Hepatitis C InfectionNCT02112630
Boceprevir in End Stage Renal Disease (ESRD)
A study testing P-IFN alfa 2a, P-IFN alfa 2b and Ribavirin in people with Hepatitis C Infection and End Stage Renal Disease, run by Columbia University.
Trial summary
The purpose of the study is to assess the safety and efficacy of triple therapy with pegylated interferon (P-IFN), ribavirin and boceprevir in patients with genotype 1 chronic Hepatitis C Virus (HCV) infection and end stage renal disease (ESRD) on hemodialysis (HD). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatitis C Infection, End Stage Renal Disease
- What is being tested?
- P-IFN alfa 2a, P-IFN alfa 2b and Ribavirin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- May 2013to Feb 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (ages 18-75)
- Hepatitis C Virus ribonucleic acid (HCV RNA) 1000 IU/mL or greater
- Hepatitis C Virus (HCV) genotype 1
- End stage renal disease on hemodialysis
- Females of child bearing potential must be using an adequate method of contraception throughout the study and must have a negative pregnancy test prior to the start of treatment.
Who cannot join
- Intolerance to peg-IFN or ribavirin with prior treatment course.
- Prior treatment with protease inhibitor (telaprevir or boceprevir) or experimental protease inhibitor
- Significant cytopenias:
- Absolute neutrophil count (ANC) < 1000/mm3, OR
- Hemoglobin (Hgb) <10.5 g/dL, or
- Platelet count < 50,000/mm3
Show all 23Show fewer
- Significant laboratory abnormalities
- Direct bilirubin > 1.5 x upper limit of normal (ULN)
- Total bilirubin > 1.6 mg/dL unless due to Gilbert's disease
- Prothrombin time (PT)/Partial thromboplastin time (PTT) > 10% above laboratory reference range
- Thyroid Stimulating Hormone (TSH) > 1.2 x ULN or < 0.8 x lower limit of normal (LLN)
- Uncontrolled depression or psychiatric disease
- Uncontrolled cardiopulmonary or cardiovascular disease
- Autoimmune diseases except for treated thyroid disease
- Active substance abuse within 6 months of initiation of treatment
- Recent (within 4 weeks) episode of infection requiring systemic antibiotics
- Any medical condition that would be predicted to be exacerbated by therapy or that would limit study participation
- Any medical condition requiring or likely to require chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study
- Human immunodeficiency virus (HIV) or Hepatitis B Virus (HBV) co-infection
- Hepatocellular carcinoma (HCC) (Patients with HCC who are listed for liver transplantation may be included.)
- Other significant chronic liver disease diagnosis
- Evidence of decompensated liver disease
- Solid organ transplant recipient (Patients who have a history of renal transplant, and have experienced kidney graft loss, and are not on immunosuppression may be included.)
About this study
Official title: Prospective, Single-Center, Open Label, Pilot Study of Safety and Efficacy of Triple Anti-Viral Therapy With Pegylated Interferon, Ribavirin, and Boceprevir in Patients With Genotype 1 Chronic HCV With End Stage Renal Disease
The purpose of the study is to assess the safety and efficacy of triple therapy with pegylated interferon (P-IFN), ribavirin and boceprevir in patients with genotype 1 chronic Hepatitis C Virus (HCV) infection and end stage renal disease (ESRD) on hemodialysis (HD).
Read the detailed description
Hepatitis C (HCV) remains the most common chronic infection in the United States with about 3 million people chronically infected. The majority of these patients in the U.S. have genotype 1 HCV infection, which has been the most difficult genotype to treat with the traditional regimen of pegylated-interferon (P-IFN) and ribavirin, leading to sustained virologic response (SVR) in less than 50% of cases. HCV is also an established risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD) and unfortunately the treatment is even less successful in these patients mainly limited by increased medication toxicity.
In spring of 2011, the FDA approved two new direct acting antivirals (DAA) for the treatment of chronic genotype 1 HCV, boceprevir and telaprevir, to be used in combination with Peg-IFN and ribavirin. This 'triple therapy' approach has significantly increased the response rate (increased SVR rates to about 80% in those patients who had never been previously treated) representing a significant advance in the field. In addition, several response-guided therapy approaches were tested to determine if treatment duration could be shortened based upon the virologic response on treatment.
To date, there have been no studies evaluating the safety and efficacy of triple therapy in patients with ESRD. However, a single dose pharmacokinetic study of boceprevir in subjects with ESRD on hemodialysis demonstrated that the mean maximum concentration achieved by boceprevir (Cmax) and bioavailability (AUC) were comparable in patients with ESRD and in healthy subjects. Mean t½, median Tmax and mean apparent oral total clearance (CL/F) values were also similar in healthy subjects and patients with ESRD. Boceprevir exposure was also similar on dialysis and non-dialysis days. These data suggest that boceprevir does not need to be adjusted in patients with ESRD on dialysis, and that it is not removed by hemodialysis. To date, there are no studies of telaprevir in ESRD patients.
The investigators therefore aim to study the safety and efficacy of triple therapy using boceprevir in combination with P-IFN and ribavirin in patients with stage 5 CKD (defined as glomerular filtration rate (GFR) < 15 mL.min.1.73m2 on permanent hemodialysis for stage 5). In addition, given the significant toxicity of treatment in this particular patient population, the investigators aim to study the efficacy of response guided therapy in those patients who are eligible for response-guided therapy based on prior studies (treatment naïve patients, and well documented history of relapse with prior treatment with P-IFN and ribavirin).
- Conditions
- Hepatitis C Infection, End Stage Renal Disease
- Being tested
- P-IFN alfa 2a, P-IFN alfa 2b, Ribavirin, Boceprevir
- Keywords
- Hepatitis C Infection, HCV, genotype 1, End Stage Renal Disease, ESRD, Boceprevir, Pegylated Interferon, Ribavirin
- Medical subject headings
- Hepatitis C, Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P-IFN alfa 2aDrug
Also called Pegylated-interferon alfa 2a
P-IFN alfa 2b 0.75 mcg/kg/week
P-IFN alfa 2bDrug
Also called Pegylated-interferon alfa 2b
P-IFN alfa 2a 135 mcg/kg/week
RibavirinDrug
Also called Copegus®
200 mg PO once daily or 200 mg PO three times a week
BoceprevirDrug
Also called Victrelis
800 mg PO three times daily starting at week 4
| Study group | Role | What they receive |
|---|---|---|
| Group 1 - Response Guided Therapy | Experimental | Treatment naive and documented relapsers : Subjects who have never been previously treated with P-IFN +/- ribavirin therapy and those who have documented relapse after P-IFN +/- ribavirin therapy.
Subjects in group 1 will receive P-IFN alfa 2a or P-IFN alfa 2b and ribavirin for a 4 week lead-in followed by the addition of boceprevir. Based on the patient's HCV-RNA levels at Treatment Week (TW) 8, TW12 and TW24 treatment with be continued for a total duration of 28 to 48 weeks.Subjects will be followed through treatment and up to 24 weeks post treatment. Receives: Drug: P-IFN alfa 2a; Drug: P-IFN alfa 2b; Drug: Ribavirin; Drug: Boceprevir |
| Group 2 - Fixed Duration Therapy | Experimental | Partial/Null Responders /Undefined Previous Response, Compensated cirrhosis: Subjects who have compensated cirrhosis, and/or were previously treated with P-IFN +/- ribavirin without SVR (including partial responders, null responders, and those previously treated without adequate documentation of response).
Subjects in Group 2 will all be assigned to fixed duration therapy.Patients will be treated with P-IFN alfa 2a or P-IFN alfa 2b and ribavirin for a 4 week lead-in followed by the addition of boceprevir for a total of 48 weeks of therapy. Subjects will be followed through treatment and up to 24 weeks post treatment. Receives: Drug: P-IFN alfa 2a; Drug: P-IFN alfa 2b; Drug: Ribavirin; Drug: Boceprevir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who achieve sustained virologic response
Primary efficacy is the proportion of patients who achieve sustained virologic response at week 12 after discontinuation of all therapy (SVR12).
Measured: Up to 12 weeks after discontinuation of all therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2014 (estimated)
- Study startMay 2013
- Primary completionFeb 2015
- Study completionFeb 2015
Why it stopped: Poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis C InfectionStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Elizabeth C Verna, MD, MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02112630
- Sponsor's protocol ID
- AAAL5200
- Status last verified
- Sep 2015
- First submitted
- 2 Apr 2014
- Last updated
- 23 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective, Single-Center, Open Label, Pilot Study of Safety and Efficacy of Triple Anti-Viral Therapy With Pegylated Interferon, Ribavirin, and Boceprevir in Patients With Genotype 1 Chronic HCV With End Stage Renal Disease
- ClinicalTrials.gov ID
- NCT02112630
- Acronym / sponsor ID
- AAAL5200
- Conditions
- Hepatitis C Infection, End Stage Renal Disease
- Keywords
- Hepatitis C Infection, HCV, genotype 1, End Stage Renal Disease, ESRD, Boceprevir, Pegylated Interferon, Ribavirin
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Poor enrollment
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- May 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 14 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the safety and efficacy of triple therapy with pegylated interferon (P-IFN), ribavirin and boceprevir in patients with genotype 1 chronic Hepatitis C Virus (HCV) infection and end stage renal disease (ESRD) on hemodialysis (HD).
Detailed description
Hepatitis C (HCV) remains the most common chronic infection in the United States with about 3 million people chronically infected. The majority of these patients in the U.S. have genotype 1 HCV infection, which has been the most difficult genotype to treat with the traditional regimen of pegylated-interferon (P-IFN) and ribavirin, leading to sustained virologic response (SVR) in less than 50% of cases. HCV is also an established risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD) and unfortunately the treatment is even less successful in these patients mainly limited by increased medication toxicity.
In spring of 2011, the FDA approved two new direct acting antivirals (DAA) for the treatment of chronic genotype 1 HCV, boceprevir and telaprevir, to be used in combination with Peg-IFN and ribavirin. This 'triple therapy' approach has significantly increased the response rate (increased SVR rates to about 80% in those patients who had never been previously treated) representing a significant advance in the field. In addition, several response-guided therapy approaches were tested to determine if treatment duration could be shortened based upon the virologic response on treatment.
To date, there have been no studies evaluating the safety and efficacy of triple therapy in patients with ESRD. However, a single dose pharmacokinetic study of boceprevir in subjects with ESRD on hemodialysis demonstrated that the mean maximum concentration achieved by boceprevir (Cmax) and bioavailability (AUC) were comparable in patients with ESRD and in healthy subjects. Mean t½, median Tmax and mean apparent oral total clearance (CL/F) values were also similar in healthy subjects and patients with ESRD. Boceprevir exposure was also similar on dialysis and non-dialysis days. These data suggest that boceprevir does not need to be adjusted in patients with ESRD on dialysis, and that it is not removed by hemodialysis. To date, there are no studies of telaprevir in ESRD patients.
The investigators therefore aim to study the safety and efficacy of triple therapy using boceprevir in combination with P-IFN and ribavirin in patients with stage 5 CKD (defined as glomerular filtration rate (GFR) < 15 mL.min.1.73m2 on permanent hemodialysis for stage 5). In addition, given the significant toxicity of treatment in this particular patient population, the investigators aim to study the efficacy of response guided therapy in those patients who are eligible for response-guided therapy based on prior studies (treatment naïve patients, and well documented history of relapse with prior treatment with P-IFN and ribavirin).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 - Response Guided Therapy | Experimental | Drug: P-IFN alfa 2a, Drug: P-IFN alfa 2b, Drug: Ribavirin, Drug: BoceprevirTreatment naive and documented relapsers : Subjects who have never been previously treated with P-IFN +/- ribavirin therapy and those who have documented relapse after P-IFN +/- ribavirin therapy. Subjects in group 1 will receive P-IFN alfa 2a or P-IFN alfa 2b and ribavirin for a 4 week lead-in followed by the addition of boceprevir. Based on the patient's HCV-RNA levels at Treatment Week (TW) 8, TW12 and TW24 treatment with be continued for a total duration of 28 to 48 weeks.Subjects will be followed through treatment and up to 24 weeks post treatment. |
| Group 2 - Fixed Duration Therapy | Experimental | Drug: P-IFN alfa 2a, Drug: P-IFN alfa 2b, Drug: Ribavirin, Drug: BoceprevirPartial/Null Responders /Undefined Previous Response, Compensated cirrhosis: Subjects who have compensated cirrhosis, and/or were previously treated with P-IFN +/- ribavirin without SVR (including partial responders, null responders, and those previously treated without adequate documentation of response). Subjects in Group 2 will all be assigned to fixed duration therapy.Patients will be treated with P-IFN alfa 2a or P-IFN alfa 2b and ribavirin for a 4 week lead-in followed by the addition of boceprevir for a total of 48 weeks of therapy. Subjects will be followed through treatment and up to 24 weeks post treatment. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult (ages 18-75)
- Hepatitis C Virus ribonucleic acid (HCV RNA) 1000 IU/mL or greater
- Hepatitis C Virus (HCV) genotype 1
- End stage renal disease on hemodialysis
- Females of child bearing potential must be using an adequate method of contraception throughout the study and must have a negative pregnancy test prior to the start of treatment.
Key exclusion criteria (23 listed)
- Intolerance to peg-IFN or ribavirin with prior treatment course.
- Prior treatment with protease inhibitor (telaprevir or boceprevir) or experimental protease inhibitor
- Significant cytopenias:
- Significant laboratory abnormalities
- Uncontrolled depression or psychiatric disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| P-IFN alfa 2aAlso: Pegylated-interferon alfa 2aP-IFN alfa 2b 0.75 mcg/kg/week | Drug | Group 1 - Response Guided Therapy, Group 2 - Fixed Duration Therapy |
| P-IFN alfa 2bAlso: Pegylated-interferon alfa 2bP-IFN alfa 2a 135 mcg/kg/week | Drug | Group 1 - Response Guided Therapy, Group 2 - Fixed Duration Therapy |
| RibavirinAlso: Copegus®200 mg PO once daily or 200 mg PO three times a week | Drug | Group 1 - Response Guided Therapy, Group 2 - Fixed Duration Therapy |
| BoceprevirAlso: Victrelis800 mg PO three times daily starting at week 4 | Drug | Group 1 - Response Guided Therapy, Group 2 - Fixed Duration Therapy |
Primary outcome
Proportion of patients who achieve sustained virologic response
Time frame: Up to 12 weeks after discontinuation of all therapy
Primary efficacy is the proportion of patients who achieve sustained virologic response at week 12 after discontinuation of all therapy (SVR12).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth C Verna, MD, MS principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A study testing P-IFN alfa 2a, P-IFN alfa 2b and Ribavirin in people with Hepatitis C Infection and End Stage Renal Disease, run by Columbia University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 23 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who achieve sustained virologic response (time frame: Up to 12 weeks after discontinuation of all therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2015.