Phase II clinical trial for the evaluation of the therapeutic vaccine candidate Terap C.

• Register: RPCEC
• Last refreshed on: 29 April 2013
• Main ID: RPCEC00000074
• Date of registration: 11/02/2009
• Primary sponsor: Center for Genetic Engineering and Biothecnology (CIGB), in Havana.
• Public title: Phase II clinical trial for the evaluation of the therapeutic vaccine candidate Terap C.
• Scientific title: EVALUATION OF SAFETY AND PHARMACODINAMY OF TERAP C: A VACCINE PREPARATION FOR THERAPEUTIC USE IN THE TREATMENT OF CHRONIC HEPATITIS CAUSED BY HEPATITIS C VIRUS. PHASE II CLINICAL TRIAL, CONTROLLED, RANDOMIZED, BLINDED.
• Date of first enrolment: 06/11/2008
• Target sample size: 90
• Recruitment status: Active
• URL: http://registroclinico.sld.cu/trials/RPCEC00000074-En
• Study type: Interventional
• Study design: Randomization: Randomized Controlled Trial Blinding: Double Blind Placebo: Active Assignment: Factorial Purpose: Treatment

Countries of recruitment

Cuba

Contacts

• Name: Zurina Estevez
• Affiliation: Department of Clinical Trials, Vaccine Division, Biomedical Research, CIGB.

• Name: Santiago Carrera
• Affiliation: Hepatitis C Department, Vaccine Division, Biomedical Research, Centro de Ingeniería Genética y Biotecnología.

Key inclusion & exclusion criteria

Inclusion criteria: 1.Adults of both genders. 2.Age between 20 and 60 years. 3.Clinical history of chronic hepatitis caused by hepatitis C virus (confirmed by liver biopsy in the last 12 months before starting the clinical study, anti-HCV positive by UMELISA VHC, HCV RNA positive by UMELOSA VHC). 4.Patients naïve to antiviral treatment. 5.HCV RNA genotype 1b. 6.Informed consent signed.
Exclusion criteria: 1.Positive to HBV or HIV markers (HIV-1-2) of infection in serum. 2.Concomitant infection with HAV. 3.Patients with concomitant background liver disease like alcoholism, autoimmune hepatitis, toxic, Wilson´s disease, haemochromatosis, obesity. 4.Women in fertile age that use hormone-based contraceptive methods. 5.Women and men in reproductive age without contraceptive control. 6.Pregnancy and breastfeeding. 7.Chronic no-compensated disease (high blood pressure, diabetes mellitus, chronic renal insufficiency, heart insufficiency, thyroid alterations, epilepsy, cancer, severe mind depression, etc.). 8.Patients with previous diagnosis of blood alterations (leukemia, hemophilia, and others). 9.Liver histology indicating cirrhosis or hepatocellular carcinoma. 10.Clinical laboratory values indicating alterations not related to HCV. 11.Concomitant immunosuppresive disease, consumption of immunosuppresive/ immunomodulators drugs (steroids, colony stimulating factor, etc.) in the six months previous to the study. 12.Documented autoimmune disease (systemic erithematosus lupus, reumatoid arthritis, multiple sclerosis, diabetes mellitus type I, etc.). 13.Patients with background of alcoholism and/or drug addiction (in case that no consumption during the last year, considerations might be done for inclusion). 14.Patients with background heart disease. 15.Patients with abnormal renal function at the moment of recruitment. 16.Patients with background of mind-related disorders. 17.Patients with background of severe allergy (asthma degree III or IV, urticary, dermatitis, bronchitis, etc.). 18.Fever above >37.8°C, in the moment or 24 hours previous to the administration of the vaccine, or acute infectious disease not related to HCV infection suggested by clinical evaluation.

Age minimum: 20 years
Age maximum: 60 years
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic hepatitis C.

Intervention(s)

The study will incluye 5 groups of treatment. The first one will include 30 patients treated with IFN alpha 2b plus ribavirin and a monthly dose with placebo (saline) instead of Terap C during 12 months, the second group will include 15 individuals that will be treated with interferon alpha 2b plus ribavirin during 12 months and they will receive the vaccine candidate Terap C on months 1, 2, 3, 4, 5, 6 and placebo in the months 7, 8, 9, 10, 11 and 12, the third group will include 15 individuals that will be treated with interferon alpha 2b plus ribavirin during 12 months and they will receive the vaccine candidate Terap C on months 1, 2, 3, 4, 5, 6, 7, 8, 9 and placebo in the months 10, 11 and 12, the group 4 will also include 15 individuals that will be treated with interferon alpha 2b plus ribavirin during 12 months and they will receive the vaccine candidate Terap C on months 4, 5, 6, 7, 8, 9 and placebo in the months 1, 2, 3, 10, 11 and 12, the group 5 will include 15 patients that will be treated with interferon alpha 2b plus ribavirin during 12 months and they will receive the vaccine candidate Terap C on months 4, 5, 6, 7, 8, 9, 10, 11, 12 and placebo in the months 1, 2 and 3. In each injection of Terap C will be administered 0.5 mg of plasmid DNA (pIDKE2) encoding for the HCV structural proteins (Core, E1, E2), mixed at the moment of application with 0.05 mg of a recombinant HCV core protein variant (Co.120), in 0.5 mL final volume. The preparation will be administered by intramuscular injection in the left deltoid. The interferon alpha 2b (3 M.U.I. administered by subcutaneous injection three times per week (every second day) and ribavirin daily by pills ingestion (1,000 mg for body weight up to 75 Kg or 1,200 mg for body weight above 75 Kg).

Primary Outcome(s)

Sustained virological response (HCV RNA undetectable 6 months after treatment conclusion), moment of evaluation: 18 months after starting treatment. It is expected that the immunization with Terap C, concomitant with IFN alpha 2b +ribavirin, in HCV chronically infected individuals, naïve to treatment, increase in at least 20% the number of individuals with HCV RNA undetectable at 18 months after starting treatment, with respect to the control group (treatment with IFN alpha 2b +ribavirin alone).

Secondary Outcome(s)

Secondary Outcome: Improvement in liver histology, moment of evaluation, 18 months after starting the treatment with respect to pre-treatment status. It is expected that the immunization with Terap C, concomitant with IFN Alpha 2b+ribavirin, in HCV chronically infected individuals, naïve to treatment, increase in at least 20% the number of individuals with reduction in fibrosis at 18 months after starting treatment, with respect to the control group (treatment with IFN alpha 2b+ribavirin alone) Secondary Outcome: Biochemical response (ALT, AST, creatinine, serum bilirubin, alkaline phosphatase, gamma GT), moment of evaluation, every four weeks, up to week 72 after starting the treatment. It is expected that the immunization with Terap C, concomitant with IFN alpha 2b+ribavirin, in HCV chronically infected individuals, naïve to treatment, increase in at least 20% the number of individuals with normal biochemical values at 18 months after starting treatment, with respect to the control group (treatment with IFN alpha 2b+ribavirin alone) Secondary Outcome: Safety, all adverse events detected during the first hour after immunization, or in monthly interviews up to 18 months after starting the treatment, will be recorded by using a notebook to be filled by the patients after each dose with the vaccine candidate. No serious adverse events are expected. Moment of evaluation, monthly up to 18 months after starting the treatment.

Secondary ID(s)

IG/VHI/HC/0701

Source(s) of Monetary Support

Heber Biotec S.A.