Randomized double blind controlled, phase I clinical trial, to assess safety, reactogenicity and immunogenicity of the 638 vaccine candidate, in healthy female and male children and adolescents aged from 5 to 17 years old from Cienfuegos Province, Cuba.

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:

Secondary indentifying numbers:

If/cólera/03

Issuing authority of the secondary identifying numbers:

Finlay Institute, Center for Research and Production of Sera and Vaccines

Source(s) of monetary or material support:

Center for Research and Production of Sera and Vaccines (Finlay Institute) National Center for Scientific Research (CNIC) Ministry of Public Health (MINSAP)

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 Drugs, Medical Devices and Equipment (CECMED)

Authorization date :

10/09/2013

Reference number:

05.011.13B.A

Principal investigator

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

First name:

Jorge

Midle name:

Ernesto

Last name:

Perez Lastre

Medical Specialty :

Doctor in General Medicine, Specialized in First Degree Pediatric, Master in Infectology and Tropical Diseases

Affiliation:

"Pedro Kouri" Institute

Postal address:

Autopista Novia del Mediodía Km 6½, La Lisa.

City:

Havana

País:

Cuba

Zip Code:

P.O Box 601

Telephone:

+53-72553187

+53-72553226

Email address:

jorgee@ipk.sld.cu [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:

Centro Especializado Ambulatorio (CEA) “Héroes de Playa Girón”,Hospital Pediátrico Universitário “Paquito González Cueto"

Research ethics committees:

Finlay Institute, 14 de marzo de 2013

IPK, 1 de julio de 2013

"Dr. Gustavo Lima Aldereguía" Hospital, 28 de marzo de 2013

"Paquito Gonzalez Cueto" Pediatric University Hospital, 27 de marzo de 2013

Recruitment status

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

Recruitment status:

Complete

Date of first enrollment:

19/10/2013

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 infection

Intervention(s):

Study Group: Name of the intervention: Vaccinal candidate 638, Dose to be used: single dose (5,00E+08-5,00E+09 UFC), Administration route: oral. Control Group: Name of the intervention: Placebo, Dose to be applied: single dose, administration route: oral. The subjects will be hospitalized for 11 days in the isolation ward of the Clinical trial site, CEA. After the administration of the investigational products, in order to shorten the excretion period of the attenauate live strain 638, Azytromicin 20 mg/Kg of weight in single dose will be administered orally from the 5th day on. Hospital discharge will be evaluated according to clinical and epidemiological criteria, the study will be continued in outpatient form up to 14 days when it is concluded.

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 1.Serious adverse event (description of the event and relationship causality). Measurement time : during the 14 days after of the Investigational Products feeding. 2.Laboratory tests (out of range values of the results of the clinical laboratory tests of hematology and hemochemistry). Measurement time: 5 days after of the Investigational Products feeding. Reactogenicity 1.Degree 3 expected adverse events (frequency, onset and duration of the event). Measurement time: during 5 days after of the Investigational Products feeding. 2.Expected adverse event of any other intensity (frequency, onset and duration ). Measurement time: during 5 days after of the Investigational Products feeding. 3.Unexpected adverse event (frequency, onset, duration, intensity and relationship causality with the administration of the IP). Measurement time: during the 14 days of the Investigational Products feeding. Inmunogenicity 1.Vibriocidal antibody titers in serum against serotype Ogawa of V. cholerae. Measurement time: befote the administration of the IP, 5 and 14 days after of the Investigational Products feeding. 2.Seroconversion (increase of at least 4 times the titer of vibriocidal antibodies of V. cholerae against Ogawa serotype). Measurement time: during 5 and 14 days of the Investigational Products feeding.

Key secondary outcomes:

Acceptability of IP 1.Difficulty when taking of the Investigational Products, related to the organoleptic characteristics of the product. Measurement time: immediately after of the Investigational Products feeding. 2.Volume of the Investigational Products taken by volunteers. Measurement time: immediately after being fed. Reactogenicity and volume (greater than or equal to 50% or less than 50%) of taken IP Adverse events (frequency , onser and duration of the event). Measurement time: during the 5 days after of the Investigational Products feeding. Inmunogenicity according to volume (greater than or equal to 50% or less than 50%) of taken IP 1.Vibriocidal antibody titers inserum against serotype Ogawa from V. cholerae. Measurement time: before the administration of IP, 5 and 14 days of the Investigational Products feeding. 2.Seroconversion (increase of at least 4 times the vibriocidal antibody titers of V. cholerae against serotype Ogawa). Measurement time: 5 and 14 days of the Investigational Products feeding: Excretion of V. cholerae strains 1.Excretion of strains of V. cholerae 638 in heces samples of volunteers in both study groups, (by isolation, identification or CFU counting). Measurement time: Between the 3rd and 5th day of the Investigational Products feeding (before the administration of antibiotics). 2.Concentration in CFU of strain 638 quantified in volunteers' feces. Measurement time: Between the 3rd and 5th day of the Investigational Products feeding (before the administration of antibiotics). 3.Excretion of other strains of V. cholerae O1 in simples of volunteers' feces of both study groups (by isolation, identification or CFU counting). Measurement time: Between the 3rd and 5th day of the Investigational Products feeding (before the administration of antibiotics). 4.Concentration of strain 638 excreted by volunteers, according to the volume of IP taken in both groups. Measurement time: Between the 3rd and 5th day of the Investigational Products feeding (before the administration of antibiotics). 5. Genotypic characterizations of ribotypes, toxigenicity ctxAB, union hap::celA and phenotype accordting to detection of outer membrana proteins OmpT and OmpU and endoglucanase activity CelA in colonies. Measurement time: Between the 3rd and 5th day after of the Investigational Products feeding (before the administration of antibiotics).

Selection criterias

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

Gender:

Male/Female

Minimum age:

5 years

Maximum age:

17 years

Inclusion criteria:

1. Female and male adolescents and children aged from 5 to 17 years old, located between the 10th and 90th percentile, according to the Cuban population nutritional evaluation tables. 2. Good physical and mental health criteria established by anamnesia, physical examination, and results of the hematology, hemochemistry and urine laboratory tests within reference parameters, before the beginning of the study. 3. Expressed willfulness by means of a written Informed Consent, signed either by the father, the mother or the legal tutor of the girls and boys, and by the approval of the children of 10 or more years old..

Exclusion criteria:

The participant should not be included if complies with at least one of the following criteria: 1. Transmissible or non-transmissible chronic disease referenced or detected during a clinical examination. 2. Acute illness detected in the previous week when the investigational product be fed, with or without fever. 3. Anemia with hemoglobin levels below 10 g / dl, according to the WHO criteria. 4. Axiliary temperature ≥ 37.5°C immediately previous to the Investigational products be fed. 5. Congenital or acquired immunodeficiency. 6. To be under immunosuppressive therapy (more than 14 days before administration of the Investigational Products) or other medication that modifies the immune status, excluding topical or inhaled steroids. 7. History of therapy with immunoglobulin or blood products within 6 months prior to the administration of the vaccine candidate or placebo. 8. History of antibiotic therapy during the 28 days prior to the administration of the Investigational Products or benzathine penicillin therapy. 9. Allergy to medications under study. 10. Change in the normal stool pattern of the volunteers in the month previous to the study. 11. History of acute diarrhea event 30 days before the clinical trial starts or history of chronic diarrhea events. 12. At least one episode of abdominal pain for more than 2 weeks in the last 30 days and (or) anorexia, nausea, malaise or vomiting in the last 24 hours. 13. Antecedent of cholera disease in the last three years. 14. Previous history of immunization with vaccines against cholera. 15. V. cholerae O1 Positive stool culture. 16. Volunteers with vibriocidal antibody titer more than 20, seven days before the investigational products feeding. 17. Volunteers with IgG antibody titers by ELISA cholera antitoxin, seven days previous to the investigational products feeding. 18. History of allergic reactions to any component of the vaccine candidate, placebo or antacid as well as milk intolerance. 19. Positive pregnancy test in menstruant girls .

Type of population:

Children

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:

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:

Hilda

Middle Name:

Maria

Last Name:

Garcia Sanchez

Specialty:

Biochemist, Master of Science in Bacteriology and Mycology, Doctor of Health Sciences

Affiliation:

Clinical Trial Department, Commercial Vice-presidency. Finlay Institute

Postal Address:

Ave. 27 No. 19805, La Coronela, La Lisa.

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

(537) 208 6086; 208 0986

Email :

hgarcia@finlay.edu.cu [2]

hildamaria@infomed.sld.cu [3]

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:

Hilda

Middle Name:

Maria

Last Name:

Garcia Sanchez

Specialty:

Biochemist, Master of Science in Bacteriology and Mycology, Doctor of Health Sciences

Affiliation:

Clinical Trial Department, Commercial Vice-presidency. Finlay Institute

Postal Address:

Ave 27, No.19805, The Lisa,

City:

Havana

País:

Cuba

Zip Code:

11600

Telephone:

(537) 208 6086; 208 0986

Email :

hgarcia@finlay.edu.cu [2]

hildamaria@infomed.sld.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:

RPCEC00000172

Date of Registration in Primary Registry:

11/10/2013

Record Verification Date:

2014/09/22

Next update date:

2015/09/22

Link to the spanish version:

Click here [4]