COINFECTION, Hepatitis C, HIV Infections
Conditions
Keywords
HCV, HIV, Coinfection
Brief summary
The primary objective of this study is to evaluate the safety and efficacy of a Response Guided Therapy of boceprevir 800 mg dosed three times a day (TID) orally (PO) in combination with Peginterferon (either alpha 2b or alpha 2a) and Ribavirin in HIV/HCV genotype 1 infected patients that failed to previous HCV therapy.
Detailed description
In a total number of 108 patients the protocol was evaluated but only in 102 the protocol efectively was presented. In the remaining 6 patients we don't believe the trial could be performed.
Interventions
DRUGboceprevir
DRUGRibavirin
DRUGPeginterferon alfa-2a
DRUGPeginterferon alfa-2b
Sponsors
Anna Cruceta
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* For inclusion in the study, subjects must have a qualifying regimen defined as peginterferon alfa-2a plus ribavirin or peginterferon alfa-2b plus ribavirin for a minimum of 12 weeks. If a subject has received more than one such regimen, the most recent regimen is considered the qualifying regimen. * Subject must have previously documented chronic hepatitis C (CHC) genotype 1 infection. Subjects with other or mixed genotypes are not eligible. The HCV-RNA result at the screening visit must confirm genotype 1 infection and be ≥10,000 IU/mL. * Subject must have a liver biopsy with histology consistent with CHC and no other etiology and/or Fibroscan assessment. In case of: 1. No cirrhosis. Biopsies and/or Fibroscan must be within 18 months of screening visit. 2. Cirrhosis. No specific length of time would be requested. * All patients with cirrhosis must have an ultrasound 6 month within of screening visit. * Patients must be on stable antiretroviral therapy including a CD4 cell count of more than 100 per mm3 and a HIV plasmatic viral load undetectable (it is \< 50 copies/mL) for more than 6 months. Antiretroviral therapy must be Raltegravir-based (al least during the last 3 months). * Subject must be ≥18 years of age. * HIV treatment should not contain efavirenz (EFV), nevirapine (NVP), etravirine (ETV), didanosine (ddI), stavudine (d4T), zidovudine (AZT), or HIV protease inhibitors. * Subject must weight between 40 kg and 125 kg. * Subject and subject's partner(s) must each agree to use acceptable methods of contraception for at least 2 weeks prior to Day 1 and continue until at least 6 months after last dose of study drug. * Subjects must be willing to give written informed consent and by investigator opinion be able to follow the protocol visit design.
Exclusion criteria
* Subjects known to be coinfected with hepatitis B virus (HBsAg positive). * Patients chronically infected with HCV genotype other than 1 * CD4 cell count \< 100 cel/mm3. * Plasma HIV RNA more than 50 copies/mL * Platelet count less than 80.000 /mm3 * Subjects who required discontinuation of previous interferon or ribavirin regimen for a severe adverse event considered by the investigator to be possibly or probably related to ribavirin and/or interferon. * Treatment with ribavirin within 90 days and any interferon-alpha within 1 month of Screening. * Treatment for hepatitis C with any investigational medication. Prior treatments with herbal remedies with known hepatotoxicity are exclusionary. * Participation in any other clinical trial within 30 days of randomization or intention to participate in another clinical trial during participation in this study. * History of hemoglobinopathy (e.g., thalassemia) or any other cause of or tendency to hemolysis. * Evidence of decompensate liver disease including, but not limited to, a history or presence of clinical ascites, bleeding varices, or hepatic encephalopathy. * Diabetic and/or hypertensive subjects with clinically significant ocular examination findings. * Unstable or untreated pre-existing psychiatric condition. * Any known pre-existing medical condition that could interfere with the subject's participation in and completion of the study. * Any current evidence of substance abuse of alcohol or other drugs. * Subjects receiving opioid agonist substitution therapy but not enrolled in an opiate substitution maintenance program.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Sustained Virological Response (SVR) at 24 Weeks Post-Treatment | Week 24 | Achievement of SVR, defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. If a subject is missing FW 24 data and has undetectable HCV-RNA level at FW 12, the subject would be considered an SVR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of Sustained Virological Response at Weeks 2,4,8,12. | Weeks 2, 4, 8, 12 | Proportion of participants with undetectable HCV RNA (\<15 IU/mL) at weeks 2, 4, 8, and 12 during treatment. |
| The Proportion of Subjects With Undetectable HCV-RNA at FW 12. | Week 12 | The proportion of subjects with undetectable HCV-RNA at follow-up week 12. |
| The Proportion of Subjects With Undetectable HCV-RNA at 72 Weeks After Randomization. | Week 72 | The proportion of randomized subjects with undetectable HCV-RNA at 72 weeks after randomization. |
| Number of Adverse Events | From baseline to study completion (up to 72 weeks) | Safety: number of adverse events |
| Resistance of HCV After Boceprevir (BOC) Containing Regimen | whenever resistance occurs during the study (from week 12 until the date the resistance occurs, assessed up to 72 weeks) | Resistance of HCV after boceprevir containing regimen. Blood samples will be collected at baseline and after HCV virological failure and resistance analysis will be done at the end of the study in a single Center (Hospital Clínic-Barcelona). |
Countries
Spain
Participant flow
Recruitment details
Started 21/06/2013 and finished 04/12/2013
Participants by arm
| Arm | Count |
|---|---|
| Boceprevir Plus Peginterferon/Ribavirin to Retreat HCV Genotyp boceprevir 800 mg three times a day (v.o.) in combination with peginterferon (alfa-2b or alfa-2a) and ribavirin | 98 |
| Total | 98 |
Baseline characteristics
| Characteristic | Boceprevir Plus Peginterferon/Ribavirin to Retreat HCV Genotyp |
|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 15 |
| Region of Enrollment Spain | 98 participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 98 |
| serious Total, serious adverse events | 6 / 98 |
Outcome results
Primary
Achievement of Sustained Virological Response (SVR) at 24 Weeks Post-Treatment
Achievement of SVR, defined as undetectable plasma HCV-RNA at Follow-up Week (FW) 24. If a subject is missing FW 24 data and has undetectable HCV-RNA level at FW 12, the subject would be considered an SVR.
Time frame: Week 24
Population: All patients who received at least one dose of study medication were included in the efficacy analysis.~Patients with detectable HCV RNA at week 12 were discontinued per protocol-defined futility criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Boceprevir + Ribavirin + Peginterferon | Achievement of Sustained Virological Response (SVR) at 24 Weeks Post-Treatment | Number of participants achieving SVR | 66 Participants |
| Boceprevir + Ribavirin + Peginterferon | Achievement of Sustained Virological Response (SVR) at 24 Weeks Post-Treatment | Number of participants not achieving SVR | 32 Participants |
Secondary
Achievement of Sustained Virological Response at Weeks 2,4,8,12.
Proportion of participants with undetectable HCV RNA (\<15 IU/mL) at weeks 2, 4, 8, and 12 during treatment.
Time frame: Weeks 2, 4, 8, 12
Secondary
Number of Adverse Events
Safety: number of adverse events
Time frame: From baseline to study completion (up to 72 weeks)
Secondary
Resistance of HCV After Boceprevir (BOC) Containing Regimen
Resistance of HCV after boceprevir containing regimen. Blood samples will be collected at baseline and after HCV virological failure and resistance analysis will be done at the end of the study in a single Center (Hospital Clínic-Barcelona).
Time frame: whenever resistance occurs during the study (from week 12 until the date the resistance occurs, assessed up to 72 weeks)
Secondary
The Proportion of Subjects With Undetectable HCV-RNA at 72 Weeks After Randomization.
The proportion of randomized subjects with undetectable HCV-RNA at 72 weeks after randomization.
Time frame: Week 72
Secondary
The Proportion of Subjects With Undetectable HCV-RNA at FW 12.
The proportion of subjects with undetectable HCV-RNA at follow-up week 12.
Time frame: Week 12