Phase I-II study of live oral cholera vaccine 638 in healthy adult volunteers in Cuba.

• Register: RPCEC
• Last refreshed on: 29 April 2013
• Main ID: RPCEC00000053
• Date of registration: 19/09/2008
• Primary sponsor: Finlay Institute
• Public title: Phase I-II study of live oral cholera vaccine 638 in healthy adult volunteers in Cuba.
• Scientific title: Randomized, double-blind, controlled, phase I-II study to determine the safety, reactogenicity and immunogenicity of a single dose of 1-9 x 10E9 CFU of the live attenuated oral cholera lyophilized vaccine obtained from 638 Vibrio cholerae O1 El Tor Ogawa strain, administered by oral route in healthy adult volunteers from both sex.
• Date of first enrolment: 21/02/2005
• Target sample size: 48
• Recruitment status: Closed
• URL: http://registroclinico.sld.cu/trials/RPCEC00000053-En
• Study type: Interventional
• Study design: Randomization: Randomized Controlled Trial Blinding: Double Blind Placebo: Placebo Assignment: Parallel Purpose: Treatment

Countries of recruitment

Cuba

Contacts

• Name: Dra. Hilda García Sánchez
• Affiliation: Finlay Institute

• Name: Dr Rodrigo Valera Fernández
• Affiliation: Finlay Institute

Key inclusion & exclusion criteria

Inclusion criteria: 1-Healthy female or male aged 18 to 40 years 2-Free from obvious health problems as established by medical history, clinical examination, laboratory tests and psychometric tests before entering into the study. 3-Written informed consent obtained from the subjects. 4-To approve a written examination in order to ensure the volunteers understanding related to the study (trial) and others elemental knowledge about cholera.
Exclusion criteria: 1-Previous history of immunodeficiency. 2-Cardiovascular, respiratory, renal, hematological, hepatic, gastrointestinal, neurological, endocrine, and psychiatric diseases or reticuloendothelial system disorders detected during the clinical examination or by laboratory tests. 3-History of Allergy to tetracyclines. 4-Previous history of immunization with cholera vaccine or infection with cholera. 5-Administration of immunoglobulins and/or antibiotics within 30 days preceding the treatment. 6-Positive serological test for human HIV-1-2 virus antibody. 7-Positive serological test for human hepatitis B surface antigen, or hepatitis A and C antibodies. 8-Stool cultures positive for an enteric pathogen. 9-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. 10-Administration of a vaccine not foreseen by the study protocol during the period starting one month before the application of the study vaccine and ending one month after that application. 11-Acute disease at the time of enrollment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. 12-Do not approve a written examination in order to ensure the volunteers understanding related to the study (trial) and others elemental knowledge about cholera. 13-Pregnancy adverted by women or detected by mean of a rapid B-HCG pregnancy test on urine. Women during the proximity of the menstrual period at the very moment of the admission of the trial were discarded.

Age minimum: 18 years
Age maximum: 40 years
Gender: Both

Health Condition(s) or Problem(s) studied

Cholera disease

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: skimm milk, peptone and sorbitol. The 638 strain obtained at the CNIC does not have CT genes and others also present into the CTXphi phage, and it has the haemaglutinin protease gene (hap) inactivated, in which the endoglucanase 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). This trial was designed in two stages; stage 1 evaluated two antiacid as the vaccine dissolvents. In this stage participated 16 volunteers whom were feeding with the vaccine, 8 volunteers with the vaccine diluted into the antiacid A (1,33% sodium bicarbonate ), and the 8 remain volunteers with the vaccine diluted into the antiacid B (sodium bicarbonate, ascorbic acid, manitol, lactose, sodium saccharine, polivinilpirrolidone). In the stage 1 participated 8 volunteers from the placebo group whom were feeding with lyoprotectors diluted into the antiacids; 4 with the antiacid A and 4 with the antacid B. The stage 2 was conformed by 18 volunteers whom were fed with the vaccine dissolved into the antiacid B and 6 volunteers from the placebo group whom were fed with lyoprotectors diluted into the antiacid B.

Primary Outcome(s)

Primary objectives: 1-To assess safety of 1-9x10E9 CFU of a single dose of 638 V. chorelae O1 El Tor Ogawa, a lyophilized live attenuated oral cholera vaccine. 2-To assess reactogenicity during 5 days after application of vaccine or placebo. 3-To assess the vibriocidal antibody response against Ogawa serotype on days 14, 28, 42, at month 6 and one year after. Primary endpoints: Safety and Reactogenicity: 1-Incidence of any expected grade 3 adverse event within 5 days after vaccine and (or) placebo administration. 2-Incidence of any other expected adverse events taking place within 7 days after treatment. 3-Incidence, intensity and relationship to the vaccine and (or) placebo administration of any unexpected adverse even during the whole trial (30 days). 4-Incidence and relationship to the vaccine and (or) placebo administration of any serious adverse events during the whole trial (30 days). 5-Incidence of clinical lab tests with pathologic values 7 days after vaccine and (or) placebo administration. 6-Identification of attenuated 638 strain V. cholerae O1 El Tor Ogawa, excreted by volunteers 5 days before and 3 days after the antibiotic treatment. Immunogenicity: 1-The Geometrical Mean Titer (GMT) of vibriocidal antibodies: Estimation of the mean of vibriocidal antibody titers detected in serum samples on days 14, 28, 42, at month 6 and one year after treatment in comparison with the titers before vaccine and (or) placebo administration. 2-Assessment of seroconversion: Seroconversion defined as a fourfold increase of vibriocidal antibody titers on days 14, 28, 42, at month 6 and one year after treatment in comparison with the titers before vaccine and (or) placebo administration.

Secondary Outcome(s)

Secondary objective: To demonstrate vaccine plus antiacid proposed as a final formulation, is suitable as the vaccine mixed with 1.33% sodium bicarbonate. Secondary endpoints: 1-Incidence, intensity and relation to the placebo plus antiacid A administration of any unexpected adverse event during the first stage (30 days). 2-Incidence, intensity and relation to the placebo plus B antiacid administration of any unexpected adverse event during the first stage (30 days). 3-Statistic signification (“p value”) between immunogenicity results of volunteers who were fed with placebo mixed with antiacid A and immunogenicity results of volunteers fed with placebo mixed with antiacid B.

Secondary ID(s)

CHO0104

Source(s) of Monetary Support

Council of State of the Republic of Cuba

Secondary Sponsor(s)

Centro Nacional de Investigaciones Científicas (CNIC) (Cuban National Center for Scientific Research).