Chronic Kidney Diseases, Chronic Kidney Insufficiency, Chronic Renal Diseases, Chronic Renal Insufficiency, C-Reactive Protein, High Sensitivity C-Reactive Protein, hsCRP, Hs-CRP, Kidney Insufficiency, Chronic
Conditions
Keywords
Interleukin-6, IL-6, IL6, Interleukin-6 Inhibitors, Anti-interleukin-6 Agents, Anti-inflammatory Agents, Antiinflammatory Agent, Antiinflammatory Agents, Agents, Antiinflammatory, Anti-inflammatory Agent
Brief summary
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.
Detailed description
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.
Interventions
DRUGTOUR006 - 50 MG
TOUR006 50 MG
DRUGTOUR006 - 25 MG
TOUR006 25 MG
DRUGTOUR006 - 15 MG
TOUR006 15 MG
OTHERPlacebo
Placebo
Sponsors
Tourmaline Bio, Inc., a Novartis Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-Averaged Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Through Day 90 | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants With Time-averaged Hs-CRP < 2 mg/L (90 Days) | Baseline through 90 days. Baseline is defined as the average of the last two available visits prior to study treatment administration. | Proportion of participants with time-averaged hs-CRP \< 2 mg/L (90 Days) |
| Time-Averaged Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Through Day 180 | Baseline through 180 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. 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. |
| Evaluate the Pharmacokinetics by Measuring Serum Concentrations of TOUR006 | Baseline through Day 365 | 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. |
| Evaluate the Safety and Tolerability of TOUR006 in Participants With Elevated Cardiovascular Risk and CKD | Baseline through Day 365. | 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. |
Countries
United States
Contacts
STUDY_DIRECTORClinical Trials
Tourmaline Bio
Participant flow
Recruitment details
Participants were recruited from 49 study centers in the United States between May 2024 and December 2024. Of 49 sites, 38 sites enrolled participants. The first participant was enrolled on May 15, 2024 and the last participant was enrolled on December 3, 2024.
Pre-assignment details
Of the 454 initial and re-screenings (where applicable), 143 were randomized to receive treatment or placebo.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71 years |
| CKD Stage (IWRS) CKD Stage 3 or UPCR ≥ 200 mg/g and eGFR ≥ 60 mL/min/1.73m2 | 27 Participants |
| CKD Stage (IWRS) CKD Stage 4 | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| hs-CRP, mg/L | 4.73 mg/L |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Region of Enrollment United States | 31 participants |
| Sex/Gender, Customized Female | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 1 / 35 | 1 / 35 | 0 / 35 |
| other Total, other adverse events | 22 / 36 | 21 / 35 | 21 / 35 | 21 / 35 |
| serious Total, serious adverse events | 6 / 36 | 7 / 35 | 6 / 35 | 3 / 35 |
Outcome results
None listed