rilematovir (JNJ-53718678) / J&J - LARVOL DELTA

Discovery of potential RSV fusion protein inhibitors from benzimidazole derivatives using QSAR, molecular docking, and ADMET evaluation methods. (PubMed, Mol Divers) - "Furthermore, we used the optimal toxicity model to assess their cytotoxicity, and identified 23 derivatives with predicted cytotoxicity lower than that of JNJ-53718678. Finally, through drug-likeness evaluation, ADMET analysis and molecular dynamics simulation, we obtained eight potential RSV inhibitors with higher inhibitory activity, lower cytotoxicity, and better pharmacokinetic properties compared to JNJ-53718678."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Two-Part Infant Study for Early Diagnosis of Respiratory Syncytial Virus (RSV) and Evaluation of JNJ-53718678 in RSV Acute Respiratory Tract Disease (clinicaltrials.gov) - P2 | N=22 | Completed | Sponsor: Janssen Research & Development, LLC | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

PRIMROSE: A Study of Rilematovir (JNJ-53718678) in Adult Outpatients With Respiratory Syncytial Virus (RSV) Infection (clinicaltrials.gov) - P2 | N=5 | Terminated | Sponsor: Janssen Research & Development, LLC | Phase classification: P2b ➔ P2

Phase classification • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development. (PubMed, Rev Med Virol) - "Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNA1

A Study to Explore the Antiviral Activity, Clinical Outcomes, Safety, Tolerability, and Pharmacokinetics of JNJ-53718678 at Two Dose Levels in Non-Hospitalized Adult Participants Infected With Respiratory Syncytial Virus (clinicaltrials.gov) - P2 | N=72 | Completed | Sponsor: Janssen Research & Development, LLC | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

CROCuS, a Phase II Study Evaluating the Antiviral Activity, Clinical Outcomes, and Safety of Rilematovir in Children Aged ≥ 28 Days and ≤ 3 Years with Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus. (PubMed, Paediatr Drugs) - P2 | "Data from the combined cohort suggest that rilematovir has a small but favorable antiviral effect of indeterminate clinical relevance compared with placebo, as well as a favorable safety profile. Safe and effective therapeutic options for RSV in infants and young children remain an unmet need."

Clinical data • Journal • P2 data • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A pilot phase 2a, randomised, double-blind, placebo-controlled study to explore the antiviral activity, clinical outcomes, safety, and tolerability of rilematovir at two dose levels in non-hospitalised adults with respiratory syncytial virus (RSV) infection. (PubMed, Clin Microbiol Infect) - P2a | "Rilematovir use, initiated early, suggests a potential clinical benefit in RSV-infected adults, with data supporting development of RSV therapeutic options."

Clinical data • Journal • P2a data • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Freesia Study Design: JNJ-53718678 in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Upper Respiratory Tract (ASH 2019) - "At some clinical centers oral or intravenous ribavirin, intravenous immunoglobulin or anti-RSV-enriched antibody preparations are used to treat RSV infection. This study will begin recruitment globally in the northern hemisphere in November 2019. This study will clarify the role JNJ-8678 may play in the treatment of RSV in a broader IC population, potentially addressing a substantial unmet medical need."

Clinical

Dose adjustment of rilematovir in combination with CYP3A4 inhibitors based on PBPK modeling and clinical data (ISIRV-RSV 2022) - No abstract available

Clinical data • Combination therapy

A Study of JNJ-53718678 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=25 | Terminated | Sponsor: Janssen Research & Development, LLC | N=52 ➔ 25 | Trial completion date: Dec 2022 ➔ Mar 2022 | Recruiting ➔ Terminated; A strategic decision was made to discontinue the study. The decision was not based on a safety concern.

Enrollment change • Trial completion date • Trial termination • Hepatology

Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection (clinicaltrials.gov) - P2 | N=246 | Terminated | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2024 ➔ Apr 2022 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2023 ➔ Apr 2022; Janssen made the strategic decision to discontinue the CROCuS study. This decision is not based on any safety concerns.

Clinical data • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study of JNJ-53718678 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1 | N=52 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Apr 2022 ➔ Dec 2022

Trial completion date • Hepatology

PRIMROSE: A Study of Rilematovir (JNJ-53718678) in Adult Outpatients With Respiratory Syncytial Virus (RSV) Infection (clinicaltrials.gov) - P2b | N=6 | Terminated | Sponsor: Janssen Research & Development, LLC | N=180 ➔ 6 | Trial completion date: Dec 2023 ➔ Mar 2022 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2023 ➔ Mar 2022; Janssen made the strategic decision to discontinue the PRIMROSE study. This decision is not based on any safety concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

DAISY: A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV) (clinicaltrials.gov) - P3 | N=28 | Terminated | Sponsor: Janssen Research & Development, LLC | N=737 ➔ 28 | Trial completion date: May 2025 ➔ Mar 2022 | Recruiting ➔ Terminated | Trial primary completion date: May 2025 ➔ Mar 2022; Janssen made the strategic decision to discontinue the DAISY study. This decision is not based on any safety concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection (clinicaltrials.gov) - P2 | N=294 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Mar 2023 ➔ Apr 2024

Clinical data • Trial completion date • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

FREESIA: Effects of JNJ-53718678 in Adult and Adolescent Participants Who Had a Hematopoietic Stem Cell Transplantation and Who Are Infected With Respiratory Syncytial Virus (RSV) (clinicaltrials.gov) - P2 | N=3 | Terminated | Sponsor: Janssen Sciences Ireland UC | Trial completion date: Aug 2025 ➔ Feb 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Aug 2022 ➔ Dec 2021; A strategic decision was made to discontinue the study. The decision was not based on a safety concern.

Clinical data • Trial completion date • Trial primary completion date • Trial termination • Bone Marrow Transplantation • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Transplantation

A Study in Healthy Adult Participants to Assess the Effects of Ciclosporin Administration on Rilematovir (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Completed

Trial completion

Probing In Silico the Benzimidazole Privileged Scaffold for the Development of Drug-like Anti-RSV Agents. (PubMed, Pharmaceuticals (Basel)) - "A deepen comparison of the related electrostatic features and H-bonding motifs allowed us to pave the way for the following molecular dynamic simulation of JNJ-53718678 and then to perform docking studies of the in-house library of potent benzimidazole-containing anti-RSV agents...Along with this, in silico prediction of absorption, distribution, metabolism, excretion (ADME) properties, and also of possible off-target events was performed. The results highlighted once more that the benzimidazole ring represents a privileged scaffold whose properties deserve to be further investigated for the rational design of novel and orally bioavailable anti-RSV agents."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study in Healthy Adult Participants to Assess the Effects of Ciclosporin Administration on Rilematovir (clinicaltrials.gov) - P1; N=18; Recruiting; Sponsor: Janssen Research & Development, LLC

Clinical • New P1 trial

FREESIA: Effects of JNJ-53718678 in Adult and Adolescent Participants Who Had a Hematopoietic Stem Cell Transplantation and Who Are Infected With Respiratory Syncytial Virus (RSV) (clinicaltrials.gov) - P2; N=3; Active, not recruiting; Sponsor: Janssen Sciences Ireland UC; Recruiting ➔ Active, not recruiting; N=375 ➔ 3

Clinical • Clinical data • Enrollment change • Enrollment closed • Bone Marrow Transplantation • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • Transplantation

PRIMROSE: A Study of Rilematovir (JNJ-53718678) in Adult Outpatients With Respiratory Syncytial Virus (RSV) Infection (clinicaltrials.gov) - P2b; N=180; Recruiting; Sponsor: Janssen Research & Development, LLC; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • PCR

A Study of JNJ-53718678 in Participants With Hepatic Impairment (clinicaltrials.gov) - P1; N=52; Recruiting; Sponsor: Janssen Research & Development, LLC; N=32 ➔ 52; Trial completion date: Nov 2021 ➔ Apr 2022; Trial primary completion date: Jun 2021 ➔ Apr 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Hepatology

Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection (clinicaltrials.gov) - P2; N=294; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial primary completion date: Dec 2022 ➔ Mar 2023

Clinical • Clinical data • Trial primary completion date • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • PCR

Study to Evaluate Safety and Antiviral Activity of Doses of JNJ-53718678 in Children (>=28 Days to <=3 Years) With Respiratory Syncytial Virus Infection (clinicaltrials.gov) - P2; N=294; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial completion date: Dec 2022 ➔ Mar 2023

Clinical • Clinical data • Trial completion date • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • PCR

DAISY: A Study of Rilematovir in Infants and Children and Subsequently in Neonates Hospitalized With Acute Respiratory Tract Infection Due to Respiratory Syncytial Virus (RSV) (clinicaltrials.gov) - P3; N=737; Recruiting; Sponsor: Janssen Research & Development, LLC; Initiation date: Jan 2021 ➔ Aug 2021

Clinical • Trial initiation date • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections