Pilot Therapy Using Betaine in Combination With Peginterferon Alpha-2a Plus Ribavirin in Subjects With Genotype 1 Hepatitis C Who Have Not Achieved a Sustained Viral Response With a Prior Course of Pegylated Interferon and Ribavirin

0133-09-FB

This is a non-randomized, open-label study examining the safety and efficacy of betaine in addition to standard anti-viral therapy in genotype 1 hepatitis C non-responders or relapsers to previous pegylated interferon plus ribavirin. Betaine (20 gm/day) in 2 divided doses will be added to Peginterferon alpha 2a (180 mcg) plus weight-based Ribavirin (1000 or 1200 mg/day, for body weight \< or \> 75 kg, respectively, for 48 weeks. Patients must be diagnosed with chronic hepatitis C, genotype I, and have undergone therapy for hepatitis C with pegylated interferon plus ribavirin. Subjects will be followed for safety, tolerability, hepatitis C viral response and the effect on interferon gene signaling in peripheral blood mononuclear cells during therapy.

2009-05-01

2011-01-12

2011-01-12

Terminated

Early phase I

2

Inclusion Criteria: * Subject must be willing to give informed consent and be able to adhere to dose and visit schedules. * History of chronic hepatitis C, genotype 1, non-responders or relapsers as documented by genotype testing and HCV RNA levels at 12 weeks ( \< 2 log change) during therapy or at 3 - 12 months post therapy, respectively. * Adult subjects 18-70 years of age, of either gender * Liver biopsy within 3 years prior to the screening 1 visit with a pathology report confirming that the histological diagnosis is consistent with chronic hepatitis C. * Compensated liver disease with the following maximum hematologic, biochemical and serologic criteria at the Screening visit (WNL=within normal limits) Hemoglobin \> 12 g/dl for females and \>13 g/dl for males, WBC \> 3000/mm3, Platelets \> 80,000/mm3, Direct Bilirubin - WNL. Indirect bilirubin - WNL, Albumin - WNL, Serum Creatinine - WNL. * Fasting glucose should be 70 -140 mg/dl, results between 116-140 require a HbA1c \< 8.5% * TSH - WNL * Subjects with a history of mild depression may be considered for entry in to this study provided that a pretreatment assessment of the subject's affective status supports that the subject is clinically stable. * Subjects with a history of substance abuse must have abstained from using the substance for at least one year prior to the Screening visit. * Antinuclear antibodies (ANA) \< 1:320 * No radiologic evidence of a focal mass suggestive of hepatoma and/or ascites. Exclusion Criteria: * Pregnant or nursing subjects. Subjects who intend to become pregnant during the study period. Subjects with partners who intend to become pregnant during the study period. * Prior response to therapy and failure to achieve SVR which may have been due to treatment non-compliance, in the assessment of the investigator based upon subject's medical history. * Participation in any clinical trial of a HCV protease inhibitor of any duration. Subjects may have received other investigational agents for the treatment of HCV, as long as they have also received an adequate course of Peg-IFN/RBV \[i.e., the investigational agent could not have replaced either Peg-IFN (such as Albuferon) or RBV (viramidine)\]. * History of new hepatitis C exposure within the last 6 months * Current or intended use of G-CSF and/or GM-CSF during the stud period is prohibited. Current use of erythropoietin (EPO) is prohibited. * Suspected hypersensitivity to any interferon product or ribavirin * Participation in any other clinical trial within 30 days of Screening visit 1 * Treatment with any investigational drug within 30 days of Screening visit 1. * Any other cause for liver disease other than CHC, including but not limited to: hemachromatosis, Alpha-1 antitrypsin deficiency, Wilson's disease, Autoimmune hepatitis, Alcoholic liver disease, Non-alcoholic steatohepatitis (NASH), Drug-related liver disease * Known coagulopathies including hemophilia * Known hemoglobinopathies * Known G6PD deficiency * Known coinfection with HIV and/or HBV * Evidence of active or suspected malignancy or a history of malignancy within the last five years (with the exception of adequately treated basal cell carcinoma of the skin). * Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices or hepatic encephalopathy * Subjects with organ transplants other than cornea or hair transplant * Any Known preexisting medical condition, that could interfere with the subject's participation in and completion of the study including, but not limited to moderate to severe depression, or a history of severe psychiatric disorder, such as psychosis, suicidal ideation and/or suicidal attempt; Subjects with a past history or current use of lithium and/or antipsychotic drugs; CNS trauma or seizure disorder; Clinically significant ECG abnormalities and/or significant cardiovascular dysfunction within the past 2 years prior to Screening ; Poorly controlled diabetes mellitis; Chronic pulmonary disease (COPD); Immunologically mediated disease such as inflammatory bowel disease, rheumatoid arthritis, idiopathic thrombocytopenia purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis or symptomatic thyroid disorder; Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids: History of, or active clinical gout. * Substance abuse, such as alcohol (\>80 g/day), IV drugs and inhaled drugs. Subjects with a history of substance abuse must have abstained from the abuse substance for at least one year. Subjects with clinically significant retinal abnormalities * Any other condition which in the opinion of the investigator would make the subject unsuitable for enrollment, or could interfere with the subject participating in and completing the protocol * Subjects who are part of the staff personnel directly involved with the study * Subjects who are immediate family members of the investigational study staff

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2023-11-30