Revisions for CV638 ability to protect against homologous Vibrio cholerae 3008 virulent strain | Registro Público Cubano de Ensayos Clínicos

--- 9 January 2017 - 3:22pm by FINLAY
+++ 9 January 2017 - 3:28pm by FINLAY
 Efficacy endpoints
-.	Sub-clinical cholera infection (positive culture of V. cholerae O1 (negative celA )). Measurement time: Daily up to 10 days after the second intervention.
+.     Clinical cholera disease (moderate, severe: with positive culture of V. cholerae O1 (negative celA)). Measurement time: Daily up to 10 days after the second intervention.
-.	Non formed stool (grades 3-5) per volunteer and group (number of depositions in 48 hours) Measurement time: Daily up to 10 days after the second intervention.
+.	Sub-clinical cholera infection (positive culture of V. cholerae O1 (negative celA )). Measurement time: Daily up to 10 days after the second intervention.
-.	Total weight of unformed stools (grades 3-5) (weight converted to volume, 1 g = 1 mL) (weight value converted to volume, 1 g = 1 mL) Measurement time: Daily up to 10 days after Second intervention.
+.	Non formed stool (grades 3-5) per volunteer and group (number of depositions in 48 hours) Measurement time: Daily up to 10 days after the second intervention.
-.	Faecal excretion of V. cholerae O1 virulent strain (binary variable: +/-) Measurement time: Daily up to 10 days after Second intervention.
+.	Total weight of unformed stools (grades 3-5) (weight converted to volume, 1 g = 1 mL) (weight value converted to volume, 1 g = 1 mL) Measurement time: Daily up to 10 days after Second intervention.
-.	Concentration of V. cholerae O1 (celA negative) in feces per day, volunteer and group (value of V. cholerae concentration in CFU) Measurement time: for 10 days after the second intervention.
+.	Faecal excretion of V. cholerae O1 virulent strain (binary variable: +/-) Measurement time: Daily up to 10 days after Second intervention.
+.	Concentration of V. cholerae O1 (celA negative) in feces per day, volunteer and group (value of V. cholerae concentration in CFU) Measurement time: for 10 days after the second intervention.
 Safety endpoints
 .	Frequency of meteorism, headache, nausea, abdominal cramps, malaise, vomiting and fever (Number of volunteers with symptoms in 24 hours) Measurement time: 14 days after the first intervention.
 .	Frequency of unsolicited adverse events (number of volunteer with symptoms per day). Measurement time: during the first 14 days after the first intervention.
 .	Intensity of meteorism, headache, nausea, abdominal cramps, malaise, vomiting and fever (Mild, moderate, severe).  Measurement time: during 14 days after the first intervention.
 .	Intensity of of unsolicited adverse events (Mild, moderate, severe). Measurement time: during 14 days after the first intervention.
 Immunogenicity endpoints
 .	Vibriocidal antibodies geometric mean titres against V. cholerae O1 Ogawa (titer value). Measurement time: before, and at 14 days after first intervention.
 .	Seroconversion (number of volunteers that increase 4 times serum vibriocidal antibody titers values against V. cholerae O1 Ogawa) Measurement time: before, and at 14 days after first intervention.
 Tolerability endpoints
 .	Severity of meteorism, headache, nausea, abdominal cramps, malaise, vomiting and fever. (Absence of severe symptoms). Measurement time: during the first 14 days after the first intervention.
 .	Severity of unsolicited adverse events (Absence of severe symptoms) Measurement time: during the first 14 days after the first intervention.
 Other endpoints
 .	Serum vibriocidal antibodies titers against V. cholerae O1 Ogawa (titer value). Measurement time: before, and at 21 days after the second intervention.
 .	Cholera IgG antitoxin antibody titers measured by ELISA (titer value by optic density (O.D.)). Measurement time: before and at 21 days after the second intervention.
 years
-. Woman or man from 18 to 65 years of age.
+. Woman or man from 18 to 45 years of age.
 . Voluntariness expressed through written informed consent signed by the volunteer.
 . Good physical and mental state established by medical criteria by means of anamnesis and physical examination, as well as by electrocardiogram and the following complementary ones: complete blood count with erythrocyte sedimentation, hemoglobin: glycemia, creatinine, urea, uric acid, TGO, TGP, GGT, Alkaline phosphatase, and urine (cituria), within the reference parameters which were not clinically significant, before starting the study.
-/12/29
+/01/09
-/12/29
+/01/09

CV638 ability to protect against homologous Vibrio cholerae 3008 virulent strain

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.

Acronym of Public Title:

PVSVCHO

Scientific title:

A randomized, double blind, phase III clinical trial, to evaluate the ability of the CV638 attenuated live vaccine candidate Vibrio cholerae 638 O1 El Tor Ogawa strain, to prevent clinical cholera disease caused by the challenge with the virulent strain Vibrio cholerae 3008 .

Acronym of Scientific Title:

PVSVCHO

Secondary indentifying numbers:

If/colera/05

Issuing authority of the secondary identifying numbers:

Finlay Institute of Vaccines (IFV)

Source(s) of monetary or material support:

Finlay Institute of Vaccines (IFV) National Fund for Science and Innovation (FONCI)

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)

Reference number:

In process

Principal investigator

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

First name:

Pedro

Last name:

Mas Bermejo

Medical Specialty :

Physician, Second degree specialist in Epidemiology

Affiliation:

Institute of Tropical Medicine Pedro Kouri (IPK)

Postal address:

Autopista Novia del Mediodia Km. 6½, La Lisa

City:

Havana

Country:

Cuba

Zip Code:

11400

Telephone:

+53-725531121

Email address:

pmas@ipk.sld.cu

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:

Institute of Tropical Medicine Pedro Kouri (IPK), December 6th, 2016

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

06/03/2017

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

Health condition(s) code:

Cholera

Vibrio Infections

Gram-Negative Bacterial Infections

Bacterial Infections

Waterborne Diseases

Environmental Illness

Intervention(s):

Each group will compound by 60 subjects Group 1 (experimental): First intervention: All subjects will receive a 50 ml oral dose of CV638 with a concentration of 5,00E+08-5,00E+09 CFU of the attenuated live V. cholerae O1 El Tor Ogawa strain 638. Second intervention: Fifteen (15) days after the first intervention, 20 subjects will receive 50 ml oral suspension containing one dose virulent strain 3008 V. cholerae O1 El Tor Ogawa, with a concentration of 1– 9,00E+06 CFU. Ninety (90) days after the first intervention other 20 subjects will receive 50 ml of an oral suspension containing one dose V. cholerae O1 El Tor Ogawa virulent strain 3008, with a concentration of 1 – 9,00E+06 CFU. The 20 subjects remaining will not receive the second intervention. Group 2 (control): First intervention: All subjects will receive a 50 ml oral dose of Placebo. Second intervention: Fifteen (15) days after the first intervention 20 subjects will receive 50 ml of an oral suspension containing one dose virulent strain 3008 V. cholerae O1 El Tor Ogawa, with a concentration of 1– 9,00E+06 CFU. Ninety (90) days after the first intervention other 20 subjects will receive 50 ml of an oral suspension containing one dose V. cholerae O1 El Tor Ogawa virulent strain 3008, with a concentration of 1 – 9,00E+06 CFU. The 20 subjects remaining will not receive the second intervention.

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):

Clinical cholera disease (mild, moderate, severe: with positive culture of V. cholerae O1 (negative celA)). Measurement time: Daily up to 10 days after the second intervention.

Key secondary outcomes:

Efficacy endpoints 1. Clinical cholera disease (moderate, severe: with positive culture of V. cholerae O1 (negative celA)). Measurement time: Daily up to 10 days after the second intervention. 2. Sub-clinical cholera infection (positive culture of V. cholerae O1 (negative celA )). Measurement time: Daily up to 10 days after the second intervention. 3. Non formed stool (grades 3-5) per volunteer and group (number of depositions in 48 hours) Measurement time: Daily up to 10 days after the second intervention. 4. Total weight of unformed stools (grades 3-5) (weight converted to volume, 1 g = 1 mL) (weight value converted to volume, 1 g = 1 mL) Measurement time: Daily up to 10 days after Second intervention. 5. Faecal excretion of V. cholerae O1 virulent strain (binary variable: +/-) Measurement time: Daily up to 10 days after Second intervention. 6. Concentration of V. cholerae O1 (celA negative) in feces per day, volunteer and group (value of V. cholerae concentration in CFU) Measurement time: for 10 days after the second intervention. Safety endpoints 7. Frequency of meteorism, headache, nausea, abdominal cramps, malaise, vomiting and fever (Number of volunteers with symptoms in 24 hours) Measurement time: 14 days after the first intervention. 8. Frequency of unsolicited adverse events (number of volunteer with symptoms per day). Measurement time: during the first 14 days after the first intervention. 9. Intensity of meteorism, headache, nausea, abdominal cramps, malaise, vomiting and fever (Mild, moderate, severe). Measurement time: during 14 days after the first intervention. 10. Intensity of of unsolicited adverse events (Mild, moderate, severe). Measurement time: during 14 days after the first intervention. Immunogenicity endpoints 11. Vibriocidal antibodies geometric mean titres against V. cholerae O1 Ogawa (titer value). Measurement time: before, and at 14 days after first intervention. 12. Seroconversion (number of volunteers that increase 4 times serum vibriocidal antibody titers values against V. cholerae O1 Ogawa) Measurement time: before, and at 14 days after first intervention. Tolerability endpoints 13. Severity of meteorism, headache, nausea, abdominal cramps, malaise, vomiting and fever. (Absence of severe symptoms). Measurement time: during the first 14 days after the first intervention. 14. Severity of unsolicited adverse events (Absence of severe symptoms) Measurement time: during the first 14 days after the first intervention. Other endpoints 15. Serum vibriocidal antibodies titers against V. cholerae O1 Ogawa (titer value). Measurement time: before, and at 21 days after the second intervention. 16. Cholera IgG antitoxin antibody titers measured by ELISA (titer value by optic density (O.D.)). Measurement time: before and at 21 days after the second intervention.

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:

45 years

Inclusion criteria:

1. Woman or man from 18 to 45 years of age. 2. Voluntariness expressed through written informed consent signed by the volunteer. 3. Good physical and mental state established by medical criteria by means of anamnesis and physical examination, as well as by electrocardiogram and the following complementary ones: complete blood count with erythrocyte sedimentation, hemoglobin: glycemia, creatinine, urea, uric acid, TGO, TGP, GGT, Alkaline phosphatase, and urine (cituria), within the reference parameters which were not clinically significant, before starting the study. 4. Women of childbearing age who meet the following criteria: A.Negative pregnancy rapid test in the previous checkup, before vaccination and before the challenge, B. Agree to practice sexual abstinence or use an approved effective method of birth control within 2 months after vaccination, C. Agree to continue these precautions during the study and up to 30 days after the challenge. 5. Man of childbearing age who agrees not to conceive a child within 30 days of vaccination. 6. Subject that agrees not to participate in another clinical trial during the period.

Exclusion criteria:

1. Volunteers with VC titers greater than or equal to 320, five days before administration of CV638 or Placebo. 2. Volunteers seropositive to cholera antitoxin IgG by ELISA 10 days before CV638 or Placebo administration. 3. Acute disease detected in the week prior to the administration of CV638, Placebo. 4. Axillary temperature ≥ 37.5 ° C immediately prior to administration of CV638 or Placebo. 5. Personal history of chronic illness, except compensated asthma and hypertension. 6. History of immunosuppressive therapy (systemic steroids, cytostatics, etc.) or immunostimulants (interferons, transfer factor, gammaglobulins, levamisole, etc.) in the previous 30 days, excluding topical steroids or by inhalation. 7. History of therapy with immunoglobulins or blood products during the 6 months prior to administration of CV638 or Placebo. 8. History of antibiotic therapy, current or during the 10 days prior to administration of CV638, or Placebo. 9. History of cholera in the last 3 years. 10. History of immunization with cholera vaccines prior to the first intervention. 11. History of allergic reactions to any of the components of research or antacids, as well as to milk or lactose intolerance. 12. History of allergic reactions to doxycycline, azithromycin and ciprofoxacin. 13. History of Guillain-Barre syndrome. 14. Gestation. 15. Breastfeeding. 16. Clinically abnormal electrocardiogram at the previous check-up, defined as pathological Q waves or significant changes in the ST-T waves; Criteria of left ventricular hypertrophy; And any non-sinus rhythm, excluding isolated contractions. 17. Significant clinical abnormality detected on physical examination, including but not limited to pathological murmur, lymphadenopathy, hepatosplenomegaly, or abdominal scar of doubtful origin.

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:

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:

Rodrigo

Middle Name:

Felipe

Last Name:

Valera Fernandez

Specialty:

Physician, Second degree specialist in Microbiology

Affiliation:

Clinical Investigational Design and Implementation Unit, Department of Clinical Research, Clinical Research and Impact Assessment (DIC & EI), Finlay Institute of Vaccines

Postal Address:

Ave. 21 No. 19810 e/ 198 y 200, Atabey, Playa,

City:

Havana

Country:

Cuba

Zip Code:

1600

Telephone:

+537-2718331

Email :

rvalera@finlay.edu.cu

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:

Rafael

Last Name:

Fando Calzada

Specialty:

Degree in Biochemistry, PhD in Biological Sciences

Affiliation:

Director of the Infectious Diseases Area and Director of Research, National Center for Scientific Research

Postal Address:

Ave 25 y 158 N0 15202. Cubanacan, Playa. PO 6414

City:

Havana

Country:

Cuba

Zip Code:

12100

Telephone:

+537-2086548

Email :

rafael.fando@cnic.sld.cu

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:

RPCEC00000228

Date of Registration in Primary Registry:

29/12/2016

Record Verification Date:

2017/01/09

Next update date:

2018/01/09

Link to the spanish version:

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CV638 ability to protect against homologous Vibrio cholerae 3008 virulent strain

About the RPCEC

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