Replicor Compassionate Access Program

Hepatocellular Carcinoma Clinical Trial

— RCAP  

Official title:

Compassionate Use Access to REP 2139-Mg for the Treatment of Chronic HBV Infection or Chronic HBV / HDV Co-infection

Clinical Trial Details — Status: Available

Administrative data

• NCT number: NCT05683548
• Other study ID #: RCAP
• Status: Available

Study information

• Verified date: January 2023
• Source: Replicor Inc.
• Contact: Andrew Vaillant, Ph.D.
• Phone: +1 514 733-1998
• Email: availlant[@]replicor.com
• Is FDA regulated: No
• Study type: Expanded Access

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Available
• Enrollment: 0
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Ascites
• Ascites Hepatic
• Cirrhosis, Liver
• Decompensated Cirrhosis
• Esophageal and Gastric Varices
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis D
• Hepatocellular Carcinoma
• Liver Cirrhosis
• Varices, Esophageal
• Viral Hepatitis B
• Viral Hepatitis D

Intervention

Drug:
• REP 2139-Mg
REP 2139-Mg is the magnesium chelate complex of REP 2139
• Tenofovir Disoproxil Fumarate

• Pegylated interferon alpha2a

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna
France	AP-HP Hôpital Beaujon	Clichy
France	CHU Lille	Lille
France	CHU-Limoges	Limoges
France	Hôpital Saint-Joseph	Marseille
France	Centre Hospitalier Universitaire de Montpellier	Montpellier
France	CHU de Montpellier	Montpellier
France	Centre Hospitalier de Perpignan	Perpignan
France	CHU de Rennes	Rennes
France	CHU Rangueil, Université Toulouse 3	Toulouse
Israel	Soroka Medical Center	Be'er Sheva
Italy	Padua University Hospital	Padua
Turkey	Koç University Medical School	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Replicor Inc.

Countries where clinical trial is conducted

Austria,  France,  Israel,  Italy,  Turkey, 

References & Publications (6)

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. Erratum In: Lancet Gastroenterol Hepatol. 2018 Jan;3(1):e1. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

External Links

•   Interaction of NAPs with HDAg
•   Repicor Inc.