Clinical trial NCT02726789
Conditions: Hepatitis B, Chronic
Keywords: nucleic acid polymer REP 2139 HBsAg hepatitis B
Sponsor: Replicor Inc.
Start date: 2012-10-01; Completion date: 2016-12-01
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The REP 201 protocol is a small exploratory study assessing the antiviral effects and tolerability of REP 2139-Ca when used with a full course of pegylated interferon (48 weeks) in treatment naive patients or in patients already receiving entecavir and continuing entecavir with treatment.

Detailed description:
Chronic hepatitis B is a long term condition caused by infection of the body with the hepatitis B virus (HBV). This infection often results in inflammation or scarring of the liver and can eventually lead to liver cirrhosis and liver failure. These infections are also one of the major causes of the development of hepatocellular carcinoma (liver cancer).

Although some drugs have been approved to treat chronic hepatitis B infections, they do not provide a complete cure except in rare cases (a cure generally means that a person loses the hepatitis B virus from the blood and the liver and develops a durable immunological control of subsequent HBV infection). However, these drugs do significantly decrease the risk of liver damage and liver cancer arising from the presence of a chronic liver infection by slowing or stopping the production of infectious virus. Thus the primary problem associated with currently available drugs is the lack of clearance of the virus from the hepatocytes which necessitates long term treatment with these drugs. There is clearly a need to identify new drugs that can benefit patients with chronic hepatitis B infections. Nucleic acid-based polymers (NAPs) are a new class of broad-spectrum antiviral compounds which act against HBV infection by blocking the release of the surface antigen protein (HBsAg) from infected hepatocytes.

Current interim data analysis from the REP 102 assessing the activity of the NAP REP 9AC' (REP 2139, given as a calcium chelate complex \[REP 2139-Ca\]) in patients with chronic HBV infection indicates the following:

1. REP 2139-Ca is generally well tolerated and patients tolerate short term combined treatment (13-26 weeks) of pegylated interferon and / or thymosin alpha
2. REP 2139-Ca has achieved serum HBsAg reduction or clearance 9 of 9 patients receiving combined therapy.
3. Appearance of substantial titers of serum anti-HBs occur with the addition of immunotherapy.
4. After all treatment is withdrawn, 8 / 9 patients achieved HBV DNA \< 116 copies / ml (LLOQ of the Roche Cobas platform) and sustained suppression of viremia (HBV DNA \< 1000 cpm, HBsAg \< 1 IU / ml) for a period of greater than 1 year was observed in four patients.

This exploratory study is designed to examine if REP 2139-Ca can be safely combined with a full course of pegylated interferon in treatment naive patients and in patients with previous and continuing therapy with entecavir and that similar antiviral effects can be observed as in the previous REP 101 and 102 protocols.

Arms: arm 1: Patients either treatment naive or with HBV DNA controlled with entecavir receive REP 2139-Ca in combination with pegylated interferon. Only patients receiving entecavir at enrollment continue to receive entecavir during treatment in the study.
Interventions: intervention 1: REP 2139-Ca intervention 2: pegylated interferon intervention 3: entecavir
Intervention descriptions: intervention 1: the nucleic acid polymer REP 2139 formulated as a calcium chelate complex intervention 2: immunotherapy intervention 3: local generic entecavir

Protocol documents: