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

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Evaluation of the vaccine candidate CIGB-230 in individuals with chronic renal insufficiency for the prevention of hepatitis C virus infection. Phase I/II clinical trial, controlled, randomized, blinded, adaptive.

Secondary indentifying numbers:

IG/VHI/HC/0801

Issuing authority of the secondary identifying numbers:

CIGB

Source(s) of monetary or material support:

Heber Biotec S.A.

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Center for State Control of the Quality of Drugs(CECMED)

Authorization date :

06/07/2009

Reference number:

767/05.017.09.B

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Jorge Pérez Oliva, MD

Last name:

Not entered

Affiliation:

Not entered

Postal address:

Not entered

City:

Not entered

Country:

Not entered

Zip Code:

Not entered

Email address:

email@not.entered [1]

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Havana City, “Calixto García” Hospital, Dr. Francisco Beltrán Havana City, “Miguel Enríquez” Hospital, Dr. Victor Remón Havana City, “Dr. Carlos J. Finlay” Military Hospital, Dr. Edgar Morejón

Research ethics committees:

Nefrology Institute, Havana City, December 9, 2008 "Calixto García" Hospital, April 1, 2009 "Miguel Enríquez" Hospital, Havana City, March 4, 2009 "Carlos J. Finlay" Military Hospital, Habana City, April 23, 2009

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Recruiting

Date of first enrollment:

29/10/2009

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

Infection with hepatitis C virus.

Intervention(s):

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.

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

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.

Key secondary outcomes:

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.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

18 years

Maximum age:

60 years

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.

Exclusion criteria:

Positive to anti-HCV. Positive to HCV RNA. Diagnosis of Lupus erithematosus or other documented collagen diseases Positive to HIV Positive to HBV Concomitant infection with HAV Women in fertile age that use hormone-based contraceptive methods. Women and men in reproductive age without contraceptive control. Pregnancy and breastfeeding. Body mass index under 16 Patients with previous diagnosis of sicklemia or hemophilia. Previous diagnosis of mental or psychiatric diseases. Patients with background of severe allergy (asthma degree III or IV). Consumption of immunosuppresive/ immunomodulators drugs at the inclusion or in the three months previous to the study. 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. Temporary exclusion criterium. Previous diagnosis of active cancer.

Type of population:

Adults

Type of participant:

Patients

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Prevention

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Placebo

Study design:

Parallel

Phase:

1-2

Target sample size:

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Zurina

Last Name:

Cinza Estevez

Affiliation:

Center for Genetic Engineering and Biotechnology.

Postal Address:

Ave 31, 158 and 190, Cubanacán, Playa

City:

Havana

Country:

Cuba

Zip Code:

6162

Telephone:

53-7- 2716022, ext 7227

Email :

zurina.cinza@cigb.edu.cu [2]

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Santiago

Last Name:

Dueñas-Carrera

Affiliation:

Center for Genetic Engineering and Biotechnology.

Postal Address:

Ave. 31 e/ 158 y 190 Cubanacán, Playa

City:

Havana

Country:

Cuba

Zip Code:

6162

Telephone:

53-7- 2716022, ext 7265

Email :

santiago.duenas@cigb.edu.cu [3]

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000098

Date of Registration in Primary Registry:

2010-09-27

Record Verification Date:

2010-09-08 20:00

Link to the spanish version:

Click here [4]