A Study to Evaluate the Efficacy, Safety, Pharmacodynamics (PD), and Pharmacokinetics (PK) of Selnoflast in Reducing Vascular Inflammation in Participants With Atherosclerosis at Risk for Major Adverse Cardiac Events (RIVULET)

A Phase IIa, Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Selnoflast in Reducing Vascular Inflammation in Patients With Atherosclerosis at Risk for Major Adverse Cardiac Events

The main purpose of the study is to evaluate the efficacy of selnoflast compared with placebo in participants with atherosclerosis, at high-risk for major adverse cardiovascular event (MACE), who are currently on standard-of-care (SOC) therapy.

Study Overview

• Status: Recruiting
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Selnoflast

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GC46102 https://forpatients.roche.com/; Phone Number: 888-662-6728; Email: global-roche-genentech-trials@gene.com

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90210
      • Recruiting
      • Cardiovascular Research Foundation of Southern California
    • Irvine, California, United States, 92604
      • Recruiting
      • Amnova Clinical Research
    • West Hills, California, United States, 91307
      • Recruiting
      • Alliance Clinical West Hills (Focus Clinical Research)
  • Indiana
    • Hammond, Indiana, United States, 46324
      • Recruiting
      • Asha Clinical Research-Munster,Llc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • Recruiting
      • Preferred Primary Care Physicians, Inc
  • Washington
    • Redmond, Washington, United States, 98036
      • Recruiting
      • Eastside Research Associates, LLC dba Era Health Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed evidence of atherosclerosis
• Left or right carotid TBR ≥ 1.8 or aorta TBR ≥ 2.0 on centrally-assessed 18F-fluorodeoxyglucose-Positron Emission Tomography (18F-FDG-PET) scan
• Stable treatment of atherosclerosis through the use of SOC medications or revascularization
• QT interval corrected through use of Fridericia's formula (QTcF) of ≤ 450 milliseconds (ms) in men and ≤ 470 ms in women by a single 12-lead electrocardiogram (ECG) recording

Exclusion Criteria:

• Individuals with Class III and IV heart failure
• Uncontrolled cardiac arrhythmia
• Uncontrolled hypertension
• Suspected or known immunocompromised state
• Planned procedure or surgery during the study and any major surgery within 90 days prior to screening Visit 1
• History of malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
• Positive test results for hepatitis B (HBV) infection at screening
• Positive hepatitis C virus (HCV) antibody test at screening
• Positive human immunodeficiency virus (HIV) test at screening
• Treatment with any live vaccine within 28 days prior to the first dose of study drug until the end of the study
• Treatment with other non-live vaccines within 14 days prior to the first dose of study drug until the end of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Selnoflast; Participants will receive selnoflast, orally (PO), twice a day (BID) for 12 weeks.	Drug: Selnoflast; Selnoflast will be administered as per the schedule specified in the respective arm.; Other Names: RO7486967
Placebo Comparator: Placebo; Participants will receive placebo, PO, BID for 12 weeks.	Drug: Placebo; Placebo will be administered as per the schedule specified in the respective arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mdsTBR (Most-diseased Segment TBR [Target-to-background Ratio]) of Index Vessel From Baseline to Week 12 in Participants With Baseline Elevated hsCRP (≥ 2 milligrams per liter [mg/L])	hsCRP=high-sensitivity C-reactive protein.	Baseline up to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in mdsTBR of Index Vessel at Week 12 in all Participants (hsCRP < 2 mg/L and ≥ 2mg/L)		Baseline and Week 12
Change From Baseline in mdsTBR of Carotids at Week 12 in all Participants (hsCRP < 2 mg/L and ≥ 2 mg/L)		Baseline and Week 12
Change From Baseline in mdsTBR of Carotids at Week 12 in Participants With Baseline Elevated hsCRP (≥ 2 mg/L)		Baseline and Week 12
Change From Baseline in Active Segments TBR and the Whole Vessel TBR of the Index Vessel at Week 12 in all Participants (hsCRP < 2 mg/L and ≥ 2 mg/L)		Baseline and Week 12
Change From Baseline in Active Segments TBR and the Whole Vessel TBR of the Index Vessel at Week 12 in Participants With Baseline Elevated hsCRP (≥ 2 mg/L)		Baseline and Week 12
Number of Participants With Adverse Events (AEs) and Severity of AEs Determined According to the NCI CTCAE v5.0 Grading Scale	NCI CTCAE v5.0 = National Cancer Institute's Common Terminology Criteria for Adverse Events, Version 5.0.	Up to approximately 20 weeks
Plasma Concentration of Selnoflast at Specified Timepoints		Up to 12 weeks

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): February 28, 2028

Study Registration Dates

• First Submitted: February 25, 2026
• First Submitted That Met QC Criteria: February 25, 2026
• First Posted (Actual): March 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: GC46102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No