HeberNasvac® Phase IV in Chronic Hepatitis B

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:

Post-licensing study of the therapeutic vaccine HeberNasvac® in patients with chronic hepatitis B virus infection

Secondary indentifying numbers:

IG/VTIN/HB/1704

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

Center for Genetic Engineering and Biotechnology (CIGB)

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:

Trials notification

Regulatory instance:

Center for State Control of Drugs, Medical Devices and Equipment (CECMED)

Notification date :

10/03/2018

Reference number:

37.001.18BF4

Principal investigator

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

First name:

Lourdes

Midle name:

Petronila

Last name:

Perez Camejo

Medical Specialty :

Medical Doctor, 1st degree Specialist in Gastroenterology

Affiliation:

General Provincial Hospital "Camilo Cienfuegos"

Postal address:

Bartolome Masso No. 128

City:

Sancti Spiritus

Country:

Cuba

Zip Code:

60100

Telephone:

+53-4124017

Email address:

lpcamejos.ssp@infomed.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:

Pinar del Rio, Hospital “Abel Santamaria”, Dr. Guillermo Fernandez Maqueira. 1st degree Specialist in Gastroenterology

La Habana, Gastroenterology Institute, Dr. Zaily Dorta Gurudi, 2nd degree Specialist in Gastroenterology

Ciego de Avila, Hospital “Antonio Luaces”, Dr. Alberto Martinez Sarmiento. 1st degree Specialist in Gastroenterology

Holguin, Hospital “Lucia Iñiguez”, Dr. Carmen del Pilar Sierra Peña. 1st degree Specialist in Gastroenterology

Santiago de Cuba, Hospital “Juan Bruno Zayas”, Dr. Daisy Marten Mareas. 1st degree Specialist in Gastroenterology

Santiago de Cuba, Hospital “Saturnino Lora”, Dr. Sergio del Valle. 1st degree Specialist in Gastroenterology

Research ethics committees:

General Provincial Hospital "Camilo Cienfuegos". Approval date: January 18, 2018

Hospital “Abel Santamaria”. Approval date: March 2, 2018.

Gastroenterology Institute. Approval date: March 2, 2018.

Hospital “Antonio Luaces”. Approval date: February 5, 2018.

Hospital “Lucia Iñiguez”. Approval date: January 25, 2018.

Hospital “Juan Bruno Zayas”. Approval date: January 25, 2018.

Hospital “Saturnino Lora”. Approval date: January 30, 2018.

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

06/08/2018

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 Virus infection

Health condition(s) code:

Hepatitis B, Chronic

Hepatitis B

Hepadnaviridae Infections

DNA Virus Infections

Virus Diseases

Hepatitis, Viral, Human

Hepatitis, Chronic

Hepatitis

Liver Diseases

Digestive System Diseases

Intervention(s):

All patients will receive HeberNasvac® according to the vaccine package insert: Schedule: 0-2-4-6-8-12-14-14-18-18-20 weeks First cycle: HeberNasvac® intranasal dispersant: (0.10 mg HBsAg + 0.10 mg HBcAg) / 1.0 mL dose. One dose is applied every two weeks until completing 5 doses. Second cycle (One month after the end of the first cycle): HeberNasvac® intranasal dispersant: (0.10 mg of HBsAg + 0.10 mg of HBcAg) / dose of 1.0 mL and simultaneously HeberNasvac® for subcutaneous injection: (0.10 mg of HBsAg + 0.10 mg of HBcAg) / dose of 1.0 mL. One dose of each is applied every two weeks until the combined 5 doses of both administration routes are completed. Duration of treatment: 20 weeks

Intervention code:

Hepatitis B Surface Antigens

Immunotherapy, Active

Vaccines, Synthetic

Administration, Intranasal

Nasal Sprays

Intervention keyword:

HeberNasvac

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):

Clearance of HBsAg in serum (Qualitative determination of HBsAg by UltramicroELISA (UMELISA HBsAg)). Measurement time: At baseline and, weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240.

Key secondary outcomes:

1. Percentage of patients with decreased viral load (HBV DNA) below the limit of detection during follow-up with respect to time zero (Quantification of HBV DNA. Polymerase Chain Reaction (PCR) to detection and quantification of HBV). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240 2. Percentage of patients with significant reduction in viral load in at least 1 log HBV DNA in any of the follow-up extractions with respect to time zero (Quantification of HBV DNA. Polymerase Chain Reaction (PCR) to detection and quantification of HBV). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240 3. Percentage of patients with suppression of viral load, HBV DNA below 10 000 copies / ml considering viral load at the beginning of treatment (Quantification of HBV DNA. Polymerase Chain Reaction (PCR) to detection and quantification of HBV). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240. 4. Percentage of HBeAg loss in positive HBeAg patients at the start of treatment (HBeAg detection, ELISA HBeAg/anti-HBe (Commercial kit)).Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240 5. Percentage of seroconversion to HBeAg in positive HBeAg patients at the start of treatment (HBeAg, Anti-HBe ELISA HBeAg/anti-HBe (Commercial kit)). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240. 6. Percentage of patients with significant reduction in the quantification of HBsAg (Quantification of HBsAg. Household ELISA using UMELISA HBsAg, (Commercial kit) and, a commercial standard for the quantification curve). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240 7. Percentage of seroconversion to HBsAg (HBsAg detection (qualitative), UltramicroELISA to detect HBsAg (Commercial kit), Anti-HBs detection. ELISA Anti-HBs (Commercial kit)).Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240 8. Biochemical response (Given by sustained normalization of the serum alanine aminotransferase enzyme (ALAT)). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240. 9. Clinical adverse events (The type, duration, intensity, imputability, conduct followed and result after each immunization will be described. Adverse Event Active observation of patients for 1 hour at the clinical site).Measurement time: 0-2-4-6-8-12-14-16-18-20 weeks. 10. Evaluation of hematological and liver function variables (Complete blood count and Blood biochemistry). Measurement time: Before the start of treatment and in weeks 12, 24, 48, 72, 96, 120, 144, 168, 192, 216 and 240

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:

None

Inclusion criteria:

1. Male or female subjects ≥ 18 years of age. 2. Documented chronic hepatitis B determined by HBsAg + for more than 6 months. 3. Voluntariness of the patient to participate expressed by delivery of signed informed consent.

Exclusion criteria:

1. Evidence or suspicion of hepatocarcinoma and/or liver cirrhosis by clinical/sonography. 2. Clinical, sonographic or serological evidence of decompensated liver disease (gastrointestinal bleeding, hepatic encephalopathy, ascites, spontaneous peritonitis, hepato-renal syndrome, ALT greater than 500 IU / L). 3. History of liver transplantation. 4. Have received antiviral therapy for chronic hepatitis B (IFN, PEG-IFN, or nucleos(t)ide analogue) in the 6 months prior to inclusion. 5. Immunosuppressive therapy in the six months prior to the screening visit. 6. History of allergy to any of the ingredients of the vaccine. 7. Pregnancy, breast feeding or female subjects who do not use contraceptive methods or who plan a pregnancy that coincides with the course of treatment. 8. Presence of mental and / or psychiatric disorders that make it impossible to sign informed consent or patient follow-up.

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:

N/A: single arm study

Masking:

Open

Control group:

Uncontrolled

Study design:

Single group

Phase:

4

Target sample size:

300

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:

Pablo

Middle Name:

Arsenio

Last Name:

Diaz Reyes

Specialty:

Medical doctor, specialist of 1st degree in Neonatology

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31 entre 158 y 190, Cubanacan, Playa.

City:

Havana

Country:

Cuba

Zip Code:

10600

Telephone:

+53-72087465

Email :

pablo.dias@cigb.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:

Zurina

Last Name:

Cinza Estevez

Specialty:

Medical doctor, Specialist of 1st degree in Clinical Biochemistry.

Affiliation:

Center for Genetic Engineering and Biotechnology (CIGB).

Postal Address:

Ave. 31/ 158 and 190, Cubanacan, Playa.

City:

Havana

Country:

Cuba

Zip Code:

10600

Telephone:

+53-72087421

Email :

zurina.cinza@cigb.edu.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:

RPCEC00000283

Date of Registration in Primary Registry:

03/08/2018

Record Verification Date:

2020/12/21

Next update date:

2021/12/21

Link to the spanish version:

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HeberNasvac® Phase IV in Chronic Hepatitis B

About the RPCEC

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