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

• Register: RPCEC
• Last refreshed on: 27 May 2013
• Main ID: RPCEC00000137
• Date of registration: 12/10/2012
• Primary sponsor: Center for Genetic Engineering and Biotechnology (CIGB)
• Public title: NASVAC Phase II Trial in patients with Chronic Hepatitis B Virus infection
• 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”
• Date of first enrolment: 02/12/2012
• Target sample size: 160
• Recruitment status: Pending
• URL: http://registroclinico.sld.cu/trials/RPCEC00000137-En
• Study type: Interventional
• Study design: Randomization: Randomized Controlled Trial Blinding: Double Blind Placebo: Placebo Assignment: Factorial Purpose: Treatment

Countries of recruitment

Cuba

Contacts

• Name: Arístides Aguilar-Betancourt
• Affiliation: Center for Genetic Engineering and Biotechnology

• Name: Arístides Aguilar-Betancourt
• Affiliation: Center for Genetic Engineering and Biotechnology

Key inclusion & exclusion criteria

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.

Age minimum: 18 years
Age maximum: 65 years
Gender: Both

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

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

Secondary Outcome(s)

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)

Secondary ID(s)

IG/VHS/HB/1103

Source(s) of Monetary Support

HeberBiotec S.A.

Secondary Sponsor(s)

Ministry of Public Health (MINSAP), CUBA