Safety Study of Low Dose Interleukin 2 (IL-2) Plus PEG-IFN/RBV In Chronic Hepatitis C Virus Genotype I

NCT00277758 | Terminated Phase 1 DMC

• 2 other identifiers: 00-092U01AI048224
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a treatment study trial, in which we will assess the safety and tolerability of daily dose IL-2, as monotherapy for 12 weeks, followed by IL2 in combination with PEG-IFN and RBV for 48 weeks in the treatment of chronic Hepatitis C.

Conditions

Hepatitis C

Keywords

Interleukin-2

Outcome Measures

Primary Outcomes (1)

• Determination of the safety and tolerability of 12 weeks IL2 monotherapy followed by 48 weeks of IL2 combined with PEG-IFN/RBV

  60 weeks of therapy followed by 24 weeks off therapy

Secondary Outcomes (1)

• Determination of specific immunologic responses to HCV. Immunologic assessment will be performed as the sme time intervals as the assays for plasma virus.

  60 weeks of therapy followed by 24 weeks off therapy

Study Arms (2)

1

EXPERIMENTAL

Interventions: 12 weeks of interleukin-2 administration, followed by 48 weeks of interleukin-2 + Ribavirin + interferon-alpha therapy, followed by 24 weeks off therapy

Biological: Interleukin 2; Drug: Ribavirin; Biological: Pegylated Interferon Alpha; Biological: Inteleukin-2

2

ACTIVE COMPARATOR

48 weeks of therapy with Ribavirin + interferon-alpha, followed by 24 weeks off therapy

Drug: Ribavirin; Biological: Pegylated Interferon Alpha; Drug: Ribavirin + Pegylated interferon-alpha

Interventions

Interleukin 2 BIOLOGICAL

Interleukin-2 at 1.2 mU/M2 administered subcutaneously daily

Also known as: Proleukin

1

Ribavirin DRUG

Ribavirin @ 800 mg daily (\< 65 kg body weight), 1000 mg (65-85 kg), and 1200 mg (\> 85 kg)

Also known as: Rebetrol

1; 2

Pegylated Interferon Alpha BIOLOGICAL

Pegylated-Interferon-alpha 1.5 ug/kg weekly subcutaneously.

Also known as: PEG-Intron

1; 2

Inteleukin-2 BIOLOGICAL

Interleukin-2 administered as a daily subcutaneous injection at 1.2 mU/M2 BSA

Also known as: Ribavirin, Interferon-alpha

1

Ribavirin + Pegylated interferon-alpha DRUG

Pegylated interferon-alpha administered 1.5 ug/kg weekly. Ribivirin 800 mg daily for body weight \<65 kg, 1000 mg for body weight 65-85 kg, and 1200 mg for body weight \>85 kg.

Also known as: PEG-Intron, Rebetrol

2

Eligibility Criteria

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

You may qualify if:

• Men and women, age \>18 years to \< 65 years.
• Ability and willingness to sign an informed consent.
• Hepatitis C antibody positive status confirmed by the NYPH laboratory.
• Genotype 1 HCV confirmed by the NYPH laboratory using the DupliType assay as performed by Quest Diagnostics.
• Liver biopsy demonstrating chronic hepatitis but without cirrhosis within 2 years of enrollment.
• Prothrombin time \< 3 seconds longer than control.
• Platelet count ≥75,000 mm3
• Neutrophil count ≥ 1000/mm3
• Hemoglobin ≥12 g/dL for women and ≥13 g/dL for men
• Subject must agree not to participate in a conception process (defined as active attempt to become pregnant or to impregnate, donate sperm, in vitro fertilization etc.) while on study drugs and for 6 months following permanent discontinuation of study therapy.
• Women of reproductive potential (defined for this study as sexually mature women who have not been post-menopausal for at least 24 consecutive months, or have not undergone hysterectomy or oophorectomy) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 MIU/mL performed within 30 days prior to enrollment and again within 24 hours before initiating study therapy.
• All subjects must not participate in a conception process, and if participating in sexual activity that could lead to pregnancy, male subjects must take every precaution to avoid risk of pregnancy for their female partners, women subjects/male partners must use two reliable methods of contraception simultaneously, while receiving study therapy and for 6 months following permanent discontinuation of study therapy.
• NOTE A: Reliable forms of contraception are a combination of two of the following methods: 1) condoms (male or female) with or without a spermicidal agent. 2) diaphragm or cervical cap with spermicide, 3) IUD, or 4) hormonal-based contraception.
• NOTE B: An IUD is an adequate method of contraception but increases the risk of pelvic inflammatory disease.

You may not qualify if:

• Previous IFN-alpha, RBV or IL2 therapy
• Any active viral hepatitis other than hepatitis C virus infection, as defined by the presence of IgM antibody to Hepatitis A Virus (HAV) within 30 days of enrollment, or Hepatitis B Virus Surface Antigen (HBsAg) positivity, or positive plasma HBV DNA by PCR methodology when HB core antibody is the only serologic marker of HBV infection within 30 days of entry.
• ALT and AST \> 5x ULN, total bilirubin \> 1.5 x ULN
• Signs/symptoms of advanced liver disease.
• Uncontrolled infection, except hepatitis C
• HIV infection as determined by HIV ELISA \& Western blot assay, and confirmed by plasma HIV assay (PCR or bDNA)
• Cardiac condition that cannot be controlled by medication: Because of the risk of anemia associated with RBV use and the potential to induce cardiac ischemia, subjects with a positive cardiac stress test are ineligible. Therefore, subjects \> 40 years of age with ≥ 1 risk factor for ASHD (i.e., hyperlipidemia, hypertension, smoking history, family history) should have an EKG preformed. If the EKG is abnormal and consistent with ischemic heart disease, the subject should have a cardiac stress test to R/O ASHD.
• CNS or psychiatric illness uncontrolled by medication. In particular, psychiatric illness, especially depression. Subjects with a psychiatric illness, a previous suicide attempt or hospitalization for a psychiatric Dx Will be enrolled at the discretion of the investigator.
• Concurrent therapy with any immune-modulating agents, e.g,. interleukins, interferons, therapeutic vaccines, corticosteroids, immunosuppressive agents (azathioprine, 6-mercaptopurine, Cyclosporine-A, FK506, Rapamycin, antilymphocyte antibodies).
• Pregnant or nursing women (all women of child bearing age should be using effective contraception)
• History of malignancy with receipt of cancer therapy within 24 weeks.
• Any severe illness that would make the subject unsuitable for the study.
• Active asthma, or asthma uncontrolled by medication.
• Any immunologically mediated disease, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus erythematosis, ITP, autoimmune hemolytic anemia, eczema, psoriasis.
• Untreated thyroid disease.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Interleukin-2; aldesleukin; Ribavirin; peginterferon alfa-2b; Interferon-alpha

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Interferon Type I; Interferons

Study Officials

• Kendall A Smith, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 12, 2006
• First Posted: January 16, 2006
• Study Start: March 1, 2004
• Primary Completion: July 1, 2006
• Study Completion: August 1, 2006
• Last Updated: March 7, 2008

Record last verified: 2008-03

Locations

US (1)