NASVAC therapeutic vaccine study

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:

“Safety, Tolerance and preliminary Efficacy of nasal administration of NASVAC therapeutic vaccine candidate in chronic hepatitis B patients- A phase I, open, not controlled clinical trial”.

Secondary indentifying numbers:

IG/VH-IN/HB/0802

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

HeberBiotec 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 :

04/08/2009

Reference number:

05.012.09.B

Principal investigator

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

First name:

Guillermo Fernando Fernández Maqueira, MD

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

Clinical sites:

Not applicable

Research ethics committees:

“Abel Santamaría” General Hospital, August 28, 2008.

Recruitment status

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

Recruitment status:

Complete

Date of first enrollment:

28/01/2010

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 B

Intervention(s):

The NASVAC vaccine will be administered to a unique treatment group, by the nasal route using a nasal spray device (Valois), according to the dose 100µg HBsAg + HBcAg, final volume: 1mL, following a 10 dose schedule separated at 14 days intervals.

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):

Adverse events (Yes, No). Measuring time: 6 hours, 24 hours, 48 ??hours, 72 hours and 7 days after each dose of vaccine nasal. Severity of reported adverse events (mild, moderate, severe). Measuring time: 6 hours, 24 hours, 48 ??hours, 72 hours and 7 days after each dose of vaccine nasal.

Key secondary outcomes:

Quantitative PCR (quantification of viral load of hepatitis B virus in the blood). Measuring Time: Weeks 12, 24, 36 and 48 after the start of the immunization schedule. Anti-HBsAg antibodies (Positive, Negative). Measuring Time: Weeks 12, 24, 36 and 48 after the start of the immunization schedule. Anti-HBeAg (Positive, Negative). Measuring Time: Weeks 12, 24, 36 and 48 after the start of the immunization schedule. HBsAg (Positive, Negative). Measuring Time: Weeks 12, 24, 36 and 48 after the start of the immunization schedule. Presence of HBeAg (Positive, Negative). Measuring Time: Weeks 12, 24, 36 and 48 after the start of the immunization schedule. Proliferative cellular response capacity of IFN gamma secretion in cultured cells stimulated with HBsAg and HBcAg antigens (lymphocyte proliferation index). Measuring Time: Weeks 14, 28, 40 and 52 after the start of the immunization schedule. Determination of basic haematological and clinical chemistry (amount of ALT, AST, creatinine, bilirubin and alkaline phosphatase). Measuring time: Weeks 2, 4, 6, 8, 10, 12, 14, 16.1 8, 20, 22, 24, 28, 32, 36, 40, 44, 48 and 52 after the start of the immunization schedule.

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:

65 years

Inclusion criteria:

1) Adults from 18 to 65 years old, both sexes. 2) HBsAg seropositivity longer than six months. 3) Serum ALT levels over the upper normal limit detected (at least one time) during the six month period prior to study enrollment. 4) Previous treatment with alpha 2b interferon or with hepatitis specific antivirals that failed to control viral infection. Patients considered intolerant to standard treatment due to medical criteria or adverse reactions to this kind of therapy are also allowed to enter the study. 5) Six month washout period of the last treatment with interferon or other antivirals. 6) Inform Consent Act signed by the subject.

Exclusion criteria:

1) History of acute or chronic diseases of respiratory airways. 2) Seropositivity for markers of Hepatitis C virus infection (HCV). 3) Seropositivity for markers of Human Immunodeficiency Virus infection (HIV1, 2). 4) Women in reproductive age without a birth control method or using a hormonal contraceptive. 5) Pregnancy, puerperium or breastfeeding. 6) Uncontrolled chronic diseases (eg., high blood pressure, diabetes mellitus, renal failure, heart failure, malignant neoplasia, hyperthyroidism, autoimmune diseases, epilepsy, severe mental depression, etc). 7) Treatment with Interferon or any other HBV specific systemic antiviral agent (eg. Lamivudine) in the 6 month prior to study enrollment. 8) History of concomitant liver diseases of any aethiology, ie. Alcoholism, autoimmune hepatitis, toxic hepatitis, Wilson´s Disease, Haemochromatosis. 9) History of liver transplantation, cirrhosis, or primary liver hepatocacinoma (diagnosis made by clinic or ultrasonography). 10) ALT or AST values over 500 U/L detected at any moment during the study. 11) Fever higher than 37.8ºC during or 24 hours prior to nasal administration of the vaccine candidate or acute infectious disease suspected by clinical examination. 12) History of receiving another experimental product or hepatitis B vaccine in the six months prior to study enrollment. 13) Haemoglobin levels below 9g/L, platelet levels below 50x109 /L, Global leukocyte count > 12x109 cells/L or below 3 x109 cells/L. 14) Underlying immunosuppressive disease or immunosuppressive/immunostimulantory drugs intake (including steroids) in the six month prior to study entry. 15) History of severe allergy that need continued treatment with steroids (Grade III or IV Asthma, urtycaria, Dermatitis, Bronchitis, etc). 16) Obvious mental incapacity to give written consent or to allow follow up of the patient.

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:

Non-randomized controlled trial

Masking:

Open

Control group:

Uncontrolled

Study design:

Single group

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:

Aristides

Last Name:

Aguilar Betancourt

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 e/ 158 y 190, Cubanacán, Playa.

City:

Havana

País:

Cuba

Zip Code:

6162

Telephone:

(53-7)-2716022

Email :

aristides.aguilar@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:

Aristides

Last Name:

Aguilar Betancourt

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 e/ 158 y 190 Cubanacán, Playa.

City:

Havana

País:

Cuba

Zip Code:

6162

Telephone:

(53-7)-2716022

Email :

aristides.aguilar@cigb.edu.cu [2]

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:

RPCEC00000110

Date of Registration in Primary Registry:

2011-05-16

Record Verification Date:

2011-04-26 20:00

Link to the spanish version:

Click here [3]