Hepatitis B, Chronic
Conditions
Keywords
nucleic acid polymer REP 2139 HBsAg hepatitis B
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 After all treatment is withdrawn, 8 / 9 patients achieved HBV DNA \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.
Interventions
DRUGREP 2139-Ca
the nucleic acid polymer REP 2139 formulated as a calcium chelate complex
DRUGpegylated interferon
immunotherapy
DRUGentecavir
local generic entecavir
Sponsors
Replicor Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 55 * HBsAg+ * Anti-HBs negative * Patients currently receiving nucleoside based HBV polymerase inhibitors may be included in the study at the discretion of the Principle Investigator. * HIV / hepatitis C / hepatitis delta virus negative * Fibrosis with compensation (as determined by Fibroscan and liver enzymes) * Non cirrhotic * No known active cytomegalovirus infection * Willingness to utilize adequate contraception while being treated with REP 9AC' and for 6 months following the end of treatment * Adequate venous access allowing weekly intravenous therapies and blood tests
Exclusion criteria
* Evidence of cardiovascular disease * Autoimmune hepatitis * Presence of Wilson's disease * Presence of severe NAFLD * Evidence of any other co-existent liver disease * Anti-nuclear antibody positive * Ultrasonograph of hepato-biliary system: positive for cirrhosis of liver * A history of ascites, hepatic encephalopathy or variceal hemorrhage * Body weight \> 100 kg * Platelet count \< 75,000, polymorphonuclear cell count \< 1,500 or hematocrit \< 33% * alpha feto protein \> 100 ng/ml or the presence of a hepatic mass suggestive of hepatocellular carcinoma . * Bilirubin \> 2.5 mg/dl * Creatinine \> 1.5 mg/dl * Platelet count \< 75,000 / cmm * Serum albumin \< 35 mg/ml * Poorly controlled diabetes mellitus * Another serious medical disorder * A serious psychiatric disorder * Uncontrolled hypertension * A history of alcohol abuse within the last year * The use of illicit drugs within the past two years * Inability to provide informed consent * Positive pregnancy test * Breastfeeding * Inability or unwillingness to provide weekly blood samples * Poor venous access making IV infusion too difficult
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing Treatment Emergent Laboratory Test Abnormalities or Adverse Events. | 48 weeks (treatment) | To record side effects, symptoms and adverse effects of exposure to REP 2139-Ca when combined pegylated interferon. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing Reductions in Serum HBsAg | 48 weeks (treatment) | To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBsAg. |
| Number of Patients Experiencing Reductions in Serum HBV DNA | 48 weeks (treatment) | To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBV DNA. |
| Number of Patients Experiencing Serum Anti-HBs > 10 mIU / ml | 48 weeks (treatment) | To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on anti-HBsAg antibody titer. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Participants receive REP 2139-Ca in combination with pegylated interferon. Participants included in this study are either entecavir naive OR have prior exposure to entecavir.
REP 2139-Ca: the nucleic acid polymer REP 2139 formulated as a calcium chelate complex
pegylated interferon: immunotherapy
Participants receiving entecavir at the start of therapy continue to receive entecavir during experimental therapy. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Experimental |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 27.6 years STANDARD_DEVIATION 3.14 |
| Region of Enrollment Bangladesh | 5 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Number of Patients Experiencing Treatment Emergent Laboratory Test Abnormalities or Adverse Events.
To record side effects, symptoms and adverse effects of exposure to REP 2139-Ca when combined pegylated interferon.
Time frame: 48 weeks (treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental | Number of Patients Experiencing Treatment Emergent Laboratory Test Abnormalities or Adverse Events. | 5 Participants |
Secondary
Number of Patients Experiencing Reductions in Serum HBsAg
To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBsAg.
Time frame: 48 weeks (treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental | Number of Patients Experiencing Reductions in Serum HBsAg | 5 Participants |
Secondary
Number of Patients Experiencing Reductions in Serum HBV DNA
To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBV DNA.
Time frame: 48 weeks (treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental | Number of Patients Experiencing Reductions in Serum HBV DNA | 5 Participants |
Secondary
Number of Patients Experiencing Serum Anti-HBs > 10 mIU / ml
To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on anti-HBsAg antibody titer.
Time frame: 48 weeks (treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental | Number of Patients Experiencing Serum Anti-HBs > 10 mIU / ml | 5 Participants |