Volenrelaxin for Chronic Kidney Disease

No longer recruiting at 36 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must be taking: ACEi, ARB

Disqualifiers: Heart failure, Dialysis, Transplant, Cancer, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and safety of Volenrelaxin for individuals with Chronic Kidney Disease (CKD). Participants will receive varying doses of Volenrelaxin or a placebo to determine the most effective dose. The study will last approximately 24 weeks and seeks adults with CKD who have been on stable treatment and are not experiencing recent heart problems or undergoing dialysis. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

You can continue your current medications if they are stable. You must stay on your ACE inhibitor or ARB and any other CKD or diabetes medications you are already taking.

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

Research has shown that Volenrelaxin is generally safe and well-tolerated. Studies have found that a weekly injection under the skin improves blood flow to the kidneys, which can enhance kidney function.

In earlier studies, participants did not report major side effects from Volenrelaxin. These findings suggest it might be a safe option for those with chronic kidney disease. However, new treatments can affect individuals differently. Participants should discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Chronic Kidney Disease?

Unlike the standard of care for chronic kidney disease, which typically involves medications like ACE inhibitors or ARBs to control blood pressure and slow disease progression, Volenrelaxin offers a novel approach. Volenrelaxin is unique because it is administered subcutaneously and may work by a different mechanism, potentially offering benefits that current treatments do not. Researchers are particularly excited about its ability to target specific pathways involved in kidney function, which could provide a new avenue for treatment. This innovative approach holds promise for improving outcomes for patients with chronic kidney disease.

What evidence suggests that Volenrelaxin might be an effective treatment for Chronic Kidney Disease?

Research has shown that Volenrelaxin can improve kidney function. In earlier studies, it increased blood flow through the kidneys, allowing more blood to reach them. This improvement continued with repeated doses. The hormone relaxin, related to Volenrelaxin, has shown promise in reducing fluid buildup and enhancing kidney performance. These findings suggest that Volenrelaxin might aid individuals with Chronic Kidney Disease by supporting better kidney health. Participants in this trial will receive varying doses of Volenrelaxin or a placebo to evaluate its effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with Chronic Kidney Disease. Specific eligibility details are not provided, but typically participants should meet certain health criteria and may be excluded based on factors that could impact the study's results or their own safety.

Inclusion Criteria

I have been on a stable diabetes treatment for over 3 months.

I have been taking the highest dose I can tolerate of an ACE inhibitor or ARB for the last 90 days.

I have been diagnosed with Chronic Kidney Disease according to KDIGO criteria.

Exclusion Criteria

I have been on dialysis in the last 90 days.

Have HbA1c >8.5% at screening

I have had a heart attack, stroke, or other major heart issues in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Volenrelaxin or placebo subcutaneously for the duration of the study

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Volenrelaxin

Trial Overview The trial is testing Volenrelaxin's effectiveness and safety over a 12-week period against a placebo to see if it can help adults with Chronic Kidney Disease.

How Is the Trial Designed?

Group I: Volenrelaxin Dose 3 Experimental Treatment 1 Intervention

Participants will receive Volenrelaxin SC

Group II: Volenrelaxin Dose 2 Experimental Treatment 1 Intervention

Participants will receive Volenrelaxin SC

Group III: Volenrelaxin Dose 1 Experimental Treatment 1 Intervention

Participants will receive Volenrelaxin subcutaneously (SC)

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive Placebo SC

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown promise in managing chronic kidney disease (CKD) by addressing both kidney and heart health, representing a significant advancement in treatment options beyond traditional therapies.

The review also highlights the potential of novel non-steroidal mineralocorticoid receptor antagonists as a new strategy for improving cardiorenal health in patients with diabetic kidney disease, suggesting a shift in CKD management towards more comprehensive approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging pillars of chronic kidney disease: no longer a bystander in metabolic medicine. Wonnacott, A.[2023]

Apararenone (MT-3995) significantly reduced urine albumin to creatine ratio (UACR) in patients with stage 2 diabetic nephropathy, with reductions of 62.9%, 50.8%, and 46.5% for doses of 2.5 mg, 5 mg, and 10 mg respectively, compared to a 113.7% increase in the placebo group after 24 weeks.

The treatment was found to be safe and well-tolerated over 52 weeks, with no clinically significant changes in estimated glomerular filtration rate (eGFR) or serum potassium, despite a slight increase in adverse events with higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apararenone in patients with diabetic nephropathy: results of a randomized, double-blind, placebo-controlled phase 2 dose-response study and open-label extension study. Wada, T., Inagaki, M., Yoshinari, T., et al.[2021]

Blocking the renin-angiotensin-aldosterone (RAAS) system with ACE inhibitors or ARBs is effective in reducing proteinuria and slowing the progression of chronic kidney disease (CKD), but many patients still experience aldosterone breakthrough, which can occur in up to 50% of CKD patients.

Adding aldosterone antagonists like spironolactone or eplerenone to RAAS blockers can further reduce proteinuria, although they may increase the risk of hyperkalemia; newer potassium binders and nonsteroidal MR blockers may help mitigate these risks and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mineralcorticoid receptor blockers in chronic kidney disease. Erraez, S., López-Mesa, M., Gómez-Fernández, P.[2022]

In a study of 599 patients with hypertension and type 2 diabetes, adding aliskiren to losartan treatment significantly reduced urinary albumin-to-creatinine ratios by 20%, indicating improved kidney function.

Aliskiren's renoprotective effects appear to be independent of its ability to lower blood pressure, as the difference in blood pressure between the aliskiren and placebo groups was minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aliskiren combined with losartan in type 2 diabetes and nephropathy. Parving, HH., Persson, F., Lewis, JB., et al.[2022]

Finerenone, a new selective nonsteroidal mineralocorticoid receptor antagonist, has been shown to significantly reduce adverse kidney and cardiovascular outcomes in adults with chronic kidney disease and Type II diabetes, based on randomized controlled trials.

While the incidence of hyperkalemia was higher in patients taking Finerenone compared to placebo, it was lower than that seen with older MRAs like spironolactone and eplerenone, and other adverse effects were similar between groups, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Finerenone: A Novel Third-Generation Mineralocorticoid Receptor Antagonist. Gudino Flores, P., Rodriguez Salazar, JD., Nahar, BL., et al.[2023]

In a study involving 45 patients with chronic kidney disease (CKD), moderate dietary sodium restriction significantly reduced residual albuminuria, indicating improved kidney function during treatment with ramipril.

The vitamin D receptor activator paricalcitol (PARI) showed a small and nonsignificant additional effect on reducing albuminuria when combined with a low-sodium diet, suggesting that dietary changes may be more impactful than PARI in managing albuminuria in CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial. Keyzer, CA., van Breda, GF., Vervloet, MG., et al.[2018]

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as empagliflozin, canagliflozin, and dapagliflozin, have shown significant effectiveness in reducing risks associated with diabetic kidney disease (DKD), including albuminuria and progression to more severe kidney issues, based on recent clinical trials.

Finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA), has been found to effectively reduce kidney-related complications in DKD patients without causing severe hyperkalemia, making it a safer alternative compared to traditional MRAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Narrative Review of Diabetic Kidney Disease: Previous and Current Evidence-Based Therapeutic Approaches. Mima, A.[2022]

For patients with type 2 diabetes and chronic kidney disease (CKD), first-line treatments include metformin and sodium-glucose cotransporter-2 inhibitors, which help manage blood sugar levels and reduce cardiovascular risks.

Renin-angiotensin-aldosterone system inhibitors are highly recommended for patients with diabetes and hypertension, while newer non-steroidal mineralocorticoid receptor antagonists are being evaluated for their safety and effectiveness in diabetic kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes in chronic kidney disease. Triozzi, JL., Parker Gregg, L., Virani, SS., et al.[2021]

Blocking the renin-angiotensin-aldosterone system with ACE inhibitors or ARBs is effective in reducing proteinuria and slowing the progression of chronic kidney disease (CKD), but many patients still experience aldosterone breakthrough, which can occur in up to 50% of CKD patients.

Adding aldosterone antagonists like spironolactone or eplerenone to ACEi or ARB treatment can further reduce proteinuria, although they may increase the risk of hyperkalemia; newer potassium binders and nonsteroidal MR blockers may help mitigate these risks while providing additional cardiovascular and renal benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Mineralcorticoid receptor blockers in chronic kidney disease]. Erraez, S., López-Mesa, M., Gómez-Fernández, P.[2022]

In a study of 18 type 2 diabetic patients with diabetic nephropathy, adding candesartan to their existing antihypertensive treatment led to a significant 25% reduction in albuminuria, indicating improved kidney function.

The dual blockade of the renin-angiotensin system also resulted in a 10 mmHg decrease in systolic blood pressure, demonstrating its efficacy in patients who were not adequately controlled with standard ACE inhibitor therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study. Rossing, K., Christensen, PK., Jensen, BR., et al.[2019]

A new composite biomarker, developed using machine-learning techniques from a large observational study (PROVALID), can help identify which patients with diabetic kidney disease (DKD) will benefit from additional treatments alongside renin angiotensin system inhibitors (RASi).

The effectiveness of the additional treatment is measured by the annual percent change in estimated glomerular filtration rate (ΔeGFR), with higher increases indicating improved prognosis for patients receiving the combination therapy compared to those on RASi alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Candidate composite biomarker to inform drug treatments for diabetic kidney disease. Jones, RD., Abebe, S., Distefano, V., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38782726/

Volenrelaxin (LY3540378) increases renal plasma flow Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney ...

2. academic.oup.com academic.oup.com/ndt/article/40/1/109/7680605

Volenrelaxin (LY3540378) increases renal plasma flow Volenrelaxin showed a sustained improvement in kidney perfusion upon repeated dosing, supporting further clinical development in chronic kidney ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06598631

NCT06598631 | Efficacy and Safety of Volenrelaxin in ... The main purpose of this study is to investigate the efficacy and safety of Volenrelaxin in adults with Chronic Kidney Disease. The study will last about 24 ...

4. ctv.veeva.com ctv.veeva.com/study/efficacy-and-safety-of-volenrelaxin-in-adults-with-chronic-kidney-disease

Efficacy and Safety of Volenrelaxin in Adults With Chronic ... The main purpose of this study is to investigate the efficacy and safety of Volenrelaxin in adults with Chronic Kidney Disease.

5. nature.com nature.com/articles/s41591-025-03939-6

Effects of volenrelaxin in worsening heart failure with ... Relaxin is a peptide hormone that may decrease circulatory congestion and improve kidney function. In this study, we conducted a ...