An Open Label Non-Randomized Dose Escalating Trial to Assess Safety and Tolerability of Alb-Interferon Alfa 2b Every Two Weeks With Ribavirin Among HIV/HCV Coinfected Individuals

NCT00489385 | Completed Phase 1

• 2 other identifiers: 07000107-I-0001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine if Albumin-linked interferon (Albinterferon alfa-2b) every 2 weeks is safe and tolerated by patients infected by both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). This is a new medication developed for HCV. It may help the immune system fight infections, especially those caused by viruses. Albinterferon alfa-2b appears quite similar to other interferons, in side effects and action in controlling HCV. Patients ages 18 and older who are infected with HCV genotype 1, are HIV positive, are infected with HCV, and have evidence of HCV-induced liver disease; and who are not pregnant or breast feeding may be eligible for this study. Many visits to NIH over a 76-week period are required. There will be collection of blood and urine, pregnancy test, and tests of HCV in the blood. A liver biopsy is required before start of the study if patients have not had one within 1 year. Another is done at the end of 72 weeks. An eye exam is done before start of the study and repeated later. An optional procedure called automated pheresis is done at the study beginning. Researchers can study patients' immunity to control HCV. Blood is drawn through a needle in an arm vein and spun in a machine to separate the desired blood component. Remaining blood is returned to the patient. Patients will receive Albinterferon alfa-2b at a dose of 900 mcg every 2 weeks for 48 weeks, by injection under the skin. Ribavirin is given at 1,000 mg or 1,200 mg by mouth twice daily, depending on a patient's weight. Side effects of Albinterferon alfa-2b are fatigue, headache, joint and muscle pain, and sleeplessness. The major side effect of ribavirin is anemia. Visits ranging from week 3 to 44 will determine the safety of Albinterferon alfa-2b and ribavirin and to see effects on reducing the HCV viral load. For weeks 48, 52, 56, 64, 72, and 76, patients will return for a clinic visit and blood tests. At week 72, an abdominal ultrasound and liver biopsy are done. Week 76 includes discussion of biopsy results.

Conditions

HIV Infections; HCV

Keywords

Fibrosis; Viral Kinetics; Hepatotoxicity; Immunity; HIV Infection; Hepatitis C; HCV; Treatment Experienced; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of two doses of Albinterferon alpha 2b with ribavirin.

Secondary Outcomes (1)

• Histologic, virologic responses to Albinterferon alpha 2b and ribavirin

Interventions

Albinterferon DRUG

Ribavirin DRUG

Albuferon DRUG

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 licensed ELISA test and confirmed by a Western Blot.
• Documentation of hepatitis C infection by demonstration of a positive test for hepatitis C antibody and HCV RNA level of 2000 copies/mL or greater.
• Histopathologic features consistent with chronic hepatitis C at the time of enrollment. A liver biopsy done for a subject within 24 months prior to his or her participation may be used as the baseline biopsy.
• Patients infected with genotype 1.
• Patients with CD4+ cell counts greater than 100 cells/mm(3).
• Ability to sign the Informed Consent document, and willingness to comply with the study requirements and clinic policies.
• Neutrophil count greater than 1000 cells/mm(3).
• Platelets greater than 75,000/mm(3).
• Hemoglobin greater than 10.5 g/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.
• If the patient is able to become pregnant, then she must use two effective methods of contraception during the study. Effective contraceptive 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 on the fetus in pregnant women.
• Willingness to not become pregnant until 7 months after completion of ribavirin therapy.

You may not qualify if:

• Patient cannot be on other experimental therapies (including expanded access/compassionate use of antiretrovirals) during his/her participation in this protocol.
• Patients cannot have used interferon or peginterferon previously for the treatment of hepatitis C.
• Mixed genotypes (e.g., 1/2, 1/4). Mixed genotype 1a/1b will be enrolled.
• Liver histology which, in the opinion of Clinical Center pathologist, is consistent with any other co-existent cause of chronic liver disease as defined as: chronic hepatitis B with positive HBsAg autoimmune hepatitis with a positive ANA greater than 1 unit or positive anti mitochondrial antibody greater than 1 unit; cholestatic disease with persistent elevation of alkaline phosphatase; primary biliary cirrhosis or sclerosing cholangitis; Wilson's disease; alpha-1-antitrypsin deficiency; steatohepatitis (alcoholic or non alcoholic) with marked steatosis, many Mallory bodies, or extensive zone 3 periportal fibrosis.
• Hemochromatosis or secondary iron overload as defined by (1) an elevated serum ferritin or an iron saturation (serum iron/IBC times 100%) of greater than 50%, and (2) presence of 3+ or more stainable iron on liver biopsy according to the study pathologist. Those subjects with, or a history of previous phlebotomy for iron overload will undergo HFE genetic counseling and those with a positive HFE genetic test demonstrating homozygosity for C282Y and H63D are not eligible. Those who have compound heterozygosity to C282Y and H63D are also not eligible.
• For patients with cirrhosis, a Child Turcotte Pugh score greater than 7.
• PT-INR greater than 2 or history of hemophilia or known history of Vitamin K deficiency or use of anticoagulants.
• Organ transplant recipient other than cornea or hair transplant.
• Estimated Creatinine clearance (eGFR) less than 50 mL/min.
• A serum alpha-fetoprotein level (greater than 20 ng/mL, unless the subject has a negative ultrasound before enrollment.
• For patients with history of diabetes mellitus, a HbA1C less than or equal to 7.5% and for those with a fasting blood glucose level of greater than 140mg/dL, a HbA1C of less than or equal to 7.5%.
• Coexisting neoplastic disease except for Kaposi's sarcoma, any non-metastatic skin cancer that has been resected, or non-metastatic cervical or anal cancer that has been resected.
• Severe cardiac disease (Grade 3 or more congestive cardiac failure, symptomatic coronary artery disease, significant arrhythmias, uncontrolled hypertension).
• Severe chronic pulmonary disease with functional impairment or a DLCO less than or equal to 50% at baseline.
• Severe psychiatric disorder that would interfere with the adherence to protocol requirements.

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 (3)

• Alter MJ, Mast EE. The epidemiology of viral hepatitis in the United States. Gastroenterol Clin North Am. 1994 Sep;23(3):437-55.

  PMID: 7989088 BACKGROUND

• Seeff LB, Buskell-Bales Z, Wright EC, Durako SJ, Alter HJ, Iber FL, Hollinger FB, Gitnick G, Knodell RG, Perrillo RP, et al. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med. 1992 Dec 31;327(27):1906-11. doi: 10.1056/NEJM199212313272703.

  PMID: 1454085 BACKGROUND

• Koretz RL, Abbey H, Coleman E, Gitnick G. Non-A, non-B post-transfusion hepatitis. Looking back in the second decade. Ann Intern Med. 1993 Jul 15;119(2):110-5. doi: 10.7326/0003-4819-119-2-199307150-00003.

  PMID: 8512159 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Fibrosis; Hepatitis C

Interventions

albinterferon alfa-2b; Ribavirin; albuferon

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 21, 2007
• Study Start: June 18, 2007
• Primary Completion: March 15, 2011
• Study Completion: March 15, 2011
• Last Updated: July 2, 2017

Record last verified: 2012-01-25

Locations

US (1)