Trial Information

Randomized Clinical Study of Arabinoxylan Rice Bran (MGN-3/Biobran) for the Treatment of Hepatocellular Carcinoma and Hepatitis B and C Infection

Objective(s): The objective of this study is to analyze a data from a study that examined
the biotherapeutic effect of combining conventional therapy in the presence of
MGN-3/Biobran. The study focused on treatment of patients in Vietnam with hepatocellular
carcinoma (HCC) and Hepatitis B and C.

Purpose of the study:

Aim 1: The biotherapeutic effect of combining conventional therapy and a natural, non-toxic
arabinoxylan rice bran (MGN-3/Biobran) for the treatment of patients with HCC will be
examined. Parameters under investigation include, lifespan of the patient, progression of
the disease (tumor size), and recurrence of the disease.

Aim 2: The biotherapeutic effect of combining conventional therapy and a natural, non-toxic
arabinoxylan rice bran (MGN-3/Biobran) for the treatment of patients with Hepatitis B virus
(HBV) will be examined. Parameters under investigation include alanine transaminase (ALT)
levels, HBV antigen levels, and HBV DNA levels.

Methodology:

Study Design:

Secondary analysis of data from "The effects of Biobran/Lentin Plus in the adjuvant therapy
of hepatocellular carcinoma and chronic hepatitis B" study. The study was a randomized
controlled design that was conducted from 6/2006 to 7/2008 at the 108 Military Central
Hospital, Hanoi, Vietnam with Dr. Mai Hong Bang as the Principal Investigator. MGN-3/Biobran
was approved by Vietnam Ministry of Health with import VISA No.12577/2005/CBCL-YT.
Therefore, The 108 Military Central Hospital approved the study for treatment of patients
with HCC and hepatitis B too.

1. Hepatocellular Carcinoma (HCC): Sixty-eight patients of both sexes, male and female,
with HCC were divided into two groups: group 1 (38 patients) was treated with
conventional therapy plus MGN-3 for 3 years, and group 2 (30 patients) was treated with
conventional therapy alone. At various intervals and at the end of the study patients
were assessed for the following: lifespan of the patient, progression of the disease
(tumor size), and recurrence of the disease.

2. Hepatitis B virus (HBV): Sixty-two patients of both sexes, male and female, with HBV
were divided into two groups: group 1 (32 patients) was treated with conventional
therapy plus MGN-3 for 3 years, and group 2 (30 patients) was treated with conventional
therapy alone. Conventional therapy given was the anti-viral drug, Entecavir.

Data were collected every six months for two years. Parameters under investigation
included: alanine transaminase (ALT) levels, HBV antigen (HeBAg), and HBV DNA levels.

Patients were treated with standard treatment (transarterial oily chemoembolization
(TOCE) for HCC; Entecavir for HBV) in combination with the experimental treatment,
arabinoxylan rice bran (MGN-3/Biobran) and compared with a control group given standard
treatment alone. Standard treatment was administered for 3 years. The experimental
treatment (MGN-3/Biobran) was administered at a dose of 1g/day for 3 years.

Patient characteristics and measures:

- Group: two groups Group1 = Conventional therapy Group2 = Conventional therapy +
MGN-3

- Age range of the patients: 30-68 years old

- Gender: male and female

- Medical condition(s):

Hepatitis infection:

Hepatitis B: HCC HBV Hepatitis C: HCC Hepatitis B and C: HCC

- Number of tumors/patient (HCC study)

- Tumor size (HCC study): was measured in cm. <3 cm 3-6cm >6cm

- AFP level: HCC - ≤500 ng/ml >500 ng/ml

- HBV viral load

- ALT level: HCC

- HBV <100 IU/ml 100-250 IU/ml: 37 patients >250 IU/ml: 15 patients

- Tumor Recurrence

- Patient Survival

Intervention details Treatment group(s): HCC - Intervention only (PEIT, TOCE, PEIT +
TOCE, TOCE + RFA) Intervention + MGN-3 HBV - Intervention only (Entecavir)
Intervention + MGN-3 Control(s): Intervention only group served as a control
Co-interventions: Intervention + MGN-3 group Duration of intervention: HCC - 3 years
HBV - 2 years

Who delivered intervention? Dr. Mai Hong Bang and some other doctors. A consultation
before delivering intervention for all patients

Outcome measures HCC: ALT level, AFP level, tumor size, patient survival, recurrence
HBV: ALT level, HBV DNA level, recurrence, patient survival, HBeAg seroconversion

Methods of assessing outcome measures:

ALT and AFP levels, HBV DNA level, HBeAg seroconversion: blood test Tumor size:
ultrasonography and radiography Patient survival: observation

When were they measured? Every 6 months Length of follow-up: HCC - 3 years HBV - 2
years

Inclusion criteria:

HCC patient Criteria of inclusion - Patient had ≤3 tumors (1 tumor under 12cm/ or 2
tumor under 5cm /or 3 tumor under 3cm) - Stage of disease: Okuda I,II and Child Pugh
A,B

- Liver biopsy: HCC positive

- General condition: average/ good

Chronic hepatitis B patient Criteria of inclusion

- Patient have been carrying HBsAg over 6 months

- ALT was over or equal 2 times ULN

- HBV-DNA level: 104 (log10 copies/ml) with HBeAg(-) patient and 105 (log10
copies/ml) with HBeAg(+) patient

Exclusion criteria:

HCC patient Criteria of exclusion - Tumor size is too big (over 12 cm), multiple tumors
(over 3 tumors or diffuse tumor type) - Prothrombin under 60%

- Severe liver or/ and renal insufficiency

- Portal vein body thrombosis

Chronic hepatitis B patient Criteria of exclusion

- Used immunotherapy or corticotherapy for 6 months

- Pregnant woman

Procedures: Upon approval by IRB, the data will be analyzed using statistical analysis
and the data will be published in a peer-reviewed journal, as this data has not yet
been published. We will receive the data from the PI (Dr. Mai Hong Bang, MD Ph.D.,
Associate Professor, Department of Hepatogastroenterology). After receiving the IRB
approval, we will conduct secondary analysis of the data. We will receive the data as
an electronic file excel file format with the code book for all the variables. We will
do frequency and data checking and data management to prepare the data for analysis. We
will do recoding and create new variables from the existed variables as a way to
prepare for the data analysis.

Benefits to subjects: Conventional therapies for HCC and HBV, in addition to their
toxicity, do not substantially improve the survival rate of the patients. The
combination of MGN-3/Biobran with these conventional therapies may improve the survival
rate of the patients and decrease the rate of recurrence.

Benefits to the Community: There is a disproportionately high incidence of HCC in
developing countries, and over 50% of HCC cases occur in Asia. Hepatitis B is closely
linked to liver cancer, which is almost always fatal. It is estimated that nearly 80%
of all liver cancer worldwide is caused by hepatitis B infection. Therefore, there is
a need for new treatments with minimal to no side effects to combat these diseases.
This study will determine the potential of MGN-3/Biobran combined with conventional
therapy to improve the outcome of these diseases.