Pacibekitug Lowers Inflammatory Markers in Chronic Kidney Disease

TRANQUILITY Trial Tests IL-6 Antibody in Kidney Disease

The Phase II TRANQUILITY trial evaluated pacibekitug, a monoclonal antibody targeting interleukin-6 (IL-6), in patients with stage 3–4 chronic kidney disease (CKD) who had elevated high-sensitivity C-reactive protein (hs-CRP) levels.

A total of 143 participants were enrolled across 49 U.S. centers. Patients were randomized to receive different doses of pacibekitug or placebo over six months, with the primary aim to assess changes in inflammatory biomarkers.

Study Design and Population Details

Participants included adults with CKD stage 3–4 and hs-CRP levels between 2 and less than 15 mg/L. The mean age was 69 years, 64% were women, 72% received statins, and 59% had diabetes.

Pacibekitug was administered as 25 mg or 50 mg every 90 days, or 15 mg every 30 days, compared to placebo. The trial was placebo-controlled and ran for six months.

Key Findings: Reductions in Inflammatory Biomarkers

Pacibekitug treatment led to dose-dependent decreases in hs-CRP by day 30, which were maintained through day 180. Median time-averaged change in hs-CRP was +7% with placebo, −76% with 25 mg every 90 days, −85% with 50 mg every 90 days, and −89% with 15 mg every 30 days (all p < 0.0001 vs. placebo).

Sustained reductions were also observed in other inflammatory markers, as well as fibrinogen and lipoprotein(a), across all pacibekitug groups compared to placebo.

Safety and Tolerability

Pacibekitug was generally well tolerated. Few participants discontinued the drug (1.9%), and no clear dose-related safety signals were identified during the six-month trial.

No new safety concerns were reported in this study population.

Context for Metabolic Health and Remaining Questions

Inflammation is increasingly recognized as a contributor to cardiovascular risk in people with chronic kidney disease, even when traditional risk factors such as hypertension, diabetes, and high cholesterol are managed.

The study's principal investigator noted that the next step is to determine whether these biomarker changes translate into improved cardiovascular outcomes in larger, longer-term trials.

Limitations and Next Steps

The TRANQUILITY trial measured changes in biomarkers but did not assess clinical outcomes such as heart attack or stroke. The findings apply to patients with stage 3–4 CKD and elevated hs-CRP.

Further research is needed to confirm if lowering inflammatory markers with pacibekitug leads to better cardiovascular health or kidney outcomes over time.