Therapeutic Safety and Efficacy of REP 9AC (REP 2055) in HBV or HCV Infected Patients

NCT02646163 | Completed Phase 1

• 1 other identifier: REP 101
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

REP 9AC (REP 2055) is a nucleic acid polymer (NAP) with entry activity against hepatitis C virus and entry and post-entry antiviral activity against duck hepatitis B virus (DHBV) infection. REP 2055 has been shown to have potent prophylactic effect against HCV infection in vivo and potent therapeutic effect against established DHBV infection in vivo The REP 101 protocol is the first-in-man proof of concept study designed to investigate the safety and antiviral activity of REP 2055 administration in human patients with chronic HBV or HCV infection.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of REP 2055 treatment

  To record side effects, symptoms and adverse effects of REP 2055 exposure including laboratory test abnormalities.

  40 weeks (treatment)

Secondary Outcomes (1)

• Efficacy of REP 2055 treatment

  40 weeks (treatment) + 57 weeks (follow up)

Study Arms (1)

REP 2055

EXPERIMENTAL

Treatment with REP 2055

Drug: REP 2055

Interventions

REP 2055 DRUG

(First two patients) REP 2055 is administered once weekly by slow IV infusion in dose escalation from 100 to 1200mg until a grade 3 adverse event is observed not to exceed 40 weeks of dosing. (Subsequent patients) 400mg of REP 2055 is administered by slow IV infusion. First week of infusion to include daily dosing followed by twice weekly dosing for 40 weeks.

Also known as: REP 9AC

REP 2055

Eligibility Criteria

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

You may qualify if:

• HBsAg+ for at least 6 months prior to initiation of treatment.
• HBeAg+
• HBV titer \> 20000 copies/ml at start of treatment
• Treatment naïve
• HIV / hepatitis delta / HCV negative
• Compensated liver disease
• Ishak score ≤ 2
• Non cirrhotic
• No known active cytomegalovirus infection
• Willingness to utilize adequate contraception while being treated with REP 9AC (REP 2055) and for 6 months following the end of treatment
• Adequate venous access allowing weekly intravenous therapies and blood tests
• HCV positive for at least 6 months prior to initiation of treatment
• Genotype 3
• HCV titer \>3log IU/ml at start of treatment
• Treatment naïve

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
• Anti-HIV 1: 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%
• Alfa 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
• Platelets count \< 75,000 / cmm

Sponsors & Collaborators

• Replicor Inc.: lead

Study Sites (1)

Farabi General Hospital

Dhaka, 1213, Bangladesh

Location

Related Publications (5)

• Matsumura T, Hu Z, Kato T, Dreux M, Zhang YY, Imamura M, Hiraga N, Juteau JM, Cosset FL, Chayama K, Vaillant A, Liang TJ. Amphipathic DNA polymers inhibit hepatitis C virus infection by blocking viral entry. Gastroenterology. 2009 Aug;137(2):673-81. doi: 10.1053/j.gastro.2009.04.048. Epub 2009 Apr 23.

  PMID: 19394333 BACKGROUND

• 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

• 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

REP 2055

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

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: January 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: January 5, 2016

Record last verified: 2016-01

Locations

BA (1)