Clinical trial NCT05683548: Replicor Compassionate Access Program
Official title: Compassionate Use Access to REP 2139-Mg for the Treatment of Chronic HBV Infection or Chronic HBV / HDV Co-infection
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Viral Hepatitis B
Viral Hepatitis D
Cirrhosis, Liver
Decompensated Cirrhosis
Ascites Hepatic
Varices, Esophageal
Hepatocellular Carcinoma
Keywords: nucleic acid polymer
REP 2139-Mg
HBV
HDV
cirrhosis
functional cure
Lead sponsor: Replicor Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT

Brief summary: The goal of this compassionate access program is to provide early access to REP 2139-Mg for patients with HBV mono-infection or HBV / HDV co-infection who either have advanced (decompensated) cirrhosis or who have failed to response to other other antiviral agents either approved or under development and who are in danger of progressing to decompensated cirrhosis.

This compassionate access program will provide access to a once weekly regimen of subcutaneously (SC) administered REP 2139-Mg for a period of 48 weeks with the goal of achieving functional cure of HDV and or HBV, with the reversal of liver disease in the absence of antiviral therapy. The safety, tolerability and efficacy of SC REP 2139-Mg will be monitored during and after therapy

Detailed description: Nucleic acid polymers (NAPs) block the assembly of hepatitis B virus (HBV) subviral particles and bind to the small and large hepatitis delta virus (HDV) antigen. In chronic HBV mono-infection, this leads to rapid HBsAg loss and in chronic HBV / HDV co-infection, simultaneous loss of HBsAg and HDV RNA. NAP-based combination therapy (using REP 2139-Mg) achieves high rates of functional cure of HBV and HDV in the absence of therapy in previous clinical trials limited to patients without cirrhosis.

The Replicor compassionate access program (RCAP) provides early access to individuals which have HBV mono-infection, or HBV / HDV co-infection who have not responded to existing approved or experimental therapies and are in danger of progressing advanced liver disease or who have already progressed to decompensated cirrhosis. Examples of previous therapy includes but is not limited to pegylated interferon (pegIFN), bulevirtide or lonafarnib.

Participants with failure to previous therapy with compensated cirrhosis will receive REP 2139-Mg (250mg SC qW), TDF (300mg PO QD) and pegIFN (90ug SC qW) for 48 weeks. Participants with decompensated cirrhosis will receive REP 2139-Mg (250mg SC qW) and TDF (300mg PO QD).

During therapy, safety will be monitored weekly and efficacy every 4 weeks.

Patients who maintain HBsAg loss for 6 months following removal of REP 2139-Mg and pegIFN will be eligible for removal of the remaining TDF therapy.

Eligibility criteria: Inclusion Criteria:

1. Confirmed HBV or HBV / HDV co-infection.
2. Prior failure to pegIFN, bulevirtide, or lonafarnib or combinations thereof with advanced fibrosis or compensated cirrhosis.
3. Decompensated cirrhosis.
4. Willingness to utilize adequate contraception while being treated with REP 2139-Mg and for 6 months following the end of REP 2139-Mg treatment.

Exclusion Criteria:

1. Women with positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG).
2. Breast-feeding women.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Clichy
country: France
facility: AP-HP Hôpital Beaujon
city: Lille
country: France
facility: CHU Lille
city: Limoges
country: France
facility: CHU-Limoges
city: Marseille
country: France
facility: Hôpital Saint-Joseph
city: Montpellier
country: France
facility: Centre Hospitalier Universitaire de Montpellier
city: Montpellier
country: France
facility: CHU de Montpellier
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
city: Rennes
country: France
facility: CHU de Rennes
city: Toulouse
country: France
facility: CHU Rangueil, Université Toulouse 3
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Padua
country: Italy
facility: Padua University Hospital
city: Istanbul
country: Turkey
facility: Koç University Medical School
Study officials:
References:
citation: Vaillant A. REP 2139: Antiviral Mechanisms and Applications in Achieving Functional Control of HBV and HDV Infection. ACS Infect Dis. 2019 May 10;5(5):675-687. doi: 10.1021/acsinfecdis.8b00156. Epub 2018 Oct 5.
citation: Blanchet M, Sinnathamby V, Vaillant A, Labonte P. Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells. Antiviral Res. 2019 Apr;164:97-105. doi: 10.1016/j.antiviral.2019.02.009. Epub 2019 Feb 13.
citation: Boulon R, Blanchet M, Lemasson M, Vaillant A, Labonte P. Characterization of the antiviral effects of REP 2139 on the HBV lifecycle in vitro. Antiviral Res. 2020 Nov;183:104853. doi: 10.1016/j.antiviral.2020.104853. Epub 2020 Jun 23.
citation: Bazinet M, Pantea V, Cebotarescu V, Cojuhari L, Jimbei P, Albrecht J, Schmid P, Le Gal F, Gordien E, Krawczyk A, Mijocevic H, Karimzadeh H, Roggendorf M, Vaillant A. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial. Lancet Gastroenterol Hepatol. 2017 Dec;2(12):877-889. doi: 10.1016/S2468-1253(17)30288-1. Epub 2017 Sep 28.
citation: Bazinet M, Pantea V, Cebotarescu V, Cojuhari L, Jimbei P, Anderson M, Gersch J, Holzmayer V, Elsner C, Krawczyk A, Kuhns MC, Cloherty G, Dittmer U, Vaillant A. Persistent Control of Hepatitis B Virus and Hepatitis Delta Virus Infection Following REP 2139-Ca and Pegylated Interferon Therapy in Chronic Hepatitis B Virus/Hepatitis Delta Virus Coinfection. Hepatol Commun. 2020 Nov 13;5(2):189-202. doi: 10.1002/hep4.1633. eCollection 2021 Feb.
citation: Bazinet M, Pantea V, Placinta G, Moscalu I, Cebotarescu V, Cojuhari L, Jimbei P, Iarovoi L, Smesnoi V, Musteata T, Jucov A, Dittmer U, Krawczyk A, Vaillant A. Safety and Efficacy of 48 Weeks REP 2139 or REP 2165, Tenofovir Disoproxil, and Pegylated Interferon Alfa-2a in Patients With Chronic HBV Infection Naive to Nucleos(t)ide Therapy. Gastroenterology. 2020 Jun;158(8):2180-2194. doi: 10.1053/j.gastro.2020.02.058. Epub 2020 Mar 6.