treatment Part B

Fixed-dose of RGLS8429 administered via subcutaneous injection

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• RGLS8429

Trial Overview The trial tests RGLS8429's safety and its effect on ADPKD biomarkers compared to a placebo. It also looks at how it affects kidney size related to height (htTKV), its behavior in the body (pharmacokinetics), and overall kidney function.

How Is the Trial Designed?

Group I: RGLS8429 Experimental Treatment 1 Intervention

The randomized,double blind part of the study (Part A) will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total). * Cohort 1: first dose level of RGLS8429 or placebo * Cohort 2: second dose level of RGLS8429 or placebo * Cohort 3: third dose level of RGLS8429 or placebo

Group II: Placebo Experimental Treatment 1 Intervention

The randomized double blind part of the study (Part A) will consist of three sequential cohorts of approximately 12 subjects each randomized centrally to receive RGLS8429 or placebo by subcutaneous injection every other week (Q2W) x 7 doses (36 subjects total). * Cohort 1: first dose level of RGLS8429 or placebo * Cohort 2: second dose level of RGLS8429 or placebo * Cohort 3: third dose level of RGLS8429 or placebo

Group III: Open Label Fixed Dose RGLS8429 Experimental Treatment 1 Intervention

The open-label fixed dose part of the study (Part B and Cohort 4) will consist of a single cohort of up to 30 subjects each receiving 300 mg RGLS8429.

Who Is Running the Clinical Trial?

Regulus Therapeutics Inc.

Lead Sponsor

Trials

3

Recruited

130+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05521191

NCT05521191 | A Study of RGLS8429 in Patients With ... Primary Objectives. To assess the safety and tolerability of RGLS8429; To assess the impact of RGLS8429 on ADPKD biomarkers. Secondary Objectives.

2. prnewswire.com prnewswire.com/news-releases/regulus-therapeutics-announces-successful-completion-of-its-phase-1b-multiple-ascending-dose-mad-clinical-trial-of-farabursen-rgls8429-for-the-treatment-of-autosomal-dominant-polycystic-kidney-disease-adpkd-302412705.html

Regulus Therapeutics Announces Successful Completion ... Positive Topline Data from the Fourth Cohort of Patients. Consistent demonstration of polycystin (PC) biomarker impact confirming 300 mg ...

3. docwirenews.com docwirenews.com/post/effect-of-rgls8429-on-pc1-pc2-and-httkv-in-adpkd

Effect of RGLS8429 on PC1/PC2 and htTKV in ADPKD RGLS8429 increases urinary PC1 and PC2 and may reduce height-adjusted total kidney volume (htTKV) in patients with ADPKD.

4. ir.regulusrx.com ir.regulusrx.com/2024-01-02-Regulus-Therapeutics-Announces-Completion-of-Enrollment-in-Third-Cohort-of-Phase-1b-Multiple-Ascending-Dose-MAD-Clinical-Trial-of-RGLS8429-for-the-Treatment-of-Patients-with-Autosomal-Dominant-Polycystic-Kidney-Disease-ADPKD

1b - MAD study of RGLS8429 for the treatment of ADPKD. The protocol was amended to include a fourth cohort of subjects who will receive an open label fixed dose of RGLS8429 to compare biomarker and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05429073

NCT05429073 | A Study of RGLS8429 in Healthy Volunteers Individual Patients: Allows a single patient, with a serious disease or condition who cannot participate in a clinical trial, access to a drug or biological ...

6. prnewswire.com prnewswire.com/news-releases/regulus-therapeutics-announces-positive-clinical-and-regulatory-updates-from-its-autosomal-dominant-polycystic-kidney-disease-adpkd-program-for-farabursen-rgls8429-302362731.html

Regulus Therapeutics Announces Positive Clinical and ... ... Polycystic Kidney Disease (ADPKD) Program for Farabursen (RGLS8429) ... In addition, review of complete safety data from all 26 subjects ...

7. mayo.edu mayo.edu/research/clinical-trials/cls-20543555

A Study of RGLS8429 in Patients With Autosomal ... About this study. The purpose of ths study is to assess the safety and tolerability of RGLS8429. Addiitionally, to assess the impact of RGLS8429 on ADPKD ...

8. sec.gov sec.gov/Archives/edgar/data/1505512/000119312525053925/d910609dex991.htm

EX-99.1 Complete safety data from all 26 subjects demonstrated farabursen was ... Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in ...