TOUR006 for Chronic Kidney Disease

(TRANQUILITY Trial)

Not currently recruiting at 48 trial locations

Overseen By Tourmaline Bio

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Tourmaline Bio, Inc.

Disqualifiers: Active infection, Immunodeficiency, Heart failure, others

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

Compensation: Varies

Number of Visits: 6

Duration: 180 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called TOUR006 (also known as PF-04236921) to determine if it can safely lower a specific blood marker linked to inflammation in people with chronic kidney disease. The trial will evaluate different doses of the treatment administered through a simple injection, with some participants receiving a placebo for comparison. It targets individuals diagnosed with chronic kidney disease who have elevated levels of a marker called hs-CRP in their blood. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in chronic kidney disease treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Researchers are currently conducting studies to determine the safety and tolerability of TOUR006. Early results from these ongoing studies suggest that TOUR006 is generally well-tolerated, with most participants not experiencing severe side effects. However, more information is needed to confirm these findings as the studies progress.

The treatment is being tested at different doses—15 mg, 25 mg, and 50 mg—to assess the body's response to subcutaneous injection. Researchers are focusing on potential negative reactions and how TOUR006 affects the body, particularly in reducing CRP levels, which indicate inflammation.

As a Phase 2 study, researchers are closely monitoring safety. While some information is available, the treatment continues to undergo careful testing to better understand its effects and safety in people. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for chronic kidney disease?

Researchers are excited about TOUR006 for chronic kidney disease because it offers a fresh approach compared to existing treatments like ACE inhibitors and angiotensin receptor blockers. TOUR006 is administered subcutaneously, which can provide a more targeted delivery system than oral medications. Unlike standard treatments that primarily manage symptoms, TOUR006 might work differently by directly addressing the underlying mechanisms of kidney damage. This unique approach could potentially lead to better outcomes for patients with chronic kidney disease.

What evidence suggests that TOUR006 might be an effective treatment for chronic kidney disease?

Research has shown that TOUR006, also known as pacibekitug, may help lower CRP levels in patients. CRP, a marker of inflammation, is often elevated in individuals with chronic kidney disease. Early studies found that TOUR006 can reduce these levels, potentially managing complications related to inflammation in kidney disease. The treatment targets a protein called IL-6, which plays a role in inflammation. By blocking IL-6, TOUR006 could reduce inflammation and improve kidney function. These early findings suggest that TOUR006 might effectively address inflammation, a key issue in chronic kidney disease. ^{1 2 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Tourmaline Bio

Are You a Good Fit for This Trial?

This trial is for adults over 18 with chronic kidney disease who have an eGFR between ≥15 and <60 mL/min/1.73 m2 and elevated hs-CRP levels (≥2.0 mg/L but <15 mg/L). Participants must have received a COVID-19 vaccine at least 30 days prior to screening and agree to follow contraception guidelines.

Inclusion Criteria

I received my COVID-19 vaccine over 30 days ago.

Agreement to comply with contraception and reproduction restrictions

My kidney function is reduced but not severely.

Exclusion Criteria

I have had stomach ulcers or tears in my stomach/intestines.

I have severe heart failure or was hospitalized for it in the last 6 months.

I haven't had diverticulitis, inflammatory bowel disease, or a GI abscess in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous administration of TOUR006 or placebo at specified intervals

180 days

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

185 days

What Are the Treatments Tested in This Trial?

Interventions

• TOUR006

Trial Overview

The study tests TOUR006 at different doses (25 MG, 50 MG, and 15 MG) versus a placebo in patients with chronic kidney disease. It aims to assess the drug's safety, how well it's tolerated, its pharmacokinetics (how it moves through the body), and its ability to lower CRP when given quarterly or monthly by injection.

How Is the Trial Designed?

Group I: TOUR006 - 50 MG Experimental Treatment 1 Intervention

50 mg administered subcutaneously at Day 1 and Day 90 (Placebo administered at 30, 60, 120, and 150 Day timepoints)

Group II: TOUR006 - 25 MG Experimental Treatment 1 Intervention

25 mg administered subcutaneously at Day 1 and Day 90 (Placebo administered at 30, 60, 120, and 150 Day timepoints)

Group III: TOUR006 - 15 MG Experimental Treatment 1 Intervention

15 mg administered subcutaneously at Days 1, 30, 60, 90, 120, and 150

Group IV: Placebo Placebo Group 1 Intervention

Administered subcutaneously at Days 1, 30, 60, 90, 120, and 150

Who Is Running the Clinical Trial?

Tourmaline Bio, Inc.

Lead Sponsor

Trials

2

Recruited

220+

Published Research Related to This Trial

Chronic kidney disease (CKD) affects about 25% of patients with type 2 diabetes, but many common diabetes medications, like metformin and sulfonylureas, have safety concerns or require dose adjustments due to renal impairment.

Newer antidiabetic agents, such as DPP-4 inhibitors and SGLT2 inhibitors, may be better tolerated in CKD, but their efficacy and safety still need further clinical evaluation, especially for those with severe kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic considerations for the treatment of diabetes in patients with chronic kidney disease. Scheen, AJ.[2015]

The National Kidney Foundation's Kidney Early Evaluation Program (KEEP) effectively identifies chronic kidney disease (CKD) in high-risk populations, with 28.7% of the 100,000 participants screened found to have CKD, compared to a lower prevalence of 13.1% reported in the general population.

KEEP's structured screening approach not only detects CKD early but also enhances understanding of kidney disease, supporting public health initiatives aimed at improving outcomes for individuals with diabetes, hypertension, or a family history of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening populations at increased risk of CKD: the Kidney Early Evaluation Program (KEEP) and the public health problem. Vassalotti, JA., Li, S., Chen, SC., et al.[2022]

Chronic kidney disease (CKD) is a significant global health issue that can be detected early through simple blood and urine tests, which is essential for effective management and treatment.

The review highlights various management strategies for CKD, including blood pressure control, glucose management, and novel kidney protective agents, which can significantly improve patient outcomes and reduce the risk of kidney failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the management of chronic kidney disease. Chen, TK., Hoenig, MP., Nitsch, D., et al.[2023]

Recent research suggests that declines in estimated glomerular filtration rate (eGFR) of 30% or 40% and levels of albuminuria could serve as surrogate endpoints for assessing chronic kidney disease progression, but their validity may vary depending on the context.

Integrating multiple renal risk markers into risk algorithms may provide a more accurate prediction of drug effects on kidney health, as these algorithms account for the complex interactions between different markers, though they require further validation before use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surrogate endpoints in clinical trials of chronic kidney disease progression: moving from single to multiple risk marker response scores. Schievink, B., Mol, PG., Lambers Heerspink, HJ.[2015]

In a study of 21 patients with BK nephropathy, leflunomide treatment did not show a significant difference in BK viral clearance between low-level (<40 microg/ml) and high-level (>40 microg/ml) groups, indicating similar efficacy in this aspect.

However, higher leflunomide levels were associated with new toxic effects, including hemolysis and thrombotic microangiopathy, which could lead to graft loss, suggesting that careful monitoring of drug levels is crucial for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher levels of leflunomide are associated with hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients. Leca, N., Muczynski, KA., Jefferson, JA., et al.[2021]

In a review of seven cases of Leflunomide (LEF)-induced interstitial lung disease (ILD) in nephropathy patients, it was found that ILD typically developed after about 2 months of treatment and an average accumulated dose of 1192.5 mg.

The study highlighted a concerning mortality rate of 57.1% among patients, particularly noting that factors such as male sex, younger age, and the presence of fever were associated with increased risk of death.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interstitial lung diseases after leflunomide use in nephropathy: an analysis of reported cases in Chinese literature. Zhang, WX., Zhou, W., Zhang, ZQ., et al.[2021]

Among over 1 million adults with end-stage kidney disease, only 31.1% received at least 12 months of predialysis nephrology care, highlighting a significant gap in care.

Racial and ethnic disparities in receiving predialysis nephrology care persisted from 2005 to 2015, with Black and Hispanic adults consistently having lower odds of receiving this care compared to White adults, indicating a need for national strategies to address these disparities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

National Trends in the Association of Race and Ethnicity With Predialysis Nephrology Care in the United States From 2005 to 2015. Purnell, TS., Bae, S., Luo, X., et al.[2022]

In a study of 90,897 patients starting dialysis in the U.S. from 1995 to 1997, the average serum creatinine level was 8.5 mg/dl, indicating significant renal impairment, with a mean predicted GFR of only 7.1 ml/min/1.73 m2.

A notable 23% of patients began dialysis with a predicted GFR of less than 5 ml/min/1.73 m2, highlighting a concerning trend of late initiation of dialysis, which may affect treatment outcomes and costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. Obrador, GT., Arora, P., Kausz, AT., et al.[2013]

This study will evaluate the efficacy and safety of Tripterygium wilfordii multiglycosides in 20 patients with idiopathic membranous nephropathy over a 6-month period, focusing on its ability to reduce proteinuria and improve kidney function alongside standard treatments.

The primary outcome will measure the decrease in urinary protein levels, while safety will be assessed by monitoring adverse events, ensuring a comprehensive evaluation of both effectiveness and safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tripterygium wilfordii multiglycosides in idiopathic membranous nephropathy: Protocol for an open-label randomized controlled clinical trial. Geng, C., Li, Q., Pu, L., et al.[2022]

In a study of 52 patients with refractory nephrotic syndrome treated for 24 weeks, leflunomide combined with prednisone showed a total efficacy rate of 65.30%, which is comparable to the 57% efficacy rate of cyclophosphamide combined with prednisone.

Both treatment groups experienced significant improvements in urinary protein excretion and serum levels of albumin and cholesterol, with leflunomide showing a favorable safety profile and few adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of leflunomide combined with prednisone in the treatment of refractory nephrotic syndrome. Liu, Y., Qu, X., Chen, W., et al.[2018]

Chronic kidney disease (CKD) affected 4.5% of hospitalized patients in China from 2010 to 2015, showing an increase from 3.7% to 4.7% over this period, indicating a growing public health concern.

The study identified rising trends in diabetic kidney disease and hypertensive nephropathy, particularly among urban residents in northern China, suggesting a need for targeted prevention strategies in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spectrum of chronic kidney disease in China: A national study based on hospitalized patients from 2010 to 2015. Huang, YM., Xu, D., Long, J., et al.[2019]

Early nephrological referral for chronic renal failure (CRF) patients significantly improves their condition at the start of maintenance dialysis, leading to better clinical outcomes, as evidenced by a shorter average hospital stay (4.8 days vs. 29.7 days for late referrals).

Patients referred late to nephrology had worse health indicators, including higher blood pressure and elevated serum levels of waste products, and experienced higher early mortality rates (7.1% vs. 1.6% within 3 months), highlighting the importance of timely nephrological management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits of early nephrological management in chronic renal failure]. Jungers, P., Skhiri, H., Zingraff, J., et al.[2016]

Early nephrological referral for chronic renal failure (CRF) patients significantly improves their condition at the start of maintenance dialysis, leading to better clinical outcomes, as seen in a study of 900 patients over 8 years.

Patients referred late to nephrologists had worse health indicators, longer hospital stays (29.7 days vs. 4.8 days), and higher early mortality rates (7.1% vs. 1.6%), highlighting the importance of timely referrals for better patient management and reduced healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits of early nephrological management of chronic renal failure]. Jungers, P., Skhiri, H., Zingraff, J., et al.[2016]

Patients with advanced chronic kidney disease (CKD) enrolled in Taiwan's pay-for-performance (P4P) program had a significantly lower risk of starting dialysis (subdistribution hazard ratio of 0.845) and reduced all-cause mortality (subdistribution hazard ratio of 0.792) compared to those not enrolled.

The P4P program was found to be cost-effective, providing long-term savings and better resource utilization for advanced CKD patients, with lower CKD-related costs for those who initiated dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic evaluation of a pre-ESRD pay-for-performance programme in advanced chronic kidney disease patients. Hsieh, HM., Lin, MY., Chiu, YW., et al.[2022]

A combination therapy of leflunomide (LEF) and prednisone showed a total efficacy rate of 60% in treating IgA nephropathy with nephrotic syndrome, which is comparable to the 65% efficacy rate of the control group receiving prednisone and MMF.

Both treatment regimens were well tolerated by patients, indicating that LEF is a safe option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the therapeutic effects of leflunomide and mycophenolate mofetil in the treatment of immunoglobulin A nephropathy manifesting with nephrotic syndrome. Liu, XW., Li, DM., Xu, GS., et al.[2019]

Citations

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This study will evaluate the safety, tolerability, pharmacokinetics, and CRP-lowering effect of quarterly and monthly subcutaneous administration of TOUR006 ...

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tourmalinebio.com/wp-content/uploads/2024/10/ASPC-2024-Evaluating-TOUR006-in-Participants-with-Chronic-Kidney-Disease-and-Elevated-Hs-CRP-Rationale-and-Design-of-the-TRANQUILITY-Phase-2-Study.pdf

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TOUR006 is being evaluated in the ongoing TRANQUILITY study to characterize the safety and tolerability, PK, and hs-CRP-lowering effect of TOUR006, and to ...

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pacibekitug (TOUR006) / Pfizer, Tourmaline Bio

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This study will evaluate the safety, tolerability, pharmacokinetics, and CRP-lowering effect of quarterly and monthly subcutaneous administration of TOUR006 ( ...

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synapse.patsnap.com/article/tourmaline-bio-starts-phase-2-trial-of-tour006-for-cardiovascular-diseases

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This trial marks the first patient receiving a dose of TOUR006, a long-acting, fully human, anti-IL-6 monoclonal antibody intended to treat atherosclerotic ...

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ir.tourmalinebio.com

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TRANQUILITY is a multicenter, randomized, double-blind, placebo-controlled Phase 2 trial evaluating pacibekitug in patients with elevated hs-CRP ...

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The objective of this Phase 2 study is to characterize the hs-CRP-lowering effect, safety, tolerability, and PK of TOUR006 in patients with chronic kidney ...