mosnodenvir (JNJ-1802) / J&J - LARVOL DELTA

An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge (clinicaltrials.gov) - P2 | N=56 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Recruiting ➔ Completed

Trial completion • Dengue Fever • Infectious Disease

Recent advances in the control of dengue fever using herbal and synthetic drugs. (PubMed, Heliyon) - "Extensive investigations have been conducted on various synthetic compounds, including JNJ-1802, 1,4-pyran naphthoquinones, and arylnaphthalene lignan derivatives...This aspect underscores the need for both highly effective immunization strategies and therapeutic interventions, whether derived from botanical sources or through synthetic manufacturing, that exhibit low adverse effects. This review examines innovative approaches to DENV prevention and treatment, encompassing both phytochemical and synthetic therapeutic strategies."

Journal • Review • Dengue Fever • Hematological Disorders • Infectious Disease

Mechanistic insights into dengue virus inhibition by a clinical trial compound NITD-688. (PubMed, Proc Natl Acad Sci U S A) - "Consistent with this mechanism, NITD-688 retains greater potency in cellular assays with delayed treatment compared to JNJ-1802, another NS4B inhibitor that has been studied in Phase II clinical trials. Together, these findings provide critical insights into the mechanism of action of NITD-688, facilitating the development of novel flavivirus NS4B inhibitors and informing future clinical interventions against DENV."

Journal • Dengue Fever

A Study of JNJ-64281802 for the Prevention of Dengue Infection (clinicaltrials.gov) - P2 | N=1256 | Terminated | Sponsor: Janssen Research & Development, LLC | N=1850 ➔ 1256 | Trial completion date: May 2025 ➔ Jun 2024 | Recruiting ➔ Terminated | Trial primary completion date: May 2025 ➔ Jun 2024; The study was stopped due to portfolio reprioritization. This decision is not based on any safety concerns.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Dengue Fever • Infectious Disease

A Study of JNJ-64281802 Against Dengue Serotype 1 Infection in a Dengue Human Challenge Model in Healthy Adult Participants (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Janssen Research & Development, LLC | N=54 ➔ 0 | Suspended ➔ Withdrawn

Enrollment change • Trial withdrawal • Dengue Fever • Infectious Disease

Genomic surveillance reveals a dengue 2 virus epidemic lineage with a marked decrease in sensitivity to Mosnodenvir. (PubMed, Nat Commun) - "These results call for increased genomic surveillance, in particular to track lineages with resistance mutations. These efforts should allow to better assess the activity profile of DENV treatments in development against circulating strains."

Journal • Dengue Fever

Orthoflaviviral Inhibitors in Clinical Trials, Preclinical In Vivo Efficacy Targeting NS2B-NS3 and Cellular Antiviral Activity via Competitive Protease Inhibition. (PubMed, Molecules) - "NS3-NS4B inhibitors, such as JNJ-64281802 and EYU688, show promise, recently entering clinical trials, underscoring the importance of developing novel viral replication inhibitors targeting viral machinery. To date, the only NS2B-NS3 inhibitor that has undergone clinical trials is doxycycline, however, its mechanism of action and clinical efficacy as viral growth inhibitor require additional investigation. SYC-1307, an allosteric inhibitor, exhibits high in vivo efficacy, while temoporfin and methylene blue represent promising orthosteric non-competitive inhibitors. Compound 71, a competitive NS2B-NS3 inhibitor, emerges as a leading preclinical candidate due to its high cellular antiviral efficacy, minimal cytotoxicity, and favorable in vitro pharmacokinetic parameters. Challenges remain in developing competitive NS2B-NS3 inhibitors, including appropriate biochemical inhibition assays as well as the selectivity and conformational flexibility of the protease, complicating..."

Journal • Preclinical • Review • Dengue Fever • Infectious Disease

Trends and insights in dengue virus research globally: a bibliometric analysis (1995-2023). (PubMed, J Transl Med) - "This bibliometric study underscores the critical role of interdisciplinary collaboration in advancing DENV research, identifying key trends and areas needing further exploration, including host-virus dynamics, the development and application of antiviral drugs and vaccines, and the use of artificial intelligence. It advocates for strengthened partnerships across various disciplines to effectively tackle the challenges posed by DENV."

Journal • Dengue Fever • DDX58 • IFNA1 • NFKB1 • STAT1

Discovery of JNJ-1802 as clinical candidate for the prevention and treatment of dengue (ACS-Fall 2024) - "We will also report on its potent and pan-serotype in vivo efficacy in mice and non-human primates. JNJ-1802 has successfully completed a phase 1 first-in-human clinical study in healthy volunteers which supports progressing the development of the compound into phase 2 clinical studies."

Clinical • Dengue Fever • Infectious Disease

A Study of JNJ-64281802 Against Dengue Serotype 1 Infection in a Dengue Human Challenge Model in Healthy Adult Participants (clinicaltrials.gov) - P2 | N=54 | Suspended | Sponsor: Janssen Research & Development, LLC | Trial primary completion date: Jan 2024 ➔ Sep 2027

Trial primary completion date • Dengue Fever • Infectious Disease

Discovery of JNJ-1802, a First-in-Class Pan-Serotype Dengue Virus NS4B Inhibitor. (PubMed, J Med Chem) - "The observed oral bioavailability of JNJ-1802 across preclinical species, its low clearance in human hepatocytes, the absence of major in vitro pharmacology safety alerts, and a dose-proportional increase in efficacy against DENV-2 infection in mice were all supportive of its selection as a development candidate against dengue. JNJ-1802 is being progressed in clinical studies for the prevention or treatment of dengue."

Journal • Dengue Fever • Infectious Disease

A Study of JNJ-64281802 in Participants With Confirmed Dengue Fever (clinicaltrials.gov) - P2 | N=5 | Terminated | Sponsor: Janssen Research & Development, LLC | Phase classification: P2a ➔ P2

Phase classification • Dengue Fever

A Study of JNJ-64281802 Against Dengue Serotype 1 Infection in a Dengue Human Challenge Model in Healthy Adult Participants (clinicaltrials.gov) - P2 | N=54 | Suspended | Sponsor: Janssen Research & Development, LLC | Phase classification: P2a ➔ P2 | Trial completion date: Apr 2024 ➔ Dec 2027

Phase classification • Trial completion date • Dengue Fever • Infectious Disease

An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Trial completion date • Dengue Fever • Infectious Disease

Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics. (PubMed, PLoS Comput Biol) - "Viral RNA suppression to below the limit of detection was achieved at concentrations of >1.6 nM, with a median concentration exhibiting 50% of maximal inhibitory effect (IC50) of 1.23x10-02 nM and 1.28x10-02 nM for the DENV-2/RL and DENV-2/16681 strains, respectively. This work provides important insight into the in-vitro inhibitory effect of JNJ-1802 and presents a first step towards a modelling framework to support characterization of viral kinetics and drug effect across different host systems."

Journal • Preclinical • Dengue Fever • Infectious Disease

An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Phase classification: P2a ➔ P2

Phase classification • Dengue Fever • Infectious Disease

JNJ-1802 for Pre-exposure Prophylaxis of Dengue (ASTMH 2023) - "Sponsored by Johnson & Johnson"

Dengue Fever

Antiviral activity, safety, and pharmacokinetics of JNJ-1802 as pre-exposure prophylaxis against DENV-3 in a human challenge model (ASTMH 2023) - P2a | "In this prophylaxis human challenge model, the high dose of JNJ-1802 significantly reduced DENV-3 viral load versus placebo with no relevant clinical safety findings. JNJ-1802 is currently being evaluated in a prophylaxis phase 2 clinical field trial."

Clinical • Late-breaking abstract • PK/PD data • Dengue Fever • Infectious Disease

A Study of JNJ-64281802 in Participants With Confirmed Dengue Fever (clinicaltrials.gov) - P2a | N=5 | Terminated | Sponsor: Janssen Research & Development, LLC | N=150 ➔ 5 | Trial completion date: Nov 2024 ➔ Mar 2023 | Suspended ➔ Terminated; Feasibility of enrollment impacted by COVID

Enrollment change • Trial completion date • Trial termination • Dengue Fever

An Evaluation of Repeated Oral Doses of JNJ-64281802 Against DENV-3 Challenge (clinicaltrials.gov) - P2a | N=54 | Recruiting | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Trial completion date: Jun 2023 ➔ Aug 2024

Trial completion date • Dengue Fever • Infectious Disease

A Study of JNJ-64281802 in Participants With Confirmed Dengue Fever (clinicaltrials.gov) - P2a | N=150 | Suspended | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Suspended

Trial suspension • Dengue Fever

Safety, tolerability and pharmacokinetics of JNJ-1802, a pan-serotype dengue direct antiviral small molecule, in a Phase 1, double-blind, randomized, dose-escalation study in healthy volunteers. (PubMed, Clin Infect Dis) - "Pharmacokinetics and safety results of JNJ-1802 support further clinical development for the treatment and prevention of dengue infection."

Journal • P1 data • PK/PD data • CNS Disorders • Dengue Fever • Depression • Infectious Disease • Psychiatry

A Study of JNJ-64281802 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=33 | Completed | Sponsor: Janssen Research & Development, LLC | Recruiting ➔ Completed | N=48 ➔ 33 | Trial completion date: Aug 2023 ➔ Dec 2022 | Trial primary completion date: Aug 2023 ➔ Dec 2022

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Blocking NS3-NS4B interaction inhibits dengue virus in non-human primates. (PubMed, Nature) - "JNJ-1802 has successfully completed a phase I first-in-human clinical study in healthy volunteers and was found to be safe and well tolerated. These findings support the further clinical development of JNJ-1802, a first-in-class antiviral agent against dengue, which is now progressing in clinical studies for the prevention and treatment of dengue."

Journal • Dengue Fever • Infectious Disease

The pipeline for drugs for control and elimination of neglected tropical diseases: 1. Anti-infective drugs for regulatory registration. (PubMed, Parasit Vectors) - "Considering drugs approved for an NTD by at least one stringent regulatory authority: fexinidazole, included in WHO guidelines for Trypanosoma brucei gambiense African trypanosomiasis, is in development for Chagas disease. Moxidectin, registered in 2018 for treatment of individuals ≥ 12 years old with onchocerciasis, is undergoing studies to extend the indication to 4-11-year-old children and obtain additional data to inform WHO and endemic countries' decisions on moxidectin inclusion in guidelines and policies...Considering drugs in at least Phase 2 clinical development, a submission is being prepared for registration of acoziborole as an oral treatment for first and second stage T.b. gambiense African trypanosomiasis. Bedaquiline, registered for tuberculosis, is being evaluated for multibacillary leprosy. Phase 2 studies of emodepside and flubentylosin in O. volvulus-infected individuals are ongoing; studies for Trichuris trichuria and hookworm are planned. A..."

Journal • Review • Dengue Fever • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis