Treatment of chronic hepatitis D with peginterferon lambda-the phase 2 LIMT-1 clinical trial

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc..

BACKGROUND AND AIMS: HDV infection leads to the most aggressive form of human viral hepatitis for which there is no FDA-approved therapy. PEG IFN-lambda-1a (Lambda) has previously demonstrated a good tolerability profile in HBV and HCV patients compared to PEG IFN-alfa. The goal of Phase 2 LIMT-1 trial was to evaluate the safety and efficacy of Lambda monotherapy in patients with HDV.

APPROACH AND RESULTS: An open-label study of Lambda 120 or 180 mcg, administered once weekly by subcutaneous injections for 48 weeks, followed by 24 weeks of posttreatment follow-up. Thirty-three patients were allocated to Lambda 180 mcg (n=14) or 120 mcg (n=19). Baseline mean values: HDV RNA 4.1 log10 IU/mL (SD±1.4); ALT 106 IU/L (35-364); and bilirubin 0.5 mg/dL (0.2-1.2). Intention-to-treat rates of virologic response to Lambda 180 mcg and 120 mcg, 24 weeks following treatment cessation were 5 of 14(36%) and 3 of 19 (16%), respectively. The posttreatment response rate of 50% was seen in low BL viral load (≤4 log10) on 180 mcg. Common on-treatment adverse events included flu-like symptoms and elevated transaminase levels. Eight (24%) cases of hyperbilirubinemia with or without liver enzyme elevation, leading to drug discontinuation, were mainly observed in the Pakistani cohort. The clinical course was uneventful, and all responded favorably to dose reduction or discontinuation.

CONCLUSIONS: Treatment with Lambda in patients with chronic HDV may result in virologic response during and following treatment cessation. Clinical phase 3 development of Lambda for this rare and serious disease is ongoing.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:77

Enthalten in:

Hepatology (Baltimore, Md.) - 77(2023), 6 vom: 01. Juni, Seite 2093-2103

Sprache:

Englisch

Beteiligte Personen:

Etzion, Ohad [VerfasserIn]
Hamid, Saeed [VerfasserIn]
Lurie, Yoav [VerfasserIn]
Gane, Edward J [VerfasserIn]
Yardeni, David [VerfasserIn]
Duehren, Sarah [VerfasserIn]
Bader, Nimrah [VerfasserIn]
Nevo-Shor, Anat [VerfasserIn]
Channa, Saleh Muhammad [VerfasserIn]
Cotler, Scott J [VerfasserIn]
Mawani, Minaz [VerfasserIn]
Parkash, Om [VerfasserIn]
Dahari, Harel [VerfasserIn]
Choong, Ingrid [VerfasserIn]
Glenn, Jeffrey S [VerfasserIn]

Links:

Volltext

Themen:

3WJQ0SDW1A
Antiviral Agents
Clinical Trial, Phase II
Interferon-alpha
Interleukins
Journal Article
Polyethylene Glycols
Recombinant Proteins

Anmerkungen:

Date Completed 18.05.2023

Date Revised 14.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1097/HEP.0000000000000309

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM353073105