REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection

NCT02233075 | Completed Phase 2

• 1 other identifier: REP 301
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.The number of patients with reductions in serum HBsAg.
2. 2.The number of patients with reductions in serum HDAg and HDV RNA
3. 3.The number of patients that experience a sustained antiviral response after treatment is stopped (reductions in serum HBV DNA and HDV RNA).

Conditions

Chronic HBV Infection (HBeAg Negative)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Number of patients with reduction of serum HBsAg.

  Every two weeks for 63 weeks (treatment duration) + 24 weeks (follow-up)

• Number of patients with reduced serum HDV antigen / HDV RNA

  Every two weeks for 63 weeks (treatment duration) + 24 weeks followup

• Number of patients with controlled HBV / HDV infection following treatment

  24 weeks follow up (after completion of 63 weeks of treatment)

Study Arms (1)

REP 2139-Ca + Pegasys (TM)

EXPERIMENTAL

REP 2139-Ca 500 mg QW for 15 weeks followed by REP 2139-Ca 250mg QW + Pegasys(TM) 180ug QW for 15 weeks followed by Pegasys(TM) 180ug QW for 33 weeks.

Drug: REP 2139-Ca + Pegasys (TM)

Interventions

REP 2139-Ca + Pegasys (TM) DRUG

15 weeks of REP 2139-Ca (500mg QW IV) followed by: 15 weeks of REP 2139-Ca (250mg QW IV) + Pegasys(TM) (180 ug QW SC) followed by: 33 weeks of Pegasys(TM) (180 ug QW SC)

Also known as: Pegasys(TM) = pegylated interferon alpha-2a

REP 2139-Ca + Pegasys (TM)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Replicor Inc.: lead

Study Sites (1)

Infectious Clinical Hospital ( n.a. Toma Ciorba)

Chisinau, 2004, Moldova

Location

Related Publications (4)

• 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.

  PMID: 23939902 BACKGROUND

• 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.

  PMID: 23939904 BACKGROUND

• 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.

  PMID: 33553968 DERIVED

• 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.

  PMID: 28964701 DERIVED

MeSH Terms

Interventions

peginterferon alfa-2a

Study Officials

• Victor Pantea, MD

  Infectious Diseases Department, State University of Medicine and Pharmacy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2014
• First Posted: September 8, 2014
• Study Start: September 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: May 1, 2017
• Last Updated: September 28, 2017

Record last verified: 2017-02

Locations

MO (1)