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

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

Monitoring Severity of Respiratory Syncytial Virus (RSV) in Infants and Young Children Using the Pediatric RSV Electronic Severity and Outcome Rating System (PRESORS): Results of Initial Quantitative Validation. (PubMed, Patient Relat Outcome Meas) - "PRESORS ClinRO and ObsRO data were collected in a 28-day randomized, double-blind, Phase 1b trial of JNJ-53718678 or placebo in infants and children ≤24 months of age treated for RSV infection in hospitals...PRESORS ClinRO and ObsRO can inform endpoints and enable monitoring the clinical course of RSV in pediatric trials. Improved alignment between ClinRO and ObsRO and revisions ensuring caregivers can assess all signs will be addressed in revised PRESORS."

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