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Trial registered on ANZCTR


Registration number
ACTRN12613001296729
Ethics application status
Approved
Date submitted
21/11/2013
Date registered
21/11/2013
Date last updated
4/07/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the safety of 3 months treatment with BIT225, in combination with pegylated interferon and ribavirin, in patients with chronic hepatitis C infection, compared to pegylated interferon and ribavirin alone, including measurement of the concentration of BIT225 in the blood and antiviral activity.
Scientific title
A Phase II, Multi-Centre, Placebo-Controlled, Randomised Study of the Safety, Pharmacokinetics and Antiviral Activity of BIT225 in Combination with Pegylated Interferon alfa-2b and Ribavirin in Patients with Hepatitis C Virus Infection.
Secondary ID [1] 283624 0
BIT225-008
Universal Trial Number (UTN)
U1111-1150-4404
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C Virus Infection 290554 0
Condition category
Condition code
Infection 290952 290952 0 0
Other infectious diseases
Oral and Gastrointestinal 290953 290953 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
Arm 1-BIT225 200mg (2 x 100mg capsules) twice daily (BID), oral, from Day 1 to Week 12.
Arm 2- Placebo capsules (2) BID, oral, from Day 1 to Week 12.
All study participants will also receive pegylated interferon alfa-2b (PEG-IFN) 80-120mcg/week by subcutaneous injection (weight based dosing) and ribavirin (RBV) 400-600mg BID, oral (weight based dosing). Hepatitis C virus (HCV) genotype 1 patients will receive PEG-IFN/RBV from Day 1 for 48 weeks, and HCV genotype 3 patients will receive PEG-IFN/RBV from Day 1 for 24 weeks, as per standard treatment guidelines.
Capsule counts on returns will be used to monitor adherence. Dosing will be observed at each study visit.
Intervention code [1] 288319 0
Treatment: Drugs
Comparator / control treatment
Placebo control. 2 capsules BID, oral, from Day 1 to Week 12.
All study participants will also receive PEG-IFN 80-120mcg/week by subcutaneous injection (weight based dosing), and RBV 400-600mg BID , oral (weight based dosing).
Hepatitis C virus (HCV) genotype 1 patients will receive PEG-IFN/RBV for 48 weeks, and HCV genotype 3 patients will receive PEG-IFN/RBV for 24 weeks, as per standard treatment guidelines.
Control group
Placebo

Outcomes
Primary outcome [1] 290935 0
To evaluate the safety and tolerability of 200 mg BIT225 BID, compared with placebo, in combination with PEG-IFN and RBV for 12 consecutive weeks in patients with genotype 1 or genotype 3 chronic HCV infection, that are treatment naive to antiviral treatment with RBV and/or Interferon (IFN). Safety and tolerability will be assessed by comparison to placebo of treatment emergent untoward medical changes, e.g. nausea, vomiting, headache, and changes in clinical laboratory assessments, vital signs and ECG measures.
Timepoint [1] 290935 0
Medical changes, vital signs and ECG measures will be evaluated on Days 2, 5, 7, 10, 14 and then weekly to Week 12. Laboratory changes will be evaluated Weeks 1, 3, 5, 7, 10, and 12.
Secondary outcome [1] 305624 0
To evaluate the antiviral activity of 200 mg BIT225 BID for 12 consecutive weeks in combination with PEG-IFN and RBV in patients with chronic HCV infection that are treatment-naive to antiviral treatment with RBV and/or IFN.
Timepoint [1] 305624 0
Blood samples for HCV RNA assays will be collected at Screening, Days 1, 2, 5, 7, 10, and 14, Weeks 3, 5, 7, 10, 12, plus in follow-up at Weeks 16, 24, 36, 48 60 and 72. HCV viral load will be determined by the Cobas Ampliprep/COBAS TaqMan HCV Test (Roche Diagnostics).
Secondary outcome [2] 305625 0
To evaluate the pharmacokinetics (PK) of 200 mg BIT225 BID administered for 12 consecutive weeks in combination with PEG-IFN and RBV in patients with chronic HCV infection.
Timepoint [2] 305625 0
A sub-group of 15 participants will participate in the intensive PK sub-study. PK samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, and 96 hours post dose Day 1 and Week 12 (Day 84).
PK samples will also be collected from all participants pre-dose on Days 2, 7, and Weeks 2, 3, 4, 5, 7, 10 and 12. These samples will be used to determine the trough plasma concentration of BIT225, as well as tracking compliance to dosing.
The concentration of BIT225 in the plasma will be measured using a validated liquid chromatography tandem mass spectrometry method.

Eligibility
Key inclusion criteria
1. Males or females aged 18 to 65 years.
2. Chronic hepatitis C infection (HCV RNA in the blood at least 6 months from initial detection).
3. Positive anti-HCV antibody test.
4. HCV genotype 1 or 3
5. HCV RNA of >/= 10^5 IU/mL within 60 days of Entry.
6. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) less than or equal to 10 times ULN (upper level of normal) within 60 days of Day 1.
7. Females of reproductive potential must have a negative serum or urine pregnancy test within 24 hours of Day 1.
8. Not to participate in a conception process. If participating in sexual activity that could lead to pregnancy, the participant must agree to use two reliable methods of contraception simultaneously while receiving study treatment and for 6 months after stopping study treatment.
9. Participants who are not of reproductive potential are eligible without requiring the use of contraceptives.
10. Provide written informed consent to participate in the study and be willing to comply with the study procedures.
11. Naive to therapy for HCV, including any IFN or RBV.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Received an investigational drug, immunomodulator, systemic cytotoxic chemotherapy, or other investigational therapy within 30 days prior to Day 1.
2. Positive results for Hepatitis B and/or HIV antibody at Screening.
3. History or presence of other evidence of a medical condition associated with chronic liver disease.
4. Bridging cirrhosis or cirrhosis confirmed on a liver biopsy, or ultrasound and fibroscan, obtained within the past 36 months as judged by a local pathologist.
5. History or signs of decompensated liver disease.
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/mm^3
b. Haemoglobin <12 g/dL in females or 13 g/dL in males
c. Platelet count <150,000/mm^3
d. International normalized ratio (INR) >1.5
e. Total bilirubin > 1.5 times the normal reference range
f. Creatinine > 1.5 mg/dL
Estimated creatinine clearance < 60 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 excluded concomitant medication (prescribed, over-the-counter or complementary) at the time of the Screening visit.
11. Active drug or alcohol use or dependence that, in the opinion of the site Investigator, would interfere with adherence to study requirements.
12. A positive result on urine screen for drugs of abuse at Screening or Day 1.
13. History of severe psychiatric disease, or depression which in the opinion of the Investigator could be exacerbated by IFN therapy. Uncontrolled or active depression or other psychiatric disorder such as untreated Grade 3 or higher psychiatric disorder, Grade 3 or higher 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 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.
20. Evidence of an active or suspected cancer or a history of malignancy within 2 years of the study.
21. 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.
22. Active thyroid disease.
23. Any patient with a baseline increased risk for anaemia or for whom anaemia would be medically problematic.
24. History or other evidence of severe retinopathy.
25. Serious illness requiring systemic treatment and/or hospitalization until the participant either completes therapy or is clinically stable on therapy, in the opinion of the site Investigator, or at least 7 days prior to study entry.
26. Known allergy/sensitivity or any hypersensitivity to components of study drug or its formulation.
27. Unable to refrain from smoking during the PK evaluation periods of the trial, if enrolled in the PK sub-study.
28. Difficulty abstaining from grapefruit, starfruit, and pomelo including, products containing these fruit, from 7 days prior to the first dose of investigational product until the end of the dosing period.
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)
Participants will be assigned to a sequentially numbered treatment in accordance with the randomisation schedule, following confirmation of eligibility. Each site will contact the central registration centre for randomisation. The centre will send the randomised medication with a matching sealed, opaque envelope to the site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation.
Stratification based on HCV genotype 1 or 3.
30 patients per genotype.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Randomisation will be 2 active to 1 placebo in each stratum.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5648 0
Thailand
State/province [1] 5648 0

Funding & Sponsors
Funding source category [1] 288309 0
Commercial sector/Industry
Name [1] 288309 0
Biotron Limited
Address [1] 288309 0
Suite 1.9
56 Delhi Road
North Ryde NSW 2113
Country [1] 288309 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Biotron Limited
Address
Suite 1.9
56 Delhi Road
North Ryde NSW 2113
Country
Australia
Secondary sponsor category [1] 287027 0
None
Name [1] 287027 0
Address [1] 287027 0
Country [1] 287027 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290203 0
Siriraj Institutional Review Board, Faculty of Medicine, Mahidol University
Ethics committee address [1] 290203 0
2 Prannok Road
Bangkoknoi
Bangkok 10700
Ethics committee country [1] 290203 0
Thailand
Date submitted for ethics approval [1] 290203 0
Approval date [1] 290203 0
12/11/2013
Ethics approval number [1] 290203 0
00005261

Summary
Brief summary
BIT225, in powder formulation, has been shown to be generally well tolerated over 28 days of dosing, when given in combination with PEG-IFN and RBV. BIT225 was effective in reducing viral load in HCV genotypes 1a and 1b. A new capsule formulation has been developed. This trial will extend the examination of BIT225, in capsule formulation, to include a longer duration of BIT225 treatment for HCV genotype 1, and includes HCV genotype 3 patients, as there is an unmet need in the population.
Trial website
Trial related presentations / publications
N/A
Public notes

Contacts
Principal investigator
Name 44446 0
A/Prof Dr Tawesak Tanwandee
Address 44446 0
Division of Gastroenterology, Department of Medicine, Faculty of Medicine
Siriraj Hospital, Mahidol University
Bangkok 10700, Thailand
Country 44446 0
Thailand
Phone 44446 0
+66-2-419-728-3
Fax 44446 0
+66-2-411-5013
Email 44446 0
tawesak@gmail.com
Contact person for public queries
Name 44447 0
Dr Michelle Miller
Address 44447 0
Biotron Limited
Suite 1.9, 56 Delhi Rd
North Ryde NSW 2113
Australia
Country 44447 0
Australia
Phone 44447 0
+61 2 9805 0488
Fax 44447 0
+61 2 9805 0688
Email 44447 0
mmiller@biotron.com.au
Contact person for scientific queries
Name 44448 0
Dr Michelle Miller
Address 44448 0
Biotron Limited
Suite 1.9, 56 Delhi Rd
North Ryde NSW 2113
Australia
Country 44448 0
Australia
Phone 44448 0
+61 2 9805 0488
Fax 44448 0
+61 2 9805 0688
Email 44448 0
mmiller@biotron.com.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary