Boceprevir in HIV-HCV Coinfected Patients Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin

NCT01335529 | Completed Phase 2 DMC

• 1 other identifier: ANRS HC27 BOCEPREVIH
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

The majority of Human immunodeficiency Virus (HIV)/Hepatitis C Virus (HCV) co-infected patients are non responders after 48 weeks of the current standard-of-care with Peg-Interferon/Ribavirin. The results of re-treatment are disappointing. The addition of Boceprevir to the current standard-of-care has been shown to increase the efficacy of therapy in HCV mono-infected patients previously treated with a bi-therapy. Knowing that HIV/HCV co-infected patients are subject to more rapid hepatic fibrosis as well as to increased risks of cirrhosis, end-stage liver disease and hepatocellular carcinoma, it is important to improve the response rate of the re-treatment of hepatitis C in these patients. The aim of this pilot study is to evaluate the efficacy and safety of Boceprevir in combination with Peg-Interferon alfa 2b plus ribavirin, in patients co-infected with HIV and chronic genotype 1 HCV, and previously treated with Peg-Interferon/Ribavirin. 80 subjects will be enrolled. The primary endpoint will be the Sustained Virologic Response (SVR) defined as undetectable HCV-RNA at Week 24 after the end of therapy.

Conditions

HCV Coinfection; HIV-1 Infection

Keywords

HCV infection; HIV-1 infection

Outcome Measures

Primary Outcomes (1)

• Sustained Virologic Response

  HCV-RNA measured 24 weeks after the end of the HCV treatment (W72 or W96)

  Week 72 or Week 96 (W72 or W96)

Secondary Outcomes (23)

• HCV viral load

  W4, W8, W12, W16, W28, W36 and at treatment completion at W48/72

• Predictive factors of Sustained virologic Response (SVR)

  Baseline

• HIV virologic endpoints

  W4, W8, W12, W16, W20, W24, W28, W32, W36, W40, W44, W48, W60, W72 and W84, W96 if treatment duration is 72 weeks

• Residual plasmatic concentration (Cres) of Ribavirin

  W4 and W8

• Hepatic factors: liver fibrosis score

  Screen, W4, W8, W16, W28, W48, W72, W96.

Study Arms (1)

Boceprevir, PegIFN alfa 2b, Ribavirin

EXPERIMENTAL

Standard Treatment : * Peg-Interferon (PegIFN) alfa 2b by subcutaneous injection 1,5 µg/kg/week * Ribavirin capsules 200mg: dosage delivered in weight categories (\< 65 kg: 800 mg ; 65-80 kg: 1000 mg; 81-105 kg: 1200mg; \> 105 kg: 1400mg) Three-drug-regimen: * Peg-Interferon alfa 2b by subcutaneous injection 1,5 µg/kg/week * Ribavirin capsules 200mg: dosage delivered in weight categories like in standard treatment * Boceprevir tablets 200mg: 800 mg 3 times a day (2400 mg/j) with food

Drug: Boceprevir, Peg-interferon alfa 2b and Ribavirin

Interventions

Boceprevir, Peg-interferon alfa 2b and Ribavirin DRUG

* Screen period from Week-8 * Standard treatment from day 0 to week 4 (W4) * Three-drug-regimen (Boceprevir introduction) from W4 to W8 * HCV RNA determination at W8 determines treatment group and participation duration: * If undetectable HCV RNA at W8, it is a complete virological response: 3 drug-regimen is continued until W48, then there is a follow-up period up to W72 and SVR analysis, * If HCV RNA ≤ 1000IU/mL at W8, it is an incomplete virological response. The 3-drug-regimen is continued until W72, when another analysis is done.

Also known as: ViraferonPeg, Rebetol

Boceprevir, PegIFN alfa 2b, Ribavirin

Eligibility Criteria

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

You may qualify if:

• Adult ≥18 years
• HIV-1 infection
• Infection to genotype 1 HCV only
• Patients must have received at least 12 weeks of treatment with Peg-Interferon alfa 2a ≥ 135 µg / once weekly or Peg-Interferon alfa 2b ≥ 1,0 µg/kg/ once weekly + Ribavirin ≥ 600 mg daily and must have failed to treatment.
• Anti-HCV treatment stopped for at least 6 months
• Patients must be already treated at screen since at least 3 months with a stable combination of antiretroviral treatment as following:
• Either tenofovir - emtricitabine, and atazanavir in combination with ritonavir
• Or tenofovir - emtricitabine, and raltegravir
• If patients cannot receive neither of the two antiretroviral regimens proposed, for virologic, safety or toxicity reasons, patients could receive any effective antiretroviral therapy including : tenofovir, emtricitabine, lamivudine, atazanavir alone or in combination with ritonavir, raltegravir, abacavir. These patients are not allowed to take part in the pharmacokinetic sub-study.
• CD4 \> 200/mm3 et \>15%, at screen
• HIV-RNA \< 50 copies/ml since at least 6 months at screen
• ≥ 40 Kg and ≤ 125 Kg
• Patients with any fibrosis grade. Proportion of F4 subjects should not excess 50% of the overall subjects.
• Male and female subjects must agree to use acceptable methods of contraception 1 month prior to starting the study treatment and to continue until 7 months after the last doses of study drugs for male subjects and their partner(s), 4 months for female subjects.
• Subjects must be willing to give written informed consent for principal study (signed at least at screen visit and prior to any study investigation)and + for the pharmacokinetic sub-study (for the concerned centers).

You may not qualify if:

• History:
• Patients with cirrhosis (F4) and nul responders to prior treatment
• Cirrhosis classified Child-Pugh B or C or history of decompensated cirrhosis of the liver. If Child A classification, significant varicose veins (grade 2 or 3) observed with a fibroscopy realized for \< 3 years.
• History of ocular neuritis, retinal disorders, transplant
• Opportunistic infections (classification C), active or occurred within the 6 months prior to baseline.
• History of neoplasia within the last 5 years, except cutaneous basocellular carcinoma, recovering Kaposi's sarcoma, in situ cervical or anal canal cancer.
• Current condition:
• Co-infection with Hepatitis B virus
• Pregnancy and lactation
• Cardiac or severe pulmonary disease
• Untreated dysthyroidism
• Autoimmune disease contraindicating to an interferon treatment
• Severe haemoglobinopathies
• Any condition needing a systemic corticotherapy or an immunosuppressive treatment
• Evolutive current malignancy, including hepatocarcinoma which should be specifically controlled prior to baseline.

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Rennes University Hospital: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

CHU Sainte Marguerite

Marseille, 13009, France

Location

Related Publications (1)

• Poizot-Martin I, Bellissant E, Garraffo R, Colson P, Piroth L, Solas C, Renault A, Bourliere M, Halfon P, Ghosn J, Alric L, Naqvi A, Carrieri P, Molina JM; ANRS HC27 BOCEPREVIH Study Group. Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study. HIV Clin Trials. 2016 Mar;17(2):63-71. doi: 10.1080/15284336.2015.1135553. Epub 2016 Feb 11.

  PMID: 27077673 DERIVED

MeSH Terms

Conditions

Hepatitis C

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; Ribavirin; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Isabelle Poizot-Martin, MD

  University Hospital, Marseille

  PRINCIPAL INVESTIGATOR

• Eric Bellissant, MD, PhD

  Rennes University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2011
• First Posted: April 14, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: October 13, 2014

Record last verified: 2014-10

Locations

FR (1)