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

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 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.

Secondary indentifying numbers:

IG/VHI/HC/0701

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 :

03/02/2008

Reference number:

No. 195/05.027.07.10

Principal investigator

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

First name:

Dr. Marlén Castellanos

Last name:

Not entered

Affiliation:

Not entered

Postal address:

Not entered

City:

Not entered

País:

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

Research ethics committees:

Ethics Committee from the Gastroenterology Institute, Approval date: November 29, 2007.

Recruitment status

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

Recruitment status:

Recruiting

Date of first enrollment:

06/11/2008

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:

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).

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):

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).

Key secondary outcomes:

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.

Selection criterias

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

Gender:

Male/Female

Minimum age:

20 years

Maximum age:

60 years

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.

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:

Treatment

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Active

Study design:

Factorial

Phase:

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

Middle Name:

Cinza

Last Name:

Estevez

Affiliation:

Department of Clinical Trials, Vaccine Division, Biomedical Research, CIGB.

Postal Address:

31st Ave. between 158 and 190, Cubanacan, Playa.

City:

Havana city

País:

Cuba

Zip Code:

PO Box 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

Middle Name:

Dueñas

Last Name:

Carrera

Affiliation:

Hepatitis C Department, Vaccine Division, Biomedical Research, Centro de Ingeniería Genética y Biotecnología.

Postal Address:

31st Ave. between 158 and 190, Cubanacan, Playa.

City:

Havana city

País:

Cuba

Zip Code:

PO Box 6162.

Telephone:

(53-7)- 2716022, ext 7227.

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:

RPCEC00000074

Date of Registration in Primary Registry:

2009-02-11

Record Verification Date:

2009-01-12 19:00

Link to the spanish version:

Click here [4]