Boceprevir in HIV-HCV Coinfected Patients Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin
Information source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HCV Coinfection; HIV-1 Infection
Intervention: Boceprevir, Peg-interferon alfa 2b and Ribavirin (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) Official(s) and/or principal investigator(s): Isabelle Poizot-Martin, MD, Principal Investigator, Affiliation: Marseille University Hospital Eric Bellissant, MD, PhD, Study Chair, Affiliation: Rennes University Hospital
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.
Clinical Details
Official title: Pilot Study to Assess the Efficacy and Safety of Boceprevir, in Combination With Peg-Interferon Alfa and Ribavirin, in Patients With HCV/HIV Co-infection Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Sustained Virologic Response
Secondary outcome: HCV viral loadPredictive factors of Sustained virologic Response (SVR) HIV virologic endpoints Residual plasmatic concentration (Cres) of Ribavirin Hepatic factors: liver fibrosis score Alcohol consumption Evaluation of Pharmacokinetic parameters of anti-retroviral treatments Clinical and biological adverse events Number of participants classified by virologic failure type: non responder, relapser, null responder ITPA gene polymorphism CYP3A4 Polymorphism Maximal Concentration (Cmax) of antiretroviral treatments Area Under the Curve (AUC) of antiretrovirals Insulin resistance Metabolic syndrome Reasons and dates of treatment discontinuation Perceived symptoms French AIDS questionnaire of compliance Tobacco consumption Cannabis consumption Intravenous/nasal drugs consumption Residual Concentration (Cres) of atazanavir boosted or not by ritonavir Residual concentration (Cres) of ritonavir
Detailed description:
The majority of HIV/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.
Subjects enrolled in this trial will have many predictive factors of failure: HIV
co-infection, previous failure to Peg-Interferon/Ribavirin, HCV genotype 1 infection. One
study reported a SVR rate of 9% after re-treatment with Peg-Interferon/Ribavirin in such
patients. Another trial has shown a substantial increase of the response rate with a
tri-therapy in HCV mono-infected patients.
The investigators propose to carry out a multicentric, national, non-randomized phase II
trial in 80 patients.
The proportion of patients with F4 cirrhosis will have to be inferior to 50% of enrolled
subjects.
The number of null responders to a previous treatment (HCV RNA drop < 2 log10 at W12) and
without F4 cirrhosis will have to be lower or equal to 20.
The primary objective of the study is to estimate, in Genotype 1 - HCV/HIV co-infected
patients, non responders to a previous therapy with Peg-Interferon/Ribavirin, the rate of
SVR after 48 or 72 weeks of a three-drug regimen containing Peg-Interferon, Ribavirin and
Boceprevir according to the Virologic Response and to compare the SVR rate to a threshold
rate 20%, lowest rate to consider a therapeutic benefit in this population.
A pharmacokinetic sub-study including 30 patients will be performed to estimate
pharmacokinetic parameters of antiretroviral treatment (Atazanavir combined with Ritonavir,
Raltegravir, Tenofovir) in combination with anti HCV treatment at baseline and W8 and
pharmacokinetic parameters of Boceprevir at W8.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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).
- Subjects must be willing to give written informed consent for biological collection.
- Subjects must be willing to give written informed consent for treatment of genetics
data.
- Subjects affiliated or beneficiary to a medical insurance.
Exclusion Criteria:
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.
- Alcohol consumption which may disturb the study participation according to the
investigator
- Drug addiction which may disturb the study participation according to the
investigator. Patients taking part to a substitution program with methadone or
buprenorphine are allowed to be enrolled in the study.
Biological criteria:
• Haemoglobin < 12 g/dL (female) or < 13g/dL (male), Platelets < 90 000/mm3, Neutrophil
count < 1500/mm3, Renal failure defined as creatinine clearance < 50ml/min, Uncontrolled
thyroid function, HbA1c ≥ 7% in case of diabetes
Criteria related to study drugs
- Contra-indication to Ribavirin, interferon treatment including psychiatric
contra-indications.
- History of discontinuation for intolerance to anti-HCV treatment. Patients with a
history of discontinuation for intolerance, especially anaemia or leuconeutropenia,
and who were not treated with hematopoietic growth factor, are eligible
- Concomitant medication which may interfere with Boceprevir, atazanavir, ritonavir and
raltegravir pharmacokinetic
- St. John's-wort consumption
Locations and Contacts
CHU Sainte Marguerite, Marseille 13009, France
Additional Information
Starting date: May 2011
Last updated: October 10, 2014
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