Phase Ib-IIb trial of the live oral cholera vaccine 638 in adult volunteers in Mozambique.

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:

Randomized, double-blind, placebo controlled phase Ib-IIb study to evaluate the immunogenicity, safety and reactogenicity of 10E8-10E9 CFU single dose of 638 V. cholerae O1 El Tor Ogawa, oral, live attenuated cholera lyophilized vaccine in presumed-healthy adult female and male volunteers in Mozambique.

Secondary indentifying numbers:

If/colera/02

Issuing authority of the secondary identifying numbers:

Finlay Institute

Source(s) of monetary or material support:

Council of State of the Republic of Cuba and Mozambique Ministry of Health.

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:

Others instances

Authorization date :

07/12/2005

Reference number:

1020/IMS-3/Gns/06

Principal investigator

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

First name:

Ricardo

Last name:

Thompson

Medical Specialty :

Scientific Director of the National Institute of Health at the Ministry of Health of Mozambique.

Affiliation:

Imap Matola - Instituto do Magistério Primário

Postal address:

R Imap 504 Bº Matola C-Matola

City:

Matola, Maputo

País:

Mozambique

Zip Code:

P.O. Box 264

Telephone:

+53-25821720951

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:

Mozambique

Clinical sites:

Industrial and Commercial School of Matola, Mozambique. Dr. Ricardo Thompson, MDV, Ph.D., Scientific Director of the National Institute of Health at the Ministry of Health of Mozambique.

Research ethics committees:

National Committee of Bioethics for Health, Maputo: December 7, 2005.

Recruitment status

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

Recruitment status:

Complete

Date of first enrollment:

31/07/2006

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:

Cholera disease

Health condition(s) code:

Cholera/ prevention & control

Healthy Volunteers

Vibrio Infections

Gram-Negative Bacterial Infections

Bacterial Infections

Waterborne Diseases

Environmental Illness

Intervention(s):

The Vaccine under study formulated at the Finlay Institute, is a lyophilized live oral vaccine, composed by the attenuated strain 638 V. cholerae from the serogroup O1, the biotype El Tor and the serotype Ogawa, as the pharmaceutical active ingredient and lyoprotectors: skimmed milk, peptone and sorbitol. The 638 strain obtained at the CNIC does not have CT genes and others also present into the CTXphi phage. It has the haemaglutinin protease gene (hap) inactivated, in which the endoglucanasa A (celA) of the Clostridium thermocellum is inserted. The vaccine is orally feeding in a single dose. The placebo group will be fed with lyoprotectors without the pharmaceutical active ingredient (the attenuated 638 strain).

Intervention code:

Cholera Vaccines

Vaccines, Attenuated

Vibrio cholerae O1

Administration, Oral

Placebos

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):

Primary objectives: 1-To assess safety of 10E8-10E9 CFU single dose of 638 V. chorelae O1 El Tor Ogawa, a lyophilized live attenuated vaccine. 2-To assess reactogenicity during 14 days after application of vaccine or placebo. 3-To assess the vibriocidal antibody response against Ogawa serotype on days 0, 14 and 21 after treatment. Primary endpoints: 1-Incidence and relationship to the vaccine and (or) placebo administration of any serious adverse event within 30 days after vaccination. 2-Incidence of any grade 3 adverse event within 14 days after vaccine and (or) placebo administration. 3-Incidence of any other expected adverse events taking place within 14 days after treatment. 4-Incidence, intensity and relationship to the vaccine and (or) placebo administration of unexpected adverse events within 30 days after vaccination. 5-Incidence of out of normality range values and with clinical significance of the clinical lab tests, 7 days after vaccine and (or) placebo administration. 6-The Geometrical Mean titers of vibriocidal antibodies before vaccination, and on days 14, and 21 after vaccination in both groups of study. 7-Seroconversion defined as a fourfold increase of the initial titer with respect to the days 14 and (or) 21 titers in both groups of study.

Key secondary outcomes:

Secondary objectives: 1-To identify and to quantify, the attenuated 638 strains V. cholerae O1 El Tor Ogawa, excreted by volunteers every each third day, during the next 30 days after immunization. 2-To assess the ribotype, the lack of ctxAB genes, the presence of the hap::celA allele and the expression of CelA and OmpU proteins in V. cholerae O1 biotype El Tor strains isolated from volunteers stools on days 3, 6, 9, 15 and 30 of the study. 3-To describe the quantitative variation of CD4 and CD8 lymphocytes subpopulations and HIV viremia in volunteers, after treatment. Secondary endpoints: 1-To describe by mean of a survival analysis the dynamic of excretion, defining the event of interest as the occurrence of the third consecutive stool cultures negative of the attenuated 638 V. cholerae O1 El Tor Ogawa strain. 2-To calculate percentage of volunteers who shed the attenuated 638 strain V. cholerae O1 El Tor Ogawa every each 3 days during the next 30 days after vaccine feeding or until the occurrence of 3 consecutive stool negative cultures for 638 strain in both groups of study. 3-Percentage of V. cholerae O1 El Tor strains isolated from stools of volunteers on days 3, 6, 9, 15 and 30, which match with the 638 vaccine strain in the ribotype, the lack of ctxAB genes, the presence of the hap::celA allele, the expression of CelA and the lack of the expression of the OmpU proteins. 4-The mean, range and standard deviation to describe the variation of CD4 and CD8 lymphocytes subpopulations and HIV viremia in positive HIV volunteers on days 7, 14 and 21 after vaccination, as well as to describe the variation of CD4 and CD8 lymphocytes subpopulations using non-parametric test.

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:

40 years

Inclusion criteria:

1-Presumed-healthy adult male and female volunteers, between 18 to 40 years of age. 2-Written informed consent obtained from the subjects.

Exclusion criteria:

1-Clinical manifestation of immunodeficiency. 2-Acute or chronic diseases adverted by volunteer during clinical examination or detected by mean of laboratory test, including bronchial asthma, cancer, neurological diseases, cardiovascular diseases and convulsions. 3-Previous history of immunization with cholera vaccines. 4-Previous cholera infections adverted by volunteers on the last 3 years. 5-History of acute diarrheas 30 days before the beginning of the trial, or chronic diarrheas. 6-Stool positive cultures for V. cholerae. 7-Optical density two times higher than the mean of optical densities of the 3 negative serum in each ELISA assay for IgG cholera antitoxin serum antibodies, in a 1:200 serum dilution, (O.D. serum sample 1:200 > 2 x mean of negatives controls). Otherwise the presence of vibriocidal antibodies titer = 1280 seven days before immunization. 8-Axilary temperature >= 37.5 °C at the very moment of vaccine/placebo administration. 9-Administration of antibiotics, antimalaric drugs, immunoglobulins or any blood products within 30 days preceding the treatment. 10-Subject under antiretroviral treatment. 11-Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs prior to the treatment. Inhaled and topical steroids are allowed. 12-Administration of a vaccine not foreseen by the study protocol 30 days before the treatment. 13-Do not approve a written examination in order to ensure the volunteers understanding related to the study and others elemental knowledge about cholera. 14-History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. 15-Pregnancy woman or breast-feeding. 16-Alcoholism.

Type of population:

Adults

Type of participant:

Healthy volunteers

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:

120

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:

Hilda

Middle Name:

Maria

Last Name:

Garcia Sanchez

Specialty:

Bachelor in Biochemistry

Affiliation:

Finlay Institute

Postal Address:

Casa F. Ave 27, No 19805, La Lisa.

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

72731218

Email :

hgarcia@finlay.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:

Rodrigo

Last Name:

Valera Fernández

Specialty:

II Specialist in Microbiology

Affiliation:

Finlay Institute

Postal Address:

Casa F. Ave 27, No 19805, La Lisa.

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

72731218

Email :

rvalera@finlay.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:

RPCEC00000051

Date of Registration in Primary Registry:

2008-09-12

Record Verification Date:

2008-07-29 20:00

Link to the spanish version:

Click here [4]