Peginterferon Alpha-2b And Ribavirin to Treat Hepatitis C in HIV-Infected Patients

NCT00018031 | Completed Phase 2 Results

• 2 other identifiers: 01019401-I-0194
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C; HIV Infections

Keywords

Liver Disease; Virologic Response; Immune Mechanisms; Cirrhosis; Eradication; HIV; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Participants With Viral Decline at Day 3 & 28 With Predictors of Post Treatment Response

  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

  Day 3 and Day 28

Study Arms (1)

1

EXPERIMENTAL

Weekly Injection of peginterferon alfa-2b and weight based ribavirin (1-1.2g/day) for 48 weeks

Drug: Peginterferon alfa-2b; Drug: Ribavirin

Interventions

Peginterferon alfa-2b DRUG

Weekly injections for 48 weeks of a dose of 1.5mcg/Kg per week subcutaneously

Also known as: PegIntron, PEG-Intron, PegIntron Redipen, Sylatron

1

Ribavirin DRUG

Weight based Ribavirin dosing 1-1.2grams/day in divided (twice daily) doses for a total duration of 48 weeks.

Also known as: ICN-1229, Copegus, Rebetol, Ribasphere, RBV, RTCA, Rebretron, Ribav, Ribavirine, Tribavirin, Vilona, Viramid, Virazid, Virazole, CAS Number: 36791-04-5

1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (14)

• Rozenberg L, Haagmans BL, Neumann AU, Chen G, McLaughlin M, Levy-Drummer RS, Masur H, Dewar RL, Ferenci P, Silva M, Viola MS, Polis MA, Kottilil S. Therapeutic response to peg-IFN-alpha-2b and ribavirin in HIV/HCV co-infected African-American and Caucasian patients as a function of HCV viral kinetics and interferon pharmacodynamics. AIDS. 2009 Nov 27;23(18):2439-50. doi: 10.1097/QAD.0b013e32832ff1c0.

  PMID: 19898214 RESULT

• Avidan NU, Goldstein D, Rozenberg L, McLaughlin M, Ferenci P, Masur H, Buti M, Fauci AS, Polis MA, Kottilil S. Hepatitis C viral kinetics during treatment with peg IFN-alpha-2b in HIV/HCV coinfected patients as a function of baseline CD4+ T-cell counts. J Acquir Immune Defic Syndr. 2009 Dec 1;52(4):452-8. doi: 10.1097/QAI.0b013e3181be7249.

  PMID: 19797971 RESULT

• Allison RD, Katsounas A, Koziol DE, Kleiner DE, Alter HJ, Lempicki RA, Wood B, Yang J, Fullmer B, Cortez KJ, Polis MA, Kottilil S. Association of interleukin-15-induced peripheral immune activation with hepatic stellate cell activation in persons coinfected with hepatitis C virus and HIV. J Infect Dis. 2009 Aug 15;200(4):619-23. doi: 10.1086/600107.

  PMID: 19594300 RESULT

• Nussenblatt V, McLaughlin M, Rehm CA, Lempicki RA, Brann T, Yang J, Proschan M, Highbarger HC, Dewar RL, Imamichi T, Koratich C, Neumann AU, Masur H, Polis MA, Kottilil S. Immunodeficiency and intrinsic IFN resistance are associated with viral breakthrough to HCV therapy in HIV-coinfected patients. AIDS Res Hum Retroviruses. 2007 Nov;23(11):1354-9. doi: 10.1089/aid.2007.0091.

  PMID: 18184077 RESULT

• Neumann A, Polis M, Rozenberg L, Jackson J, Reitano K, McLaughlin M, Koratich C, Dewar R, Masur H, Haagmans B, Kottilil S. Differential antiviral effect of PEG-interferon-alpha-2b on HIV and HCV in the treatment of HIV/HCV co-infected patients. AIDS. 2007 Sep 12;21(14):1855-65. doi: 10.1097/QAD.0b013e32825eaba7.

  PMID: 17721093 RESULT

• Wu L, Kottilil S, Lempicki R, Yang J, McLaughlin M, Hu Z, Koratich C, Reitano KN, Rehm CA, Masur H, Wood B, Kleiner DE, Polis MA. Hepatic histologic response (HR) to combination therapy among HCV/HIV-coinfected individuals: interferon induces HR independent of sustained virologic response (SVR). AIDS Res Hum Retroviruses. 2006 Nov;22(11):1091-8. doi: 10.1089/aid.2006.22.1091.

  PMID: 17147494 RESULT

• Pau AK, McLaughlin MM, Hu Z, Agyemang AF, Polis MA, Kottilil S. Predictors for hematopoietic growth factors use in HIV/HCV-coinfected patients treated with peginterferon alfa 2b and ribavirin. AIDS Patient Care STDS. 2006 Sep;20(9):612-9. doi: 10.1089/apc.2006.20.612.

  PMID: 16987047 RESULT

• Farel C, Suzman DL, McLaughlin M, Campbell C, Koratich C, Masur H, Metcalf JA, Robinson MR, Polis MA, Kottilil S. Serious ophthalmic pathology compromising vision in HCV/HIV co-infected patients treated with peginterferon alpha-2b and ribavirin. AIDS. 2004 Sep 3;18(13):1805-9. doi: 10.1097/00002030-200409030-00009.

  PMID: 15316341 RESULT

• Lempicki RA, Polis MA, Yang J, McLaughlin M, Koratich C, Huang DW, Fullmer B, Wu L, Rehm CA, Masur H, Lane HC, Sherman KE, Fauci AS, Kottilil S. Gene expression profiles in hepatitis C virus (HCV) and HIV coinfection: class prediction analyses before treatment predict the outcome of anti-HCV therapy among HIV-coinfected persons. J Infect Dis. 2006 Apr 15;193(8):1172-7. doi: 10.1086/501365. Epub 2006 Mar 13.

  PMID: 16544259 RESULT

• Sidique N, Kohli A, Shivakumar B, Migueles S, Subramanian GM, Naggie S, Polis MA, Masur H, Kottilil S. HIV/HCV-coinfected natural viral suppressors have better virologic responses to PEG-IFN and ribavirin than ARV-treated HIV/HCV patients. J Acquir Immune Defic Syndr. 2011 Oct 1;58(2):e38-40. doi: 10.1097/QAI.0b013e31822d463f. No abstract available.

  PMID: 21921725 RESULT

• Naggie S, Osinusi A, Katsounas A, Lempicki R, Herrmann E, Thompson AJ, Clark PJ, Patel K, Muir AJ, McHutchison JG, Schlaak JF, Trippler M, Shivakumar B, Masur H, Polis MA, Kottilil S. Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response. Hepatology. 2012 Aug;56(2):444-54. doi: 10.1002/hep.25647. Epub 2012 Jul 2.

  PMID: 22331604 RESULT

• Osinusi A, Naggie S, Poonia S, Trippler M, Hu Z, Funk E, Schlaak J, Fishbein D, Masur H, Polis M, Kottilil S. ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV. J Med Virol. 2012 Jul;84(7):1106-14. doi: 10.1002/jmv.23302.

  PMID: 22585729 RESULT

• Burbelo PD, Kovacs JA, Ching KH, Issa AT, Iadarola MJ, Murphy AA, Schlaak JF, Masur H, Polis MA, Kottilil S. Proteome-wide anti-hepatitis C virus (HCV) and anti-HIV antibody profiling for predicting and monitoring the response to HCV therapy in HIV-coinfected patients. J Infect Dis. 2010 Sep 15;202(6):894-8. doi: 10.1086/655780.

  PMID: 20684729 RESULT

• Chary A, Winters MA, Kottilil S, Murphy AA, Polis MA, Holodniy M. Impact of interferon-ribavirin treatment on hepatitis C virus (HCV) protease quasispecies diversity in HIV- and HCV-coinfected patients. J Infect Dis. 2010 Sep 15;202(6):889-93. doi: 10.1086/655784.

  PMID: 20677940 RESULT

MeSH Terms

Conditions

Hepatitis C; HIV Infections; Liver Diseases; Fibrosis

Interventions

peginterferon alfa-2b; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Digestive System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Shyam Kottilil
• Organization: NIAID/NIH

skottilil@niaid.nih.gov

301-435-036

Study Officials

• Shyam Kottilil, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Clinician

Study Record Dates

• First Submitted: June 27, 2001
• First Posted: June 28, 2001
• Study Start: June 1, 2001
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: October 1, 2014
• Results First Posted: October 1, 2014

Record last verified: 2014-09

Locations

US (1)