Chronic HBV Infection (HBeAg Negative) Clinical Trial
Official title:
A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection
| Verified date | February 2017 |
| Source | Replicor Inc. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to
clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV
infected ducks) and in human patients and to act synergistically with immunotherapeutic
agents such as pegylated interferon-alpha 2a or thymosin alpha-1 to restore host
immunological control of HBV infection.
HBsAg is an essential component of the hepatitis D virus (HDV), therefore the direct action
of REP 2139-Ca in removing serum HBsAg and its synergistic effect with pegylated
interferon-alpha 2a is expected to have a significant antiviral effect against HDV infection.
This study will examine the safety and efficacy of REP 2139-Ca therapy when used in
combination with pegylated interferon alpha-2a in patients with HBV / HDV co-infection.
The primary hypothesis to be tested is that this combined dosing regimen is safe and well
tolerated in patients with HBV / HDV co-infection which will be assessed by examining the
number of patients with adverse events (including reported symptoms and laboratory
abnormalities).
The secondary hypothesis to be tested is that this combined dosing regimen will have an
antiviral effect against HBV / HDV co-infection in these patients which will be assessed by
examining the following outcomes:
1. The number of patients with reductions in serum HBsAg.
2. The number of patients with reductions in serum HDAg and HDV RNA
3. The number of patients that experience a sustained antiviral response after treatment is
stopped (reductions in serum HBV DNA and HDV RNA).
The secondary hypothesis to be tested is that this combination approach can have an effective
| Status | Completed |
| Enrollment | 12 |
| Est. completion date | May 2017 |
| Est. primary completion date | November 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 55 Years |
| Eligibility |
Inclusion Criteria: - Age between 18 and 55 years - HBsAg > 1000 IU / ml - HDAg+ - HDV RNA + - No detectable antibodies to HIV, HCV or CMV. - Non cirrhotic - Willingness to utilize adequate contraception while being treated with REP 213-Ca and for 6 months following the end of treatment - Adequate venous access allowing weekly intravenous therapies and blood tests - Body Mass Index (BMI) = 18 kg/m2 and = 25 kg/m2 Exclusion Criteria: - Evidence of cardiovascular disease - Evidence of autoimmune hepatitis - Presence of Wilson's disease - Presence of severe NAFLD - Evidence of any other co-existent liver disease - ANA (anti-nuclear antibody) positive - Fibroscan and Fibromax showing evidence of advanced cirrhosis. - Any history of ascites, hepatic encephalopathy or variceal hemorrhage - Body weight > 100 kg - Platelet count < 90,000, PMN count < 1,500 or HCT < 33% - Evidence of significant heavy metal load in whole blood. - AFP > 100 ng/ml or the presence of a hepatic mass suggestive of HCC - Bilirubin above the normal range - ALT > 5x ULN - Creatinine > 1.5 mg/dl - Serum albumin < 35 mg/ml - The presence of diabetes (whether controlled or uncontrolled) - Another serious medical disorder - A serious psychiatric disorder - Evidence of 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 - Inability or unwillingness to provide weekly blood samples - Poor venous access making IV infusion too difficult - Patient not willing to come every week to receive therapy |
| Country | Name | City | State |
|---|---|---|---|
| Moldova, Republic of | Infectious Clinical Hospital ( n.a. Toma Ciorba) | Chisinau |
| Lead Sponsor | Collaborator |
|---|---|
| Replicor Inc. |
Moldova, Republic of,
Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers inhibit duck hepatitis B virus infection in vitro. Antimicrob Agents Chemother. 2013 Nov;57(11):5291-8. doi: 10.1128/AAC.01003-13. Epub 2013 Aug 12. — View Citation
Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers prevent the establishment of duck hepatitis B virus infection in vivo. Antimicrob Agents Chemother. 2013 Nov;57(11):5299-306. doi: 10.1128/AAC.01005-13. Epub 2013 Aug 12. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Number of patients experiencing a treatment-related adverse event. | Will examine the hypothesis that combined REP 2139-Ca / Pegasys(TM) treatment is safe and well tolerated in patients with HBV / HDV co-infection | Every week for 63 weeks. | |
| Secondary | Number of patients with reduction of serum HBsAg. | Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection. | Every two weeks for 63 weeks (treatment duration) + 24 weeks (follow-up) | |
| Secondary | Number of patients with reduced serum HDV antigen / HDV RNA | Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection. | Every two weeks for 63 weeks (treatment duration) + 24 weeks followup | |
| Secondary | Number of patients with controlled HBV / HDV infection following treatment | Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection. | 24 weeks follow up (after completion of 63 weeks of treatment) |