Replicor Compassionate Access Program

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Viral Hepatitis B, Viral Hepatitis D, Cirrhosis, Liver, Decompensated Cirrhosis, Ascites Hepatic, Varices, Esophageal, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: REP 2139-Mg
* Drug: Tenofovir Disoproxil Fumarate
* Drug: Pegylated interferon alpha2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HBV or HBV / HDV co-infection. Prior failure to pegIFN, bulevirtide, or lonafarnib or combinations thereof with advanced fibrosis or compensated cirrhosis. Decompensated cirrhosis. 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: Women with positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG). Breast-feeding women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: REP 2139-Mg|REP 2139-Mg is the magnesium chelate complex of REP 2139|
|Drug: Tenofovir Disoproxil Fumarate|nan|
|Drug: Pegylated interferon alpha2a|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nucleic acid polymer, REP 2139-Mg, HBV, HDV, cirrhosis, functional cure