A Pilot Study of Boceprevir for the Treatment of Genotype 6 HCV

NCT01949168 | Unknown Phase 2

• 1 other identifier: HCV-6 study
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the antiviral efficacy of Boceprevir-based therapy for the treatment of genotype 6 chronic hepatitis C infection. Boceprevir has recently been approved for the treatment of genotype 1 chronic hepatitis C infection. Recent in vitro studies suggest similar efficacy against genotype 6 chronic hepatitis C infection. The investigators therefore hypothesise that: i) Boceprevir is a potent inhibitor of genotype 6 hepatitis C replication in vivo. ii) Boceprevir in combination with pegylated interferon-alpha and ribavirin for 24 weeks will cure a high proportion of patients chronically infected with genotype 6 chronic hepatitis C infection.

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Early viral kinetics

  Determined by plasma HCV RNA quantification at frequent time points - baseline, day 1, 2, 3, 4 and 5

  Day 5

Secondary Outcomes (5)

• Rates of virological response

  Day 3, 5, week 2, week 4, week 12 and end of treatment (week 24 or week 48)

• Number of patients eligible for Response Guided Therapy

  Week 4 and week 20

• Rates of virological breakthrough

  Week 4, week 20, week 24, week 48, week 60

• Rates of SVR12 and relapse

  Week 48 and Week 60

• Rates of anaemia on treatment

  Day 0, 1, 2, 3, 4, 5, then monthly up to week 48 of treatment

Study Arms (3)

Boceprevir triple therapy with 5-day lead in

ACTIVE COMPARATOR

Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets) for 5 days, followed by boceprevir plus • Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection plus • Rebetol® (ribavirin), 1000/1200mg, by mouth daily for 24 weeks. In patients who achieve an undetectable plasma HCV RNA level at week 4 of triple therapy (week 5 from baseline), and maintain an undetectable plasma HCV RNA at week 20 of triple therapy (week 21 from baseline), treatment will stop at week 25. Patients who have a detectable plasma HCV RNA at week 4 of triple therapy, but an undetectable plasma HCV RNA at week 20, will continue a with follow-on peginterferon-α-2b plus ribavirin for a further 23 weeks (stopping at week 48).

Drug: Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets); Drug: Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection; Drug: Rebetol® (ribavirin), 1000/1200mg by mouth daily

Boceprevir triple therapy

ACTIVE COMPARATOR

Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets) plus Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection and Rebetol® (ribavirin), 1000/1200mg, by mouth daily for 24 weeks. In patients who achieve an undetectable plasma HCV RNA level at week 4 of triple therapy, and maintain an undetectable plasma HCV RNA at week 20 of triple therapy, treatment will stop at week 24. Patients who have a detectable plasma HCV RNA at week 4 of triple therapy, but an undetectable plasma HCV RNA at week 20, will continue a with follow-on peginterferon-α-2b plus ribavirin for a further 24 weeks (stopping at week 48).

Drug: Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets); Drug: Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection; Drug: Rebetol® (ribavirin), 1000/1200mg by mouth daily

Standard of Care

ACTIVE COMPARATOR

48 weeks of Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection and Rebetol® (ribavirin), 1000/1200mg by mouth daily (200mg tablets)

Drug: Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection; Drug: Rebetol® (ribavirin), 1000/1200mg by mouth daily

Interventions

Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets) DRUG

Boceprevir triple therapy; Boceprevir triple therapy with 5-day lead in

Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection DRUG

Boceprevir triple therapy; Boceprevir triple therapy with 5-day lead in; Standard of Care

Rebetol® (ribavirin), 1000/1200mg by mouth daily DRUG

Boceprevir triple therapy; Boceprevir triple therapy with 5-day lead in; Standard of Care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, at least 18 years of age
• Asian background
• HCV treatment-naïve.
• Chronic HCV infection is defined as one of the following:
• Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before Screening, and positive for HCV RNA and anti-HCVAb at the time of Screening; or
• Positive for anti-HCV Ab and HCV RNA at the time of Screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of chronic hepatitis C disease).
• Screening laboratory result indicating HCV genotype 6-infection (HCV-6).
• Plasma HCV RNA level \> 10,000 IU/mL at Screening.
• IL28B C/C genotype (rs12979860)
• Per local standard practice, documented results of one of the following:
• A liver biopsy within 24 months prior to or during screening demonstrating the absence of cirrhosis, e.g., a METAVIR Score of 3 or less, Ishak score of 4 or less; or
• A screening FibroTest score of ≤ 0.72 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 2; or
• A screening FibroScan result of \< 9.6 kPa.
• Subjects with a non-qualifying Fibrotest/APRI or Fibroscan result may only be enrolled if they have a qualifying liver biopsy preformed within 24 months prior to or during screening.
• Candidate for PEG/RBV therapy

You may not qualify if:

• Non-genotype 6 HCV infection, or evidence of mixed genotype HCV infection
• IL28B C/T or T/T polymorphism (rs12979860)
• Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of \>3 or Ishak score of \> 4.
• Exceed defined thresholds for key laboratory parameters at Screening.
• Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug.
• Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human immunodeficiency virus antibody (HIV Ab).
• Diagnosis of autoimmune disease, decompensated liver, disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed
• Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study.
• Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment, as defined by the product label.

Sponsors & Collaborators

• St Vincent's Hospital Melbourne: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

St Vincent's Hospital

Fitzroy, Victoria, 3065, Australia

Location

Western Hospital

Footscray, Victoria, 3011, Australia

Location

Related Publications (7)

• Sievert W, Altraif I, Razavi HA, Abdo A, Ahmed EA, Alomair A, Amarapurkar D, Chen CH, Dou X, El Khayat H, Elshazly M, Esmat G, Guan R, Han KH, Koike K, Largen A, McCaughan G, Mogawer S, Monis A, Nawaz A, Piratvisuth T, Sanai FM, Sharara AI, Sibbel S, Sood A, Suh DJ, Wallace C, Young K, Negro F. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int. 2011 Jul;31 Suppl 2:61-80. doi: 10.1111/j.1478-3231.2011.02540.x.

  PMID: 21651703 BACKGROUND

• Dev AT, McCaw R, Sundararajan V, Bowden S, Sievert W. Southeast Asian patients with chronic hepatitis C: the impact of novel genotypes and race on treatment outcome. Hepatology. 2002 Nov;36(5):1259-65. doi: 10.1053/jhep.2002.36781.

  PMID: 12395338 BACKGROUND

• Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74. doi: 10.1002/hep.22759. No abstract available.

  PMID: 19330875 BACKGROUND

• Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1195-206. doi: 10.1056/NEJMoa1010494.

  PMID: 21449783 BACKGROUND

• Bathgate A. Boceprevir for previously treated chronic hepatitis C virus genotype 1 infection. J R Coll Physicians Edinb. 2011 Jun;41(2):122-3. doi: 10.4997/JRCPE.2011.222. No abstract available.

  PMID: 21677916 BACKGROUND

• Silva MO, Treitel M, Graham DJ, Curry S, Frontera MJ, McMonagle P, Gupta S, Hughes E, Chase R, Lahser F, Barnard RJ, Howe AY, Howe JA. Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3. J Hepatol. 2013 Jul;59(1):31-7. doi: 10.1016/j.jhep.2013.02.018. Epub 2013 Feb 27.

  PMID: 23454058 BACKGROUND

• Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401. doi: 10.1038/nature08309. Epub 2009 Aug 16.

  PMID: 19684573 BACKGROUND

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Alexander Thompson, MBBS

  St Vincent's Hospital Melbourne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hepatology Research

Study Record Dates

• First Submitted: September 4, 2013
• First Posted: September 24, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2015
• Last Updated: September 24, 2013

Record last verified: 2013-09

Locations

AU (4)