Phase I/II clinical trial for the evaluation of vaccine candidate CIGB-230 in patients with chronic renal insufficiency.

INTERVENTION: The study will involve four groups of treatment (A, B, C y D), 15 individuals in each one, with 8 administrations, four weeks interval, through intramuscular injection. One group will receive placebo. The other 3 groups will receive CIGB‐230, each one with a different dose: Group A: CIGB‐230, dose 0.25 mg Group B: CIGB‐230, dose 0.5 mg Group C: CIGB‐230, dose 0.75 mg Group D: Placebo The first immunization with CIGB‐230 starts in pre‐dialysis stage, stage IV, and 8 injections are administered, independently of starting the hemodialysis process if necessary before finishing the last immunization. Once started the hemodialysis treatment, if detected HCV RNA at any moment, the individual will receive the registered treatment, based on IFN, according the established protocol, and in those individuals still receiving doses of CIGB‐230 or placebo, the administration of the vaccine candidate will continue up to complete de planned immunizations. If the hemodialysis treatment starts at least 2 months after the last immunization with CIGB‐230 or placebo, a booster dose, before starting the hemodialysis, will be applied with CIGB‐230 or placebo, according to randomized list, keeping the blinded design. CONDITION: Infection with hepatitis C virus. PRIMARY OUTCOME: Safety, during the time of treatment and follow‐up, adverse events will be monitored by specialized physicians. Adverse events (AE). Time of measurement: every 28 days ‐ Ocurrence of AE in the individual (Yes/No). ‐ Description of AE (Name of the AE). ‐ Time of the AE (Difference in dates for starting and ending of AE). ‐ Intensity of the AE (Slight, Moderate, Severe) ‐ Seriousness of the AE (Serious, No serious). ‐ Result of the AE (improve, no improve, no change) ‐ Causality relation (1.Very Probable, 2.Probable, 3.Possible, 4.Improbable, 5.No related, 6.No measurable). Adverse events will be actively monitored in the place of immunization up to one hour after the application of each dose of CIGB‐230 (or placebo), or in a passive way in the follow‐up interviews through a model that will be filled‐up by patients. Adverse events will be evaluated every 28 days after each immunization with CIGB‐230, considering all medical events presented, being or not causally related with the administration of the vaccine candidate. The evaluation will include: asking, temperature measuring, inspection of the inoculation site, and general physical examination. SECONDARY OUTCOME: Secondary Outcome: Virological ‐ Detection of HCV RNA (presence/absence); it will be evaluated by RT‐PCR method previous to the treatment (t=0), 4 weeks after finishing the treatment of 8 immunizations (t=8), before starting the hemodialysis and monthly from this moment up to 6 months in hemodialysis. Secondary Outcome: Immunogenicity ‐ Specific immune response against HCV (yes/no); samples will be collected for evaluation, according the availability of materials and the results of viral load, of specific immunological parameters (neutralizing antibodies, lymphoproliferative response against core, E1, E2 and NS3, IFN‐gamma secretion), at months 0, 8 and before starting the hemodialysis and 6 months after starting the hemodialysis. INCLUSION CRITERIA: Adults of both genders Age between 18 and 60 years Chronic renal insufficiency (CRI) in stage IV (criteria for posterior hemodialysis treatment) with glomerular filtrate between 24 and 15. Informed consent signed.