Delving into the Latest Updates on JNJ-440 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

ALS-003440, JNJ 440, JNJ-0440

+ [2]

Target

HBV capsid

Action

inhibitors

Mechanism

HBV capsid inhibitors(HBV capsid inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Hepatitis B, Chronic

Originator Organization

Alios BioPharma, Inc.

Active Organization-

Inactive Organization

Alios BioPharma, Inc.

Janssen Research & Development LLC

Janssen Pharmaceuticals, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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A Multipart Phase 1, Double-Blind, Randomized, Placebo-Controlled, First-in-Human, Study of Orally Administered JNJ-440 to Evaluate the Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses Including Food Effect Evaluation (Part 1); After Multi-Day Dosing (Part 2) in Healthy Subjects; and After Multiple (Ascending) Doses in Subjects With Chronic Hepatitis B (Part 3)

The purpose of this study is to evaluate the safety and tolerability of JNJ-440 in healthy and Chronic Hepatitis B (CHB) participants after single and multiple doses; and to evaluate the pharmacokinetic (PK) of JNJ-440 in healthy participants and in CHB participants following single and multiple dose regimens, administered alone (healthy participants and CHB participants).

Start Date26 Mar 2018

Sponsor / Collaborator

Alios BioPharma, Inc.

100 Clinical Results associated with JNJ-440

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100 Translational Medicine associated with JNJ-440

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100 Patents (Medical) associated with JNJ-440

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2

Literatures (Medical) associated with JNJ-440

31 Mar 2022·The Journal of antimicrobial chemotherapyQ2 · MEDICINE

Safety, antiviral activity and pharmacokinetics of JNJ-64530440, a novel capsid assembly modulator, as 4 week monotherapy in treatment-naive patients with chronic hepatitis B virus infection

Q2 · MEDICINE

Article

Author: Dragone, Leonard ; Yogaratnam, Jeysen Z. ; Lenz, Oliver ; Kakuda, Thomas N. ; Patel, Megha ; Schwabe, Christian ; Berliba, Elina ; Gane, Ed J. ; Westland, Chris ; Ghicavii, Nelea ; Verbinnen, Thierry ; Jucov, Alina ; Van Remoortere, Pieter ; Talloen, Willem ; Tangkijvanich, Pisit

Abstract:

Objectives:

We investigated JNJ-64530440 (a hepatitis B virus capsid assembly modulator) safety, antiviral activity and pharmacokinetics in patients with chronic hepatitis B (CHB) (Phase 1b, NCT03439488).

Methods:

Twenty treatment-naive, HBeAg-positive or -negative CHB patients were randomized 4‍:‍1 to JNJ-64530440 750 mg once or twice daily, or placebo for 28 days.

Results:

All patients (mean age 43.8 years; 85% male; 70% White; 20% HBeAg positive) completed dosing/28 day follow-up. Mild-to-moderate treatment-emergent adverse events occurred in 3/4 (placebo), 6/8 (once-daily) and 4/8 (twice-daily) patients; mostly fatigue, increased alanine aminotransferase, decreased neutrophil count, and headache. Hepatitis B virus (HBV) DNA was substantially reduced; mean (range) changes from baseline at day 29 were: −3.2 (−2.4 to −3.9) (once-daily) and −3.3 (−2.6 to −4.1) (twice-daily) log10 IU/mL; placebo 0.1 (0.7 to −0.6) log10 IU/mL. HBV DNA levels were below the lower limit of quantification (LLOQ) in 5/8 (once-daily) and 3/8 (twice-daily) patients. For patients with detectable baseline HBV RNA, mean (SE) changes versus baseline in HBV RNA at day 29 were: −2.65 (0.81) (once-daily) and −2.94 (0.33) (twice-daily) log10 copies/mL. HBV RNA levels were ‘target not detected’ in 4/6 (once-daily) and 3/7 (twice-daily) patients. JNJ-64530440 pharmacokinetics in CHB patients were comparable with those in healthy volunteers.

Conclusions:

JNJ-64530440 750 mg once-daily or twice-daily for 28 days was well tolerated and achieved potent antiviral activity in CHB patients.

01 Jan 2021·Antiviral therapyQ4 · MEDICINE

Pharmacokinetics, safety and tolerability of single- and multiple-ascending doses of JNJ-64530440, a novel hepatitis B virus capsid assembly modulator, in healthy volunteers

Q4 · MEDICINE

Article

Author: Gane, Edward J ; Westland, Christopher ; Chanda, Sushmita ; Yogaratnam, Jeysen Z ; Fry, John ; van Remoortere, Pieter ; Kakuda, Thomas N ; Snoeys, Jan ; Schwabe, Christian ; Lenz, Oliver ; Patel, Megha ; Vuong, Jennifer ; Talloen, Willem

Background:

Pharmacokinetics and safety of JNJ-64530440, a hepatitis B virus capsid assembly modulator producing normal empty capsids (CAM-N), in healthy volunteers were evaluated.

Methods:

This Phase I study (NCT03439488) was a double-blind, randomised, placebo-controlled study. Adults ( n = 10/cohort, five Asian/five non-Asian), randomised 4:1, received single-ascending doses of oral JNJ-64530440 (first- and second-generation formulations) or placebo under fasted (50, 150, 300 and 900 mg) or fed (300, 750, 1,000, 2000 and 4000 mg) conditions. Multiple-ascending doses of 750 or 2000 mg once daily and 750 mg twice daily JNJ-64530440 (second-generation formulation) for 7 days were evaluated. Pharmacokinetic parameters were estimated from plasma concentrations. Safety was assessed throughout.

Results:

Less than dose-proportional increases in maximum plasma concentrations (Cmax) and area under the plasma concentration–time curves (AUCs) were observed across the doses. Mean plasma half-lives ranged from 9.3 to 14.5 h. Cmax and AUC were ∼two fold higher under fed versus fasting conditions and slightly higher in Asians versus Caucasians. JNJ-64530440 doses ≥750 mg achieved plasma levels higher than protein-binding adjusted concentrations demonstrating in vitro antiviral activity. No serious adverse events (AEs), treatment discontinuations or dose-limiting toxicities were seen. AE frequency/severity did not increase with dose.

Conclusions:

Single (up to 4000 mg) and multiple doses (up to 2000 mg for 7 days) of JNJ-64530440 were well tolerated in healthy volunteers. Multiple doses ≥750 mg/day achieved plasma concentrations expected to have antiviral activity that may lower hepatitis B surface antigen. No clinically relevant differences in tolerability or pharmacokinetic parameters were seen between Asians versus Caucasians.

100 Deals associated with JNJ-440

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis B, Chronic	Phase 1	United States	Alios BioPharma, Inc.	26 Mar 2018
Hepatitis B, Chronic	Phase 1	New Zealand	Alios BioPharma, Inc.	26 Mar 2018
Hepatitis B, Chronic	Phase 1	Thailand	Alios BioPharma, Inc.	26 Mar 2018
Hepatitis B, Chronic	Phase 1	Ukraine	Alios BioPharma, Inc.	26 Mar 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03439488 (Pubmed) Manual	Phase 1	Hepatitis B	-	JNJ-64530440	zetjdwgoew(menlcaoyhl) = ∼two fold higher under fed versus fasting conditions and slightly higher in Asians versus Caucasians wwaadqestn (ihbxwawifc ) View more	Positive	01 Jan 2021
NCT03439488 (EASL2019)	Phase 1	-	100	JNJ-0440	sczutvzlya(vjlnuyqjyk) = There were no withdrawals due to adverse events (AEs), serious AEs, or dose limiting toxicities. AEs and lab abnormalities were mostly Grade 1 or 2. Related AEs (n â‰¥ 2) included headache (n = 8), fatigue (n = 2) and contusion (n = 2). No clinically relevant changes in electrocardiograms were observed. gtkwhttxpn (oahdxgstji )	Positive	12 Apr 2019