A Study to Evaluate TOUR006 in Patients With Chronic Kidney Disease and Elevated Hs-CRP

Tourmaline Bio, Inc., a Novartis Company143 enrolled

Overview

This study will evaluate the safety, tolerability, pharmacokinetics, and CRP-lowering effect of quarterly and monthly subcutaneous administration of TOUR006 (also known as pacibekitug) in participants with chronic kidney disease and elevated hs-CRP.

Previous clinical studies have suggested that IL-6-driven inflammation plays a key role in the pathogenesis of cardiovascular diseases including atherosclerotic cardiovascular disease (ASCVD) and heart failure. This Phase 2 study will evaluate the safety, tolerability, pharmacokinetics, and CRP-lowering effect of quarterly and monthly subcutaneous administration of TOUR006, a fully human monoclonal antibody against IL-6. TOUR006 binds the IL-6 cytokine and inhibits downstream IL-6 signaling, thereby reducing the pharmacodynamic marker, hs-CRP.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

143

Conditions

Chronic Kidney Diseases Chronic Kidney Insufficiency Chronic Renal Diseases

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥18 years at time of ICF signature. * Serum hs-CRP level ≥2.0 mg/L and \<15 mg/L * Diagnosis of chronic kidney disease, eGFR ≥15 and \<60 mL/min/1.73 m2 or eGFR ≥60 mL/min/1.73m2 and UPCR\>200 mg/g * Received COVID-19 vaccine at least 30 days prior to the Screening visit, per participant verbal attestation. * Agreement to comply with contraception and reproduction restrictions Exclusion Criteria: * Clinical evidence or suspicion of active infection * Current or recent COVID-19 infection within 30 days * Serious infection within 6 months or more than 1 such episode within 18 months * Any history of a serious opportunistic infection within 18 months * Known history of immunodeficiency * History of gastrointestinal ulceration or perforation within 12 months * History of active diverticulitis, active inflammatory bowel disease, or GI abscess within 12 months * History of GI bleeding requiring hospitalization and/or transfusion within 6 months * New York Heart Association Class III or IV congestive heart failure and/or hospitalization for heart failure exacerbation within 6 months * Acute coronary syndrome, stroke, transient ischemic attack, or other thrombotic or thromboembolic event, or arterial revascularization procedure within 6 months

Locations (38)

Site - 0101

Birmingham, Alabama, United States

Site - 0135

Huntsville, Alabama, United States

Site - 0145

Huntsville, Alabama, United States

Site - 0104

Phoenix, Arizona, United States

Site - 0125

San Dimas, California, United States

Site - 0112

Outcomes

Primary Outcomes

Time-Averaged Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Through Day 90

Time-averaged percent change from baseline in high-sensitivity C-reactive protein (hs-CRP) through Day 90. The time-averaged percent change from baseline in hs-CRP is the area under the curve for percent change from baseline in hs-CRP divided by the number of days from the observed Day 30 to Day 90 visits (approximately 60 days if visits occur according to the protocol). The calculation uses the linear trapezoidal rule according to the observed visit days.

Time frame: Baseline through 90 days. Baseline is defined as the average of the last two available visits prior to study treatment administration.

Secondary Outcomes

Proportion of Participants With Time-averaged Hs-CRP < 2 mg/L (90 Days)

Proportion of participants with time-averaged hs-CRP \< 2 mg/L (90 Days)

Time frame: Baseline through 90 days. Baseline is defined as the average of the last two available visits prior to study treatment administration.

Time-Averaged Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Through Day 180

Time-averaged percent change from baseline in high-sensitivity C-reactive protein (hs-CRP) through Day 180. The time-averaged percent change from baseline in hs-CRP is the area under the curve for percent change from baseline in hs-CRP divided by the number of days from the observed Day 30 to Day 180 visits (approximately 150 days if visits occur according to the protocol). The calculation uses the linear trapezoidal rule according to the observed visit days.

Time frame: Baseline through 180 days. Baseline is defined as the average of the last two available visits prior to study treatment administration.

Evaluate the Pharmacokinetics by Measuring Serum Concentrations of TOUR006

Mean trough serum concentrations (ng/mL) of TOUR006 at Days 30, 60, 90,120, 150, 180, 240, 300, and 365. On dosing visits (BL and Day 30, 60, 90, 120, and 150 visits), PK samples were collected pre-dose. PK blood samples were collected on Study Days 180, 240, 300, and 365 at approximately the same time as the pre-dose samples were collected on previous dosing visits.

Time frame: Baseline through Day 365

Evaluate the Safety and Tolerability of TOUR006 in Participants With Elevated Cardiovascular Risk and CKD

Evaluates the percentage of participants with treatment emergent adverse events (AE), which includes serious and nonserious AEs. Treatment-emergent is defined as AEs that initiated or worsened after receiving at least 1 dose of study drug and includes a total of 141 participants.

Time frame: Baseline through Day 365.