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Trial registered on ANZCTR


Registration number
ACTRN12612000828820
Ethics application status
Approved
Date submitted
6/08/2012
Date registered
7/08/2012
Date last updated
17/10/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study of the safety of combining BIT225 with pegylated interferon and ribavirin, in patients with hepatitis C virus infection, including measurement of the concentration and distribution of BIT225 in the body and antiviral activity.
Scientific title
A Phase 2a, Placebo-Controlled, Randomised Study of the Safety, Pharmacokinetics and Antiviral Activity of BIT225 in Combination with Pegylated Interferon and Ribavirin in Patients with Hepatitis C Virus Infection.
Secondary ID [1] 280973 0
BIT225-005
Universal Trial Number (UTN)
U1111-1133-2539
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C Virus Infection 287085 0
Condition category
Condition code
Infection 287413 287413 0 0
Other infectious diseases
Oral and Gastrointestinal 287424 287424 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BIT225 200mg or 400mg, or placebo, once daily on days 0 and 28, and twice daily on days 1 to 27. BIT225 is supplied as a powder to be suspended immediately before use in 25mL of Orasweet Sugar Free, a taste masking agent. All participants will also receive standard of care therapy for Hepatitis C Virus (HCV) of pegylated interferon (alfa-2a or alfa-2b) (PEG-IFN) 180mg/week by subcutaneous injection and oral ribavirin (RBV) 1000-1200mg/day (weight based) for 48 weeks.
Intervention code [1] 285419 0
Treatment: Drugs
Comparator / control treatment
Placebo is 200mg or 400mg of lactose to be suspended immediately before use in 25mL of OraSweet Sugar Free, a taste masking agent.
Control group
Placebo

Outcomes
Primary outcome [1] 287676 0
Evaluate the safety and tolerability of 200 and 400 mg of BIT225 twice daily compared with placebo in combination with PEG-IFN and RBV in patients with chronic HCV infection that are treatment-naive to antiviral treatment with ribavirin and/or interferon. Safety and tolerability will be assessed by comparison to placebo of treatment emergent untoward medical changes, e.g. nausea, vomitting or loss of weight, and changes in clinical laboratory assessments, vital signs and ECG.
Timepoint [1] 287676 0
Medical changes will be evaluated daily, clinical laboratory assessments, vital signs and ECG weekly, over the 28 days of dosing.
Secondary outcome [1] 298619 0
Evaluate the pharmacokinetics of 200 and 400 mg of BIT225 administered daily on Day 0 and Day 28 and twice daily on Days 2 - 27 for 28 consecutive days in combination with PEG-IFN and RBV in patients with chronic HCV infection.
Timepoint [1] 298619 0
Pharmacokinetic samples will be collected on Day 0 and Day 28 at 0 hour (pre-dose), 30, 60, 90, 120, 150 minutes post-dose, then at 3, 4, 5, 6, 8, 10, 12, 14, 16 and 24 hours post-dose. Blood samples will also be collected pre-dose on Days 7, 14, and 21. The concentration of BIT225 in plasma will be measured using a validated liquid chromatography tandem mass spectometry method.
Secondary outcome [2] 298620 0
Evaluate the antiviral activity of BIT225 administered for 28 consecutive days in combination with PEG-IFN and RBV in patients with chronic HCV infection that are treatment-naive to antiviral treatment with ribavirin and/or interferon.
Timepoint [2] 298620 0
Blood samples for HCV RNA assays will be collected at Screening, Day -14 and Day -1, Day 0 pre-dose (0 hour), 4 and 12 hours post-dose, Days 1, 7, 14, 21, 28 and in follow up at Months 2, 3, 12 and 18.
Qualitative HCV RNA assessment (Roche COBAS Amplicor HCV Test, version 2.0) will be performed at the Screening visit. A quantitative test will be performed on all positive qualitative tests at this visit. HCV RNA will be detected by qualitative RT-PCR with Cobas AMPLICOR HCV Test, version 2.0 (Roche Diagnostics, Branchberg, NJ, USA). HCV viral load will be determined by COBAS AmpliPrep/COBAS TaqMan HCV Test (Roche). HCV RNA measurements performed at subsequent study visits will use the quantitative test only.

Eligibility
Key inclusion criteria
1. Males or females, aged 18 to 55 years

2. Chronic hepatitis C infection (defined as persistent HCV infection as diagnosed by detection of HCV RNA in the blood at least 6 months from initial detection).

3. Serologic evidence of HCV infection by anti-HCV antibody test.

4. Documentation of HCV genotype 1-infection at any time prior to entry. A laboratory report must be used for documentation. Those without known genotype at screening will have a screening genotype performed.

5. HCV RNA of >/= 105 IU/mL as measured by the ROCHE COBAS Amplicor Monitor 'registered trademark' version 2.0 method within 60 days of Entry

6. ALT (SGOT) , AST (SGPT), and alkaline phosphatase less than or equal to 5 times upper level of normal within 60 days of Entry.

7. For females of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or tubal ligation), must have a negative serum or urine pregnancy test with a sensitivity of at least 50mlU/mL within 60 days prior to study entry.
A negative serum or urine pregnancy test result is also required within 24 hours prior to the initiation of study treatment (Day -1)

All subjects must agree not to participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization).
If participating in sexual activity that could lead to pregnancy, the subject must agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 6 weeks after stopping study treatment.

8. Subjects who are not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or have undergone hysterectomy, salpingotomy, and/or bilateral oophorectomy or men who have documented azoospermia) are eligible without requiring the use of contraceptives.

9. Provide written informed consent to participate in the study and be willing to comply with the study procedures.

10. Naive to therapy for HCV, including any interferon or ribavirin.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients who have received an investigational drug for HCV.

2. Positive results for Hepatitis B (Hepatitis B surface antigen) and HIV antibody at Screening.

3. History or presence of other evidence of a medical condition associated with chronic liver disease (e.g., chronic or acute hepatitis B, acute hepatitis A, hemochromatosis, autoimmune hepatitis, Wilson’s disease, Gilbert’s syndrome, homozygote alpha1-antitrypsin deficiency, alcoholic liver disease, and toxin exposures).

4. Bridging cirrhosis or cirrhosis confirmed on a biopsy obtained within the past 36 months as judged by a local pathologist. Note: patients with Metavir (or equivalent index) stage 3 fibrosis on a previous biopsy or patients with no previous biopsy will require an abdominal ultrasound within 6 months of first dose showing no evidence of cirrhosis

5. History or signs of decompensated liver disease manifested by presence of Child-Pugh class B or C, ascites, variceal bleeding, or hepatic encephalopathy, spontaneous bacterial peritonitis, or other clinical signs of portal hypertension or hepatic insufficiency

6. History or other evidence of clinically significant renal disease.

7. Pregnancy or breast feeding, male partners of pregnant females.

8. Abnormal haematological and biochemical parameters within 60 days of Entry:
a. Absolute neutrophil count <1000/mm3
b. Haemoglobin <11 g/dL in females or 13 g/dL in males
c. Platelet count <150,000/mm3
d. International normalized ratio (INR) >1,5
e. Total bilirubin within normal reference range
f. Creatinine > 1.5 mg/dL
Estimated creatinine clearance < 80 mL/minute at Screening. Value will be calculated using the Cockcroft-Gault formula.

9. Screening ECG QTcB value >/= 450 ms.

10. The consumption / administration of prohibited concomitant medication (prescribed, over-the-counter or complementary) at the time of the Screening visit. Any medication taken from 28 days prior to first dose through to the end of the participation in the study must be approved by the Biotron Medical Monitor in consultation with the Investigator.

11. Active drug or alcohol use or dependence that, in the opionion of the site investigator, would interfere with adherence to study requirements.

12. A positive result on urine screen for drugs of abuse and alcohol breath test at Screening or Day -1 which in the opinion of the Investigator should preclude them from participation in the study.

13. History of severe psychiatric disease, which in the opinion of the Investigator should preclude them from participation in the study. Uncontrolled or active depression or other psychiatric disorder such as untreated Grade >/=3 psychiatric disorder, Grade >/=3 disorder not amenable to medical intervention, or any hospitalization within the past 52 weeks that in the opinion of the site investigator might preclude tolerability of study requirements.

14. Any prior suicide attempt.

15. History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis requiring more than intermittent non-steroidal anti-inflammatory medications for management, etc.) that may be exacerbated by interferon use.

16. History or other evidence of chronic pulmonary disease associated with functional limitation.

17. History of documented or presumed coronary artery disease or cardiovascular disease, clinically significant arrhythmia.

18. History of a severe seizure disorder or current anticonvulsant use.

19. History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC, such as suspicious foci on imaging studies or elevated serum alpha-fetoprotein >50 ng/mL.

20. History of having received any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) within 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.

21. History of major organ transplantation with an existing functional graft.

22. Active thyroid disease (use of thyroid hormone replacement therapy permitted by TSH or free T4 must be in normal range.) Any patient with a baseline increased risk for anaemia (e.g. thalassemia, spherocytosis, history of Gastrointestinal bleeding, etc) or for whom anaemia would be medically problematic.

23. History or other evidence of severe retinopathy.

24. Serious illness requiring systemic treatment and/or hospitalization within 24 weeks prior to entry; serious illness including malignancy, active coronary artery disease within 24 weeks prior to study entry; or other chronic medical conditions that may preclude completion of the protocol in the CRS investigator’s opinion. Such conditions may be discussed with the protocol chair/vice chair.

25. Known allergy/sensitivity oh any hypersensitivity to components of study drug or its formulation.

26. Heavy smokers (> 10 cigarettes per day) who are unable to refrain from smoking during the confinement periods in this trial.

27. Difficulty abstaining from grapefruit and grapefruit containing products from 7 days prior to the first dose of investigational product until the end of the dosing period.

28. Difficulty abstaining from high consumption of >2 cups coffee/tea/caffeine containing soft drinks per day.

29. Participation in a clinical study with an investigational drug, biologic, or device within 3 months prior to anticipated dose administration.

30. Current use of herbal medications or unwillingness to cease use during study participation.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be assigned to a sequentially numbered treatment in accordance with the randomisation schedule following confirmation of eiligibility on day 0. An unblinded pharmacist at the site will dispense the medication to the blinded site staff according to the randomisation schedule. The dispensed medication will carry the participant's unique study number.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
3 block randomisation algorithm
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Allocation to treatment is in a ration of 1:1:1.
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/11/2010
Actual
23/11/2010
Date of last participant enrolment
Anticipated
Actual
28/06/2011
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 4459 0
Thailand
State/province [1] 4459 0

Funding & Sponsors
Funding source category [1] 285755 0
Commercial sector/Industry
Name [1] 285755 0
Biotron Limited
Country [1] 285755 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Biotron Limited
Address
Suite 1.09
56 Dehli Road
North Ryde NSW 2113
Country
Australia
Secondary sponsor category [1] 284585 0
None
Name [1] 284585 0
Address [1] 284585 0
Country [1] 284585 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287768 0
Siriraj Institutional Review Board, Faculty of Medicine, Mahidol University
Ethics committee address [1] 287768 0
Ethics committee country [1] 287768 0
Thailand
Date submitted for ethics approval [1] 287768 0
23/06/2010
Approval date [1] 287768 0
04/08/2010
Ethics approval number [1] 287768 0
00005261

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 34537 0
Dr Tawesak Tanwandee
Address 34537 0
Division of Gastroenterology, Department of Medicine
Faculty of Medicine, Siriraj Hospital, Mahidol University,
2 Prannok Road, Bangkoknoi, Bangkok 10700, Thailand
Country 34537 0
Thailand
Phone 34537 0
66-2-419-7280-3
Fax 34537 0
Email 34537 0
[email protected]
Contact person for public queries
Name 17784 0
Michelle Miller, PhD
Address 17784 0
Biotron Limited
Suite 1.09
56 Dehli Road
North Ryde NSW 2113
Country 17784 0
Australia
Phone 17784 0
+61 2 9805 0488
Fax 17784 0
+61 2 9805 0688
Email 17784 0
[email protected]
Contact person for scientific queries
Name 8712 0
Michelle Miller
Address 8712 0
Biotron Limited
Suite 1.09
56 Dehli Road
North Ryde NSW 2113
Country 8712 0
Australia
Phone 8712 0
+61 2 9805 0488
Fax 8712 0
+61 2 9805 0688
Email 8712 0
[email protected]

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