NASVAC Phase II Trial in patients with Chronic Hepatitis B Virus infection

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:

“A phase IIa-IIb placebo-controlled, randomized, clinical trial to assess the efficacy and safety of NASVAC Therapeutic Vaccine Candidate in patients with Chronic Hepatitis B Virus infection”

Secondary indentifying numbers:

IG/VHS/HB/1103

Issuing authority of the secondary identifying numbers:

Center for Genetic Engineering and Biotechnology (CIGB)

Source(s) of monetary or material support:

HeberBiotec S.A.

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 the Quality of Drugs(CECMED)

Reference number:

Pending

Principal investigator

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

First name:

Daisy Martén Mareas, MD. 1st. Degree Gastroenterology Specialist, MSc. in Infectious Diseases

Last name:

Not entered

Affiliation:

Not entered

Postal address:

Not entered

City:

Not entered

País:

Not entered

Zip Code:

Not entered

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:

Cuba

Clinical sites:

Villa Clara, “Arnaldo Milián Castro” University Hospital, Yosvany Medina Garrido, MD. 1st Degree MGI & Gastroenterology Specialist, Assistant Professor Cienfuegos, “Gustavo Aldereguía Lima” University Hospital, Yagen María Pomares Pérez, MD. 1st Degree MGI & Gastroenterology Specialist Sancti Spiritus, “Camilo Cienfuegos” Medical and Surgical Hospital, Lourdes Pérez Camejo, MD. 1st Degree Gastroenterology Specialist Ciego de Ávila, “Antonio Luaces Iraola” University Hospital, Alberto Martínez Sarmiento, MD. 1st Degree Gastroenterology Specialist, MSc. in Infectious Diseases, Assistant Professor Las Tunas, “Dr. Ernesto Guevara de la Serna” General Provincial Hospital, Liem Fonseca Chong, Md. 1st Degree Gastroenterology Specialist, MSc. in Natural and Bioenergetic Medicine, Assistant Professor Holguín, “Lucía Íñiguez Landín” Medical and Surgical Hospital, Ranier Nelson Pupo Carracedo, MD. 1st Degree Gastroenterology Specialist, MSc. in Emergency Medicine, Assitant Professor Granma, “Carlos Manuel de Céspedes” University Hospital, Bayamo, Yoel Mario Ricardo Serrano, MD. 1st Degree Gastroenterology Specialist, MSc. in Infectious Diseases, Assistant Professor Granma, “Celia Sánchez Manduley” Provincial Medical-Surgical Hospital, Manzanillo, Andrés Andino Luján, MD. 1st Degree MGI & Gastroenterology Specialist Guantanamo, “Dr. Agostinho Neto” University Hospital, Yamilet Calzadilla Navarro, MD. 1st Degree Gastroenterology Specialist, MSc. in Infectious Diseases, Assistant Professor Santiago de Cuba, ¨Saturnino Lora¨ Provincial Hospital, Lissette Espinosa Martín, MD. 2nd Degree Internal Medicine Specialist, MSc. in Infectious Diseases and Diagnostic Media, Assistant Professor

Research ethics committees:

Santiago de Cuba, General University Hospital “Dr. Juan Bruno Zayas Alfonso”, 06.12.2011 Villa Clara, “Arnaldo Milián Castro” University Hospital, 07.12.2011 Cienfuegos, “Gustavo Aldereguía Lima” University Hospital, 05.05.2012 Sancti Spiritus, “Camilo Cienfuegos” Medical and Surgical Hospital, 28.03.2012 Ciego de Ávila, “Antonio Luaces Iraola” University Hospital, 07.03.2012 Las Tunas, “Dr. Ernesto Guevara de la Serna” General Provincial Hospital, 13.03.2012 Holguín, “Lucía Íñiguez Landín” Medical and Surgical Hospital, 28.03.2012 Granma, “Carlos Manuel de Céspedes” University Hospital, Bayamo, 05.03.2012 Granma, “Celia Sánchez Manduley” Provincial Medical-Surgical Hospital, Manzanillo, 30.11.2011 Guantanamo, “Dr. Agostinho Neto” University Hospital, 23.01.2012 Santiago de Cuba, ¨Saturnino Lora¨ Provincial Hospital, 05.03.2012

Recruitment status

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

Recruitment status:

Pending

Date of first enrollment:

02/12/2012

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

Intervention(s):

Group I (Experimental): NASVAC Vaccine, dose 100 mcg=1mL, Cycle 1 of treatment [NASVAC Intranasal, 5 doses]: weeks 0, 2, 4, 6 and 8; Cycle 2 of treatment [NASVAC Intranasal+subcutaneous, 5 doses]: weeks 17, 19, 21, 23 and 25 Group II (Experimental): NASVAC Vaccine, 100 mcg=1mL, Cycle 1 of treatment [NASVAC Intranasal, 10 doses]: weeks 0, 1, 2, 3, 4, 5, 6, 7, 8, 9; Cycle 2 [NASVAC Intranasal+subcutaneous, 10 doses]: weeks 17, 18, 19, 20, 21, 22, 23, 24, 25 and 26 Group III (Experimental): NASVAC Vaccine, 100 mcg=1mL, subcutaneous route, 5 dose schedule: weeks 17, 19, 21, 23 and 25 Group IV (Experimental): NASVAC Vaccine, 100 mcg=1mL, subcutaneous route, 10 dose schedule: weeks 17, 18, 19, 20, 21, 22, 23, 24, 25 and 26 Group V (Control): 0.9% Physiologic Saline Solution, 1mL dose, Cycle 1 of treatment [Intranasal, 10 doses]: weeks 0, 1, 2, 3, 4, 5, 6, 7, 8 and 9; Cycle 2 of treatment [Intranasal+subcutaneous, 10 doses]: weeks 17, 18, 19, 20, 21, 22, 23, 24, 25 and 26

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):

HBV viral load negativization (reduction below = 300 copies of HBV DNA/mL) in sera. Measuring time: weeks 12, 30, 42, 54, 66, 78, 104 and 130 of follow up

Key secondary outcomes:

Significant reduction in viral load (= 1log HBV DNA). Measuring time: weeks 12, 30, 42, 54, 66, 104 and 130 of follow up HBeAg negativization %. Measuring time: weeks 12, 30, 42, 54, 66, 78, 104 and 130 of follow up HBeAg seroconversion %. Measuring time: weeks 12, 30, 42, 54, 66, 78, 104 and 130 of follow up Sustanined normalization % in serum alanina-aminotransferase enzyme (ALT). Measuring time: weeks 12, 30, 42, 54, 66, 78, 104 and 130 of follow up HBsAg seroconversion %. Measuring time: weeks 12, 30, 42, 54, 66, 78, 104 and 130 of follow up HBsAg stimulation index. Measuring time: weeks 0, 12 and 28 of follow up Proportion of AE in the subjects (yes/no). Measuring time: In every administration and overall AE description (Name of the adverse event) AE duration (date difference between AE beginning and ending) AE Intensity (Slight, Moderate, Severe) AE Seriousness (Serious/Grave, Non serious/Non grave) Action taken regarding study treatment (without changes, dose modification, temporal withdrawal or definitive suspension of the treatment under study) AE outcome (recovered, improved, persisting or with sequelae) Causality relationship (1.Very likely, 2. Probable, 3.Possible, 4.Unlikely, 5.Non related, 6.Not evaluable)

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:

65 years

Inclusion criteria:

1.Aged 18-65 years, male or female 2.History of Chronic Hepatitis B determined by HBsAg+ longer than 6 months 3.Serum viral load HBV DNA greater than = 104 copies/ml at the screening visit (or until 12 weeks prior inclusion) 4.CHB patients with no therapeutic option (refractory, intolerant or patients reluctant to fulfill cuban standard treatment for this disease are allowed to enter the study) or treatment naïve patients with ALAT levels below or equal to = 2.0 x the upper limit of normality range (ULN) of the lab at screening 5.Serum alpha fetoprotein (AFP) < 50 ng/mL at the first screening visit. 6.Compensated liver disease with the following laboratory and clinical parameters at study screening: a)No history of variceal bleeding. b)No history of encephalopathy. c)No history of ascites d)Adequate renal function defined as serum creatinine = 1.5 mg/dL (= 130 µmol/L). e)Total leukocyte count = 3.0 x 109/L; Platelets = 80 x 109/L; Hemoglobin = 10 g/dL(males) or = 9 g/dL (females); TBil=1.5ULN or or normal direct bilirubin ; ALB = lower limit of normality (LLN); Prothrombin time (PT): elongation = 3 second above normal range; Fasting blood glucose=7.0mmol/L 7.Uses contraception for female subjects with child-bearing potential 8.Agree not to participate in any other investigational trials or to undertake other HBV systemic antiviral regimens during participation in this trial. 9.Able to give written informed consent and comply with the requirements of the study

Exclusion criteria:

1.History of antiviral therapy for chronic hepatitis B in the 6 months prior inclusion 2.Positivity for serologic markers of hepatitis C virus or Human immunodeficiency virus (HIV-1,2) infection. 3.Hepatocarcinoma, suspected hepatocarcinoma or hepatic cirrhosis by clinic/sonography 4.Clinical, sonographic or serologic evidences of decompensate liver disease (gastrointestinal bleeding, hepatic encephalopathy, ascites, spontaneous peritonitis, hepato-renal syndrome, ALAT greater than 10 folds the ULN). 5.Clinical history of concomitant hepatopathy of any aetiology: Alcoholism, Autoimmune hepatitis, Toxic Hepatitis, Wilson’s Disease, Haemochromatosis. 6.Acute or chronic disease of the respiratory airways and perinasal sinuses (eg. nasal cavity, nostril and nasal septum malformations, recurrent epistaxis, severe allergic rhinitis, rhinopharingitis, sinusitis, nasal polyps, bronchial asthma, etcetera) 7.Has any of the following acute or chronic clinically significant (decompensate) disease inappropriate for participation in the study based on the investigator's judgment. [Eg, Cardiovascular system: cardiopathy, myocardial infarction, congestive heart failure, angina pectoris, severe hypertension, significant arrhythmia); Endocrine: (uncontrolled metabolism diseases such as Diabetes mellitus, uncontrolled thyroid diseases, etc); Renal: (Kidney failure); Others: autoimmune disorders (lupus, colagenosis, Rheumatoid arthritis, Multiple Sclerosis), uncontrolled epilepsy, active tuberculosis, malignancies (e.g.tumor), psychiatric disease or severe mental depression]. 8.Immunosuppressive treatment within 6 months of Screening Visit [eg: chemotherapy, radiotherapy, steroids at high doses (=20 mg per day of prednisone or its equivalent longer than 2 weeks)]. The use of topical or intra-(articular/bursal/tendon) corticosteroids will not be considered a contraindication. 9.Malignancy other than curatively treated, superficial skin cancer or carcinoma in situ of the cervix. 10.Participation in any experimental protocol or antihepatitis B vaccination or therapy within 6 months prior to the Screening Visit. 11.History of severe allergy (Grade III or IV Asthma, urticaria, severe dermatitis or bronchitis) or suspected allergy to the ingredients of the study drug 12.Female who is in pregnancy, puerperium, in lactation or women of childbearing potential that do not use methods of contraception or are planning to become pregnant during the course of the study. 13.Has a history of alcohol abuse (Alcohol consumption for more than 5 years, with daily consumption over 40g for males and over 20g for females) and known drug dependence. 14.Has a history of organ transplant (except external corneal transplantation and hair transplantation) 15.Hemoglobin levels = 9 g/dL (females) or = 10 g/dL(males), or Platelets = 80 x 109/L, Global leukocyte count = 12x109/L or =3.0 x109/L. 16.History of mental or psychiatric disorders in a way that the patients is not able to give written informed consent or cannot comply with the requirements of the study 17.Any other factor inappropriate for enrollment in the study or study completion in the view of the investigator.

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:

Randomized controlled trial

Masking:

Double Blind

Control group:

Placebo

Study design:

Factorial

Phase:

Target sample size:

160

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:

Arístides

Last Name:

Aguilar-Betancourt

Affiliation:

Center for Genetic Engineering and Biotechnology

Postal Address:

31 Ave. b/ 158 y 190 Cubanacán, Playa, PO Box 6162

City:

Havana

País:

Cuba

Zip Code:

16040

Telephone:

(53-7)-2087442

Email :

aristides.aguilar@cigb.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:

Arístides

Last Name:

Aguilar-Betancourt

Affiliation:

Center for Genetic Engineering and Biotechnology

Postal Address:

31 Ave. b/ 158 y 190 Cubanacán, Playa, PO Box 6162

City:

Havana

País:

Cuba

Zip Code:

16040

Telephone:

(53-7)-2087442

Email :

aristides.aguilar@cigb.edu.cu [2]

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:

RPCEC00000137

Date of Registration in Primary Registry:

2012-10-12

Record Verification Date:

2012-09-18 20:00

Link to the spanish version:

Click here [3]