HEPCPR: Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients
Study Details
Study Description
Brief Summary
This study will evaluate the safety and effectiveness of combination therapy with peginterferon alfa-2b and ribavirin for treating hepatitis C virus (HCV) infection in HIV-infected patients. In studies of patients with hepatitis C alone, interferon alfa-2b plus ribavirin treatment eradicated the HCV in almost half the patients. Peginterferon alfa-2b is a compound that results from attaching a polyethylene glycol molecule to interferon alfa-2b. This compound stays in the blood longer than unmodified interferon alfa-2b, causing a higher blood concentration and thus maintaining activity against the hepatitis C virus.
HIV-infected patients 21 years of age and older with chronic hepatitis C infection and a viral load greater than 2000 copies/mL may be eligible for this 2 1/2-year study. Candidates will be screened with blood and urine tests and possibly a liver biopsy, if a recent one is not available. The liver biopsy is done to determine the severity of liver disease. For this test, patients are admitted to the NIH Clinical Center for 1 to 2 days. A sedative is injected into an arm vein, the skin in the area over the biopsy site is numbed with a local anesthetic, and a needle is inserted rapidly into and out of the liver to obtain a small tissue sample. The patient remains in the hospital overnight for monitoring. A chest X-ray, electrocardiogram (EKG) and liver ultrasound are also done. Within 4 weeks of the screening tests, candidates who appear eligible for the study will have a physical examination, medical history and repeat blood tests. Women who can become pregnant will have serial pregnancy tests throughout the study.
Patients who meet the study criteria and decide to participate will begin treatment with weekly injections under the skin of peginterferon alfa-2b and take ribavirin pills twice a day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Clinic visits will be scheduled as follows:
-
Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for safety tests and to measure blood levels of HIV and HCV.
-
Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 52, 56 and 64 - Blood and urine tests will be done to determine the side effects of treatment and its effect on the HCV infection.
-
Week 48 or end of treatment - Treatment will stop after 48 weeks. At this time, or earlier for those who do not complete the 48 weeks, patients will return to the clinic for a routine test.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
Hepatitis C infection occurs in one-third of all HIV-infected individuals. Liver disease has become more clinically significant among patients coinfected with HIV and HCV. Several studies have shown that coinfected individuals develop earlier and severe liver disease. Interferon with ribavirin has become the therapy of choice among people with non-genotype 1a. This is a pilot study to address the relationship of clinical response to combination therapy to the virologic and immunologic parameters. The study will also address the safety and efficacy of the peginterferon alfa-2b among HIV- infected individuals. The predictive ability of baseline HCV viral load, rate of decline of HCV viral load, HIV viral load and CD4 counts to the clinical response of chronic hepatitis to peginterferon and ribavirin will also be studied. Approximately sixty patients who are infected with both HIV and HCV and also have evidence of fibrosis will receive peginterferon alfa-2b and ribavirin for 48 weeks. In order to enroll sixty patients for this study, we will be screening a total of 180 patients. During the 72 weeks study these patients will be monitored for HCV viral load, and other HIV viral load and CD4 counts. Viral kinetics will also be monitored closely and the slope of second, slower phase decline of HCV viral load, which corresponds to the rate of infected cell death presumably may lead to sustained hepatitis C virologic response. The results of the study will enable us to better delineate the possible predictors of sustained response to peginterferon and ribavirin. The safety and tolerability of a combination therapy with peginterferon and ribavirin among HIV-infected individuals on antiretroviral therapy will further define the standard therapy of chronic hepatitis C in HIV-infected individuals.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Weekly Injection of peginterferon alfa-2b and weight based ribavirin (1-1.2g/day) for 48 weeks |
Drug: Peginterferon alfa-2b
Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously
Other Names:
Drug: Ribavirin
Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Participants With Viral Decline at Day 3 & 28 With Predictors of Post Treatment Response [Day 3 and Day 28]
HCV viral kinetics were used to predict rates of sustained virology response (SVR) in HIV/HCV connected subjects. Measure was determined by analyzing the population of participants with virologic decline of more than 1.0 log at day 3 combined with viral load of less than 5.0 log IU/ml at day 28 to predict sustained virology response
Eligibility Criteria
Criteria
- INCLUSION CRITERIA:
Age greater than or equal to 18 years.
Documentation of HIV-1 infection by any licensed ELISA test and confirmed by a Western Blot.
Documentation of Hepatitis C infection by demonstration of a positive test for hepatitis C antibody.
HCV RNA level greater than 2000 IU/ml by bDNA.
Infected with HCV genotype 1.
Histopathologic features consistent with chronic hepatitis C on liver biopsy at the time of enrollment.
Patients with CD4 greater than 300 cells/mm(3).
Ability to sign informed consent and willingness to comply with the study requirements and clinic policies.
Serum creatinine less than 1.5 mg/dL.
Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL).
Neutrophil count greater than or equal to 1000 cells/mm(3).
Platelets greater than or equal to 75,000/mm(3).
Hemoglobin greater than or equal to 8.0 mg/dL.
ALT less than 7 times the NIH upper limit of normal.
Serum lipase less than 1.5 times the NIH upper limit of normal.
Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to dosing with study medications.
If capable of pregnancy: use of effective contraception during study: effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception. This is advised on the basis of using ribavirin, which may have a potential teratogenic effect in pregnant women.
Need to have a primary doctor outside OP8 who will be taking care of the patients for their HIV infection and liver disease.
Willing to designate a person for durable power of attorney on the NIH form for medical research and medical care purposes at the NIH Clinical Center.
Ability to learn how to safely inject medication subcutaneously.
EXCLUSION CRITERIA:
PT-INR (in the absence of anti-cardiolipin antibody) prolonged by greater than 2 seconds.
Organ transplant recipient.
Elevated alpha-fetoprotein level (greater than 100 ng/mL).
Coexisting neoplastic disease requiring cytotoxic therapy.
Child Pugh's class B.
Severe cardiac or pulmonary decompensation.
Severe liver decompensation or advanced cirrhosis patients.
Severe psychiatric disorder that would interfere with the adherence to protocol requirements.
Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, and optic neuritis.
Preexisting uncontrolled seizure disorder.
Severe retinopathy.
Hemoglobinopathy
Direct bilirubin more than or equal to 2 times ULN.
No patients using long term systemic corticosteroids, immunosuppressives, or cytotoxic agents within 60 days of enrollment into the trial.
Chronic viral hepatitis of any other etiology other than hepatitis C.
Active systemic infections other than hepatitis C and HIV.
Liver disease caused by reasons other than hepatitis C like HBV, HDV, Wilson's hemochromatosis, autoimmune hepatitis (ANA greater than 160) except history of drug-associated hepatitis with discontinuation of the causative agent.
Hepatic mass suggestive of hepatocellular carcinoma.
Current alcohol or substance abuse that potentially could interfere with patient compliance.
Significant heart failure.
Evidence of esophageal varices.
Any systemic illness that will make it unlikely that the subject will be able to return to NIH for the required study visits.
Evidence of gastrointestinal malabsorption or chronic nausea or vomiting.
Male partners of pregnant women.
Currently taking didanosine (ddl or Videx-EC or Videx) as part of antiretroviral regimen.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
- Principal Investigator: Shyam Kottilil, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 010194
- 01-I-0194
Study Results
Participant Flow
| Recruitment Details | Patients were all recruited from other NIAID HIV clinical trials and from the nearby Maryland, Virginia and the District of Columbia HIV clinics |
|---|---|
| Pre-assignment Detail | Open label study. The participants were only excluded if they did not meet eligibility criteria, such as pregnancy, availability to make frequent clinic visits and able to meet laboratory safety criteria as described in the clinical protocol. |
| Arm/Group Title | Peginterferon Alfa-2b, Ribavirin |
|---|---|
| Arm/Group Description | Weekly Injection (Peginterferon alfa-2b) Peginterferon Alfa-2b : Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously Oral Pills (Ribavirin) Ribavirin : Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks. |
| Period Title: Overall Study | |
| STARTED | 36 |
| COMPLETED | 36 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Peg-interefron Alfa 2b, Ribavirin |
|---|---|
| Arm/Group Description | Weekly Injection Peginterferon alpha-2b : Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously Oral Pills Ribavirin : Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks. |
| Overall Participants | 36 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
34
94.4%
|
| >=65 years |
2
5.6%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
2
5.6%
|
| Male |
34
94.4%
|
| Region of Enrollment (participants) [Number] | |
| United States |
36
100%
|
Outcome Measures
| Title | Participants With Viral Decline at Day 3 & 28 With Predictors of Post Treatment Response |
|---|---|
| Description | HCV viral kinetics were used to predict rates of sustained virology response (SVR) in HIV/HCV connected subjects. Measure was determined by analyzing the population of participants with virologic decline of more than 1.0 log at day 3 combined with viral load of less than 5.0 log IU/ml at day 28 to predict sustained virology response |
| Time Frame | Day 3 and Day 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with Virologic decline at both Day 3 and absolute HCV VL at Week 28 were analyzed |
| Arm/Group Title | Peginterferon Alfa-2b, Ribavirin |
|---|---|
| Arm/Group Description | Weekly Injection (Peginterferon alfa-2b) Peginterferon Alfa-2b : Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously Oral Pills (Ribavirin) Ribavirin : Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks. |
| Measure Participants | 23 |
| Number [participants with post treatment svr] |
8
22.2%
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Peg-interefron Alfa 2b, Ribavirin | |
| Arm/Group Description | Weekly Injection Peginterferon alpha-2b : Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously Oral Pills Ribavirin : Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks. | |
All Cause Mortality |
||
| Peg-interefron Alfa 2b, Ribavirin | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Peg-interefron Alfa 2b, Ribavirin | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/36 (8.3%) | |
| Eye disorders | ||
| Vision Changes | 1/36 (2.8%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Carcinoma | 1/36 (2.8%) | 1 |
| Psychiatric disorders | ||
| Unusual affect or behavior | 1/36 (2.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Peg-interefron Alfa 2b, Ribavirin | ||
| Affected / at Risk (%) | # Events | |
| Total | 20/36 (55.6%) | |
| General disorders | ||
| Fatigue | 3/36 (8.3%) | 4 |
| Investigations | ||
| Anemia | 6/36 (16.7%) | 7 |
| Neutropenia | 15/36 (41.7%) | 43 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Shyam Kottilil |
|---|---|
| Organization | NIAID/NIH |
| Phone | 301-435-036 |
| skottilil@niaid.nih.gov |
- 010194
- 01-I-0194