Therapeutic Safety and Efficacy of REP 2139 (REP 9AC') in HBV Infected Patients

NCT02646189 | Completed Phase 1

• 1 other identifier: REP 102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

REP 9AC (REP 2055) is a nucleic acid polymer (NAP) with entry and post-entry antiviral activity against duck hepatitis B virus (DHBV) infection. REP 2055 has been shown to have potent therapeutic effect against established DHBV infection in vivo REP 2055 was additionally shown to have significant antiviral effects in patients with chronic HBV infection in the previous REP 101 study. REP 2139 is a version of REP 2055 designed for improved administration tolerability and stability. The safety and antiviral activity REP 2139, first in monotherapy and then in combination with immunotherapy in patients with chronic HBV infection will be assessed in the REP 102 protocol.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of REP 2139-Ca + immunotherapy

  To record side effects, symptoms and adverse effects of exposure to REP 2139-Ca in monotherapy and when combined with Zadaxin and / or Pegasys.

  40 weeks (treatment)

Secondary Outcomes (1)

• Efficacy of REP 2139-Ca + immunotherapy

  40 weeks (treatment) + 52 weeks (follow up)

Study Arms (1)

REP 2139-Ca + immunotherapy

EXPERIMENTAL

REP 2139-Ca is the calcium chelate complex formulation of REP 2139. Zadaxin is thymosin alpha 1 Pegasys is pegylated interferon alpha 2a Patients initially receiving REP 2139-Ca with no Grade 3 adverse events at week 20 are eligible to transition to combination therapy with Zadaxin if serum HBV DNA is \> 2000 copies / ml. After 10 weeks of REP 2139-Ca / Zadaxin combination therapy, patients not experiencing a measurable improvement in serum antiviral response can further transition to combination therapy with REP 2139-Ca and Pegasys.

Drug: REP 2139-Ca; Drug: Zadaxin; Drug: Pegasys

Interventions

REP 2139-Ca DRUG

REP 2139-Ca is administered weekly at 250 or 500mg doses by slow IV infusion.

REP 2139-Ca + immunotherapy

Zadaxin DRUG

Zadaxin is administered twice weekly (1.6mg) by subcutaneous injection

Also known as: thymosin alpha 1

REP 2139-Ca + immunotherapy

Pegasys DRUG

Pegasys in administered once weekly by subcutaneous injection with dose escalation to 180ug / week.

Also known as: pegylated interferon alpha-2a

REP 2139-Ca + immunotherapy

Eligibility Criteria

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

You may qualify if:

• HBsAg+
• Anti-HBs negative
• HBV titer \> 1x10\^7 copies / ml
• Treatment naïve
• HIV / HCV / 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

You may not qualify if:

• 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
• Evidence of liver cirrhosis
• 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

Sponsors & Collaborators

• Replicor Inc.: lead

Study Sites (1)

Farabi General Hospital

Dhaka, 1213, Bangladesh

Location

Related Publications (10)

• 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

• Noordeen F, Scougall CA, Grosse A, Qiao Q, Ajilian BB, Reaiche-Miller G, Finnie J, Werner M, Broering R, Schlaak JF, Vaillant A, Jilbert AR. Therapeutic Antiviral Effect of the Nucleic Acid Polymer REP 2055 against Persistent Duck Hepatitis B Virus Infection. PLoS One. 2015 Nov 11;10(11):e0140909. doi: 10.1371/journal.pone.0140909. eCollection 2015.

  PMID: 26560490 BACKGROUND

• Jiang YF, Ma ZH, Zhao PW, Pan Y, Liu YY, Feng JY, Niu JQ. Effect of thymosin-alpha(1) on T-helper 1 cell and T-helper 2 cell cytokine synthesis in patients with hepatitis B virus e antigen-positive chronic hepatitis B. J Int Med Res. 2010;38(6):2053-62. doi: 10.1177/147323001003800620.

  PMID: 21227010 BACKGROUND

• Iino S, Toyota J, Kumada H, Kiyosawa K, Kakumu S, Sata M, Suzuki H, Martins EB. The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic hepatitis B; results from a randomized clinical trial. J Viral Hepat. 2005 May;12(3):300-6. doi: 10.1111/j.1365-2893.2005.00633.x.

  PMID: 15850471 BACKGROUND

• Andreone P, Cursaro C, Gramenzi A, Zavagliz C, Rezakovic I, Altomare E, Severini R, Franzone JS, Albano O, Ideo G, Bernardi M, Gasbarrini G. A randomized controlled trial of thymosin-alpha1 versus interferon alfa treatment in patients with hepatitis B e antigen antibody--and hepatitis B virus DNA--positive chronic hepatitis B. Hepatology. 1996 Oct;24(4):774-7. doi: 10.1002/hep.510240404.

  PMID: 8855175 BACKGROUND

• Zhuang L, You J, Tang BZ, Ding SY, Yan KH, Peng D, Zhang YM, Zhang L. Preliminary results of Thymosin-a1 versus interferon-alpha-treatment in patients with HBeAg negative and serum HBV DNA positive chronic hepatitis B. World J Gastroenterol. 2001 Jun;7(3):407-10. doi: 10.3748/wjg.v7.i3.407. No abstract available.

  PMID: 11819800 BACKGROUND

• You J, Zhuang L, Cheng HY, Yan SM, Yu L, Huang JH, Tang BZ, Huang ML, Ma YL, Chongsuvivatwong V, Sriplung H, Geater A, Qiao YW, Wu RX. Efficacy of thymosin alpha-1 and interferon alpha in treatment of chronic viral hepatitis B: a randomized controlled study. World J Gastroenterol. 2006 Nov 7;12(41):6715-21. doi: 10.3748/wjg.v12.i41.6715.

  PMID: 17075991 BACKGROUND

• Usman Z, Mijocevic H, Karimzadeh H, Daumer M, Al-Mathab M, Bazinet M, Frishman D, Vaillant A, Roggendorf M. Kinetics of hepatitis B surface antigen quasispecies during REP 2139-Ca therapy in HBeAg-positive chronic HBV infection. J Viral Hepat. 2019 Dec;26(12):1454-1464. doi: 10.1111/jvh.13180. Epub 2019 Aug 13.

  PMID: 31323705 DERIVED

• Al-Mahtab M, Bazinet M, Vaillant A. Safety and Efficacy of Nucleic Acid Polymers in Monotherapy and Combined with Immunotherapy in Treatment-Naive Bangladeshi Patients with HBeAg+ Chronic Hepatitis B Infection. PLoS One. 2016 Jun 3;11(6):e0156667. doi: 10.1371/journal.pone.0156667. eCollection 2016.

  PMID: 27257978 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Thymalfasin; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thymosin; Thymus Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Proteins

Study Officials

• Mamun Al-Mahtab, MD

  Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2016
• First Posted: January 5, 2016
• Study Start: August 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: January 5, 2016

Record last verified: 2016-01

Locations

BA (1)