ruzotolimod (RG7854) / Roche - LARVOL DELTA

Piranga: A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=281 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | Trial completion date: Jul 2025 ➔ Jul 2024 | Trial primary completion date: Oct 2024 ➔ Jul 2024

Combination therapy • Trial completion • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Using exploratory pharmacokinetic and pharmacodynamic analyses to predict the probability of flu-like symptoms in healthy volunteers and patients with chronic hepatitis B treated with the toll-like receptor 7 agonist ruzotolimod. (PubMed, Clin Transl Sci) - "Ruzotolimod (Toll-like receptor 7 (TLR7) agonist, RG7854) is an oral, small molecule immuno-modulator activating the TLR 7 and is being evaluated in patients with CHB...The analysis also showed that the probability of flu-like symptoms occurrence increases with PD responses (IFN-α and IP-10). Dose reduction of ruzotolimod can be an effective way to reduce the magnitude of PD response, thus reducing the probability of study drug-related flu-like symptoms occurrence at all intensity in the participants who are highly sensitive to PD activation and intolerant to flu-like symptoms."

Clinical • IO biomarker • Journal • PK/PD data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1 • ISG15 • MX1

Piranga: A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Jan 2025 ➔ Jul 2025

Combination therapy • Trial completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Efficacy and safety of xalnesiran with and without an immunomodulator in virologically suppressed participants with chronic hepatitis B: end of study results from the phase 2, randomized, controlled, adaptive, open-label platform study (PIRANGA) (EASL-ILC 2024) - P2 | "Here, we report end of study results, including seroconversion and durability of HBsAg loss, of xalnesiran (RO7445482), an N-acetylgalactosamine (GalNAc)-conjugated small interfering ribonucleic acid (siRNA) targeting HBsAg transcripts with or without an immunomodulator: ruzotolimod (toll-like receptor 7 agonist, RO7020531) or pegylated interferon alfa-2a (Peg-IFN-α). The highest HBsAg loss and seroconversion rates were observed when xalnesiran was combined with an immunomodulator. The continued change in HBsAg loss rate between EOT and 48 wks post-EOT warrants adequate follow-up to confirm sustained functional cure. All treatments were generally safe and well tolerated."

Clinical • Immunomodulating • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531 (clinicaltrials.gov) - P1 | N=160 | Completed | Sponsor: Hoffmann-La Roche | N=46 ➔ 160

Enrollment change • Hepatitis B • Hepatology • Infectious Disease • Inflammation

EFFICACY AND SAFETY OF XALNESIRAN COMBINATION THERAPIES WITH AND WITHOUT AN IMMUNOMODULATOR IN VIROLOGICALLYSUPPRESSED PARTICIPANTS WITH CHRONIC HEPATITIS B: PRIMARY ENDPOINT RESULTS FROM THE PHASE 2, RANDOMIZED, CONTROLLED, ADAPTIVE, OPEN-LABEL PLATFORM STUDY (PIRANGA) (AASLD 2023) - P2 | "Here, we report the primary endpoint results of xalnesiran, a small interfering ribonucleic acid (siRNA) targeting the HBsAg coding region of the HBV genome (RO7445482, RG6346) in combination with nucleos(t)ide analogues (NUC), with or without an immunomodulator: pegylated interferon alfa-2a (Peg-IFN-α, Pegasys®), or ruzotolimod (toll-like receptor 7 agonist, RO7020531, RG7854). Xalnesiran combination therapies of 48 wks treatment duration were generally safe and well tolerated. Higher HBsAg loss rates were observed when xalnesiran was combined with an immunomodulator (PegIFN-α or ruzotolimod)."

Clinical • Combination therapy • Immunomodulating • Late-breaking abstract • P2 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IFNA1

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=280 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • Inflammation • PD-L1

TLR7 agonist RO7020531 versus placebo in healthy volunteers and patients with chronic hepatitis B virus infection: a randomised, observer-blind, placebo-controlled, phase 1 trial. (PubMed, Lancet Infect Dis) - P1 | "Due to acceptable safety and tolerability, RO7020531 should continue to be developed for the treatment of patients with chronic HBV infection."

Journal • P1 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Influenza • Pain • Respiratory Diseases

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=275 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: Aug 2023 ➔ Nov 2024 | Trial primary completion date: Mar 2023 ➔ May 2024

Combination therapy • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease • Inflammation • PD-L1

Toll-Like Receptor 7 Agonist RG7854 Mediates Therapeutic Efficacy and Seroconversion in Woodchucks With Chronic Hepatitis B. (PubMed, Front Immunol) - "Monotreatment with the two highest RG7854 doses and combination treatment with the highest RG7854 dose and entecavir (ETV) suppressed viral replication, led to loss of viral antigens, and induced seroconversion in responder woodchucks. The study concluded that finite, oral RG7854 treatment can induce a SVR in woodchucks that is based on the retrieval of antiviral innate and adaptive immune responses. This supports future investigation of the TLR7 agonist as an immunotherapeutic approach for achieving functional cure in patients with CHB."

Journal • Hematological Disorders • Hepatitis B • Hepatology • Immunology • Infectious Disease • Inflammation • Neutropenia • Thrombocytopenia

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2 | N=275 | Recruiting | Sponsor: Hoffmann-La Roche | N=210 ➔ 275

Combination therapy • Enrollment change • Hepatitis B • Hepatology • Infectious Disease • Inflammation • PD-L1

[VIRTUAL] TARGETING TLR7 WITH RO7020531: PHASE 1 STUDY OF THE SAFETY, PK, PD AND ANTIVIRAL ACTIVITY IN PATIENTS WITH CHRONIC HEPATITIS B NOT RECEIVING ANTIVIRAL THERAPY (AASLD 2021) - "RO7020531 was safe and acceptably tolerated in naïve CHB patients and stimulated TLR7 activation, resulting in robust antiviral responses. It is currently under further investigation in the phase 2 PIRANGA platform trial of combination therapy to achieve functional cure in HBV."

Clinical • IO biomarker • Late-breaking abstract • P1 data • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease • IFNA1 • TLR7

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531 (clinicaltrials.gov) - P1; N=46; Completed; Sponsor: Hoffmann-La Roche; Active, not recruiting ➔ Completed

Clinical • Trial completion • Hepatitis B • Hepatology • Infectious Disease • Inflammation • IL10 • IL6 • TNFA

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531 (clinicaltrials.gov) - P1; N=46; Active, not recruiting; Sponsor: Hoffmann-La Roche; Recruiting ➔ Active, not recruiting; N=157 ➔ 46

Enrollment change • Enrollment closed • Hepatitis B • Hepatology • Infectious Disease • IL10 • IL6 • TNFA

[VIRTUAL] Influence of TLR7 polymorphism and sex on pharmacodynamic response to TLR7 agonist (RO7020531) (APASL 2021) - No abstract available

PK/PD data

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2; N=210; Recruiting; Sponsor: Hoffmann-La Roche; N=60 ➔ 210; Trial completion date: Mar 2023 ➔ Aug 2023; Trial primary completion date: Dec 2021 ➔ Mar 2023

Clinical • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Hepatitis B • Hepatology • Infectious Disease

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Jul 2022 ➔ Mar 2023

Clinical • Combination therapy • Trial completion date • Hepatitis B • Hepatology • Infectious Disease

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: Apr 2022 ➔ Jul 2022

Clinical • Combination therapy • Trial completion date • Hepatitis B • Hepatology • Infectious Disease

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531 (clinicaltrials.gov) - P1; N=150; Recruiting; Sponsor: Hoffmann-La Roche; Trial completion date: May 2020 ➔ Feb 2021; Trial primary completion date: May 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • Hepatitis B • Infectious Disease • IL10 • IL6 • TNFA

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Hoffmann-La Roche; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Hepatitis B • Infectious Disease

A Single and Multiple Ascending Dose Study of Toll-Like Receptor 7 (TLR 7) Agonist (RO7020531) in Chinese Healthy Volunteers. (PubMed, Clin Transl Sci) - "Flu-like symptoms were associated with higher interferon-α levels. RO7020531 was safe and acceptably tolerated in Chinese healthy volunteers with a multiple 150 mg QOD dose regimen."

Clinical • IO Biomarker • Journal • Hepatitis B • Immunology • Infectious Disease • Oncology

Transcriptional response to RO7020531, a novel double prodrug of a toll-like receptor 7 agonist, in whole blood of healthy subjects and chronic hepatitis B patients (APASL 2020) - No abstract available

Clinical

A Trial To Evaluate The Efficacy And Safety Of Multiple Combination Therapies In Participants With Chronic Hepatitis B (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: Hoffmann-La Roche

Clinical • Combination therapy • New P2 trial

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531 (clinicaltrials.gov) - P1; N=150; Recruiting; Sponsor: Hoffmann-La Roche; Trial primary completion date: Nov 2019 ➔ May 2020

Clinical • Trial primary completion date • IL10 • IL6

SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND VIRAL DATA AFTER 6-WEEKS OF DOSING WITH TLR7 AGONIST RO7020531 IN CHRONIC HEPATITIS B PATIENTS (AASLD 2019) - "RO7020531 was safe and acceptably tolerated in 6-week QOD dosing in CHB patients, with predictable PK and solid evidence of immune activation across all patients. Conclusions on HBsAg dynamics could not be made due to the short treatment duration. RO7020531 is currently being tested in not-treated CHB patients."

Clinical • IO Biomarker • PK/PD data