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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01949168




Registration number
NCT01949168
Ethics application status
Date submitted
4/09/2013
Date registered
24/09/2013
Date last updated
24/09/2013

Titles & IDs
Public title
A Pilot Study of Boceprevir for the Treatment of Genotype 6 HCV
Scientific title
Phase 2a Study of Boceprevir for the Treatment of Genotype 6 Hepatitis C
Secondary ID [1] 0 0
HCV-6 study
Universal Trial Number (UTN)
Trial acronym
HCV-6
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis C 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 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
Active comparator: Boceprevir triple therapy with 5-day lead in - Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets) for 5 days, followed by boceprevir plus • Peg-Intron® (peginterferon-a-2b), 1.5ug/kg sc injection plus • Rebetol® (ribavirin), 1000/1200mg, by mouth daily for 24 weeks. In patients who achieve an undetectable plasma HCV RNA level at week 4 of triple therapy (week 5 from baseline), and maintain an undetectable plasma HCV RNA at week 20 of triple therapy (week 21 from baseline), treatment will stop at week 25. Patients who have a detectable plasma HCV RNA at week 4 of triple therapy, but an undetectable plasma HCV RNA at week 20, will continue a with follow-on peginterferon-a-2b plus ribavirin for a further 23 weeks (stopping at week 48).

Active comparator: Boceprevir triple therapy - Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets) plus Peg-Intron® (peginterferon-a-2b), 1.5ug/kg sc injection and Rebetol® (ribavirin), 1000/1200mg, by mouth daily for 24 weeks. In patients who achieve an undetectable plasma HCV RNA level at week 4 of triple therapy, and maintain an undetectable plasma HCV RNA at week 20 of triple therapy, treatment will stop at week 24. Patients who have a detectable plasma HCV RNA at week 4 of triple therapy, but an undetectable plasma HCV RNA at week 20, will continue a with follow-on peginterferon-a-2b plus ribavirin for a further 24 weeks (stopping at week 48).

Active comparator: Standard of Care - 48 weeks of Peg-Intron® (peginterferon-a-2b), 1.5ug/kg sc injection and Rebetol® (ribavirin), 1000/1200mg by mouth daily (200mg tablets)
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Early viral kinetics
Timepoint [1] 0 0
Day 5
Secondary outcome [1] 0 0
Rates of virological response
Timepoint [1] 0 0
Day 3, 5, week 2, week 4, week 12 and end of treatment (week 24 or week 48)
Secondary outcome [2] 0 0
Number of patients eligible for Response Guided Therapy
Timepoint [2] 0 0
Week 4 and week 20
Secondary outcome [3] 0 0
Rates of virological breakthrough
Timepoint [3] 0 0
Week 4, week 20, week 24, week 48, week 60
Secondary outcome [4] 0 0
Rates of SVR12 and relapse
Timepoint [4] 0 0
Week 48 and Week 60
Secondary outcome [5] 0 0
Rates of anaemia on treatment
Timepoint [5] 0 0
Day 0, 1, 2, 3, 4, 5, then monthly up to week 48 of treatment

Eligibility
Key inclusion criteria
* Male or female, at least 18 years of age
* Asian background
* HCV treatment-naïve.
* Chronic HCV infection is defined as one of the following:
* Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before Screening, and positive for HCV RNA and anti-HCVAb at the time of Screening; or
* Positive for anti-HCV Ab and HCV RNA at the time of Screening with a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment with evidence of chronic hepatitis C disease).
* Screening laboratory result indicating HCV genotype 6-infection (HCV-6).
* Plasma HCV RNA level > 10,000 IU/mL at Screening.
* IL28B C/C genotype (rs12979860)
* Per local standard practice, documented results of one of the following:
* A liver biopsy within 24 months prior to or during screening demonstrating the absence of cirrhosis, e.g., a METAVIR Score of 3 or less, Ishak score of 4 or less; or
* A screening FibroTest score of = 0.72 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) = 2; or
* A screening FibroScan result of < 9.6 kPa.
* Subjects with a non-qualifying Fibrotest/APRI or Fibroscan result may only be enrolled if they have a qualifying liver biopsy preformed within 24 months prior to or during screening.
* Candidate for PEG/RBV therapy
* Body mass index (BMI) between 18 and 36 kg/m2
* Agree to use two highly effective methods of avoiding contraception for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline
* Provide written informed consent to participate in the study.
* Subjects must have the following laboratory parameters at Screening:
* ALT = 10 × the upper limit of normal (ULN)
* AST = 10 × ULN
* Hemoglobin = 12 g/dL
* White blood cell count = 2,500 cells/µL
* Absolute neutrophil count (ANC) = 1,500 cells/mm3
* Platelets = 90,000/mm3
* Prothrombin time = 1.5 × ULN
* Albumin > 3 g/dL
* Direct (conjugated) bilirubin < ULN
* Thyroid stimulating hormone (TSH) = ULN
* Creatinine clearance (CLcr) = 50 mL/min, as calculated by the Cockcroft-Gault equation
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Non-genotype 6 HCV infection, or evidence of mixed genotype HCV infection
* IL28B C/T or T/T polymorphism (rs12979860)
* Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4.
* Exceed defined thresholds for key laboratory parameters at Screening.
* Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug.
* Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human immunodeficiency virus antibody (HIV Ab).
* Diagnosis of autoimmune disease, decompensated liver, disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed
* Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study.
* Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment, as defined by the product label.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [3] 0 0
St Vincent's Hospital - Fitzroy
Recruitment hospital [4] 0 0
Western Hospital - Footscray
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3011 - Footscray

Funding & Sponsors
Primary sponsor type
Other
Name
St Vincent's Hospital Melbourne
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the antiviral efficacy of Boceprevir-based therapy for the treatment of genotype 6 chronic hepatitis C infection.

Boceprevir has recently been approved for the treatment of genotype 1 chronic hepatitis C infection. Recent in vitro studies suggest similar efficacy against genotype 6 chronic hepatitis C infection.

The investigators therefore hypothesise that:

i) Boceprevir is a potent inhibitor of genotype 6 hepatitis C replication in vivo.

ii) Boceprevir in combination with pegylated interferon-alpha and ribavirin for 24 weeks will cure a high proportion of patients chronically infected with genotype 6 chronic hepatitis C infection.
Trial website
https://clinicaltrials.gov/study/NCT01949168
Trial related presentations / publications
Sievert W, Altraif I, Razavi HA, Abdo A, Ahmed EA, Alomair A, Amarapurkar D, Chen CH, Dou X, El Khayat H, Elshazly M, Esmat G, Guan R, Han KH, Koike K, Largen A, McCaughan G, Mogawer S, Monis A, Nawaz A, Piratvisuth T, Sanai FM, Sharara AI, Sibbel S, Sood A, Suh DJ, Wallace C, Young K, Negro F. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int. 2011 Jul;31 Suppl 2:61-80. doi: 10.1111/j.1478-3231.2011.02540.x.
Dev AT, McCaw R, Sundararajan V, Bowden S, Sievert W. Southeast Asian patients with chronic hepatitis C: the impact of novel genotypes and race on treatment outcome. Hepatology. 2002 Nov;36(5):1259-65. doi: 10.1053/jhep.2002.36781.
Ghany MG, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009 Apr;49(4):1335-74. doi: 10.1002/hep.22759. No abstract available.
Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, Sulkowski MS, Jacobson IM, Reddy KR, Goodman ZD, Boparai N, DiNubile MJ, Sniukiene V, Brass CA, Albrecht JK, Bronowicki JP; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011 Mar 31;364(13):1195-206. doi: 10.1056/NEJMoa1010494.
Bathgate A. Boceprevir for previously treated chronic hepatitis C virus genotype 1 infection. J R Coll Physicians Edinb. 2011 Jun;41(2):122-3. doi: 10.4997/JRCPE.2011.222. No abstract available.
Silva MO, Treitel M, Graham DJ, Curry S, Frontera MJ, McMonagle P, Gupta S, Hughes E, Chase R, Lahser F, Barnard RJ, Howe AY, Howe JA. Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3. J Hepatol. 2013 Jul;59(1):31-7. doi: 10.1016/j.jhep.2013.02.018. Epub 2013 Feb 27.
Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009 Sep 17;461(7262):399-401. doi: 10.1038/nature08309. Epub 2009 Aug 16.
Public notes

Contacts
Principal investigator
Name 0 0
Alexander Thompson, MBBS
Address 0 0
St Vincent's Hospital Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01949168