The primary objectives of this study are to evaluate the safety of 12 weeks of treatment with ABT-450/r/ABT-267 and ABT-333 with and without RBV, and to show the non-inferiority in SVR12 rates (the percentage of subjects achieving a 12-week…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficay:
- SVR12: non-inferiority of Arm 2 to the historical rate for telaprevir plus
pegIFN/RBV
- SVR12: non-inferiority of Arm 1 to the historical rate for telaprevir plus
pegIFN/RBV
Safety:
Safety and tolerability will be assessed by monitoring adverse events, physical
examinations, clinical laboratory tests, 12-lead ECGs and vital signs.
Secondary outcome
The secondary efficacy endpoints:
- Comparison of the percentage of subjects with a decrease in hemoglobin to
below the lower limit of normal (LLN) at the end of treatment with
ABT-450/r/ABT-267 and ABT-333 with RBV vs. without RBV;
- SVR12: Superiority of Arm 1 to the historical rate for telaprevir plus pegIFN
and RBV
- SVR12: Superiority of Arm 2 to the historical rate for telaprevir plus pegIFN
and RBV
- SVR12: Non-inferiority of Arm 2 to Arm 1
Background summary
Hepatitis C viral (HCV) infection is a global health problem, with over 170
million individuals chronically infected worldwide. While therapy for this
condition has improved considerably with approval of the protease inhibitors
telaprevir and boceprevir, these direct-acting antiviral agents (DAA) must be
used in combination with pegylated interferon (pegIFN) and ribavirin (RBV) for
up to 48 weeks. Both pegIFN and RBV are associated with considerable, often
treatment-limiting toxicity. Thus, the currently available treatment regimens
are not optimal and there is a clear unmet need for effective anti-HCV
compounds which can increase the likelihood of successful treatment and/or
decrease the need for pegIFN and RBV as components of HCV therapy.
AbbVie currently has a number of DAA compounds in clinical development:
ABT-267 is a novel NS5A inhibitor, ABT 450 is a nonstructural protein
3/nonstructural protein 4A (NS3/4A) protease inhibitor and ABT-333 is a
non-nucleoside nonstructural protein 5B (NS5B) polymerase inhibitor.
This study will explore the antiviral activity, pharmacokinetics, safety and
tolerability of combination therapy of ABT-450/r/ABT-267, ABT-333 with and
without RBV in the absence of pegIFN in pegIFN/RBV treatment-experienced, HCV
genotype 1b-infected subjects.
If a treatment arm or subgenotype of a treatment arm is terminated from further
enrollment, those subjects currently enrolled and active in the Treatment
Period will be offered either the option to continue their assigned DAA regimen
or the option to add on a 48 week course of pegIFN and RBV therapy.
Study objective
The primary objectives of this study are to evaluate the safety of 12 weeks of
treatment with ABT-450/r/ABT-267 and ABT-333 with and without RBV, and to show
the non-inferiority in SVR12 rates (the percentage of subjects achieving a
12-week sustained virologic response, SVR12, [HCV RNA < LLOQ 12 weeks following
therapy]) of both arms to the historical SVR rate of telaprevir plus pegIFN and
RBV.
The secondary objectives of this study are:
- To compare the percentage of subjects with a decrease in hemoglobin to below
the lower limit of normal (LLN) by the end of treatment with ABT-450/r/ABT-267
and ABT-333 with RBV and without RBV;
- To show the superiority in SVR12 rates of 12 weeks of treatment with
ABT-450/r/ABT-267 and ABT-333 with and without RBV to the historical SVR rate
of telaprevir plus pegIFN and RBV therapy;
- To show the non-inferiority in SVR12 rates of 12 weeks of treatment with
ABT-450/r/ABT-267, and ABT-333 without RBV (3 DAA/12) to 12 weeks of treatment
with ABT-450/r/ABT-267 and ABT-333 with RBV (3 DAA/RBV/12);
- To summarize the percentage of subjects with virologic failure during
treatment and the percentage of subjects with relapse post-treatment in each of
the treatment groups.
Study design
This is a Phase 3, open-label, randomized, combination treatment study of
ABT-450/r/ABT-267, and ABT-333 with or without RBV enrolling up to 210
pegIFN/RBV treatment-experienced, HCV genotype 1b-infected subjects at
approximately 45 sites globally .
Intervention
The study will include a screening period of up to 35 days, a treatment period
12 weeks and a 48-week follow-up period. All subjects receive study medication.
Subjects in arm 1 also receive ribavirin.
Subjects have the possibility to add pegIFN (arm 1) and pegIFN and RBV (arm 2)
for a maximum treatment period of 48 weeks. This is followed by a follow-up
period of 48 weeks.
Study burden and risks
The risks associated with this study are linked together with the possible side
effects of the investigational products, ribavirin and pegIFN.
The burden for the subject will continue to work with the study procedures,
visits and venapunctions. All subjects will be closely monitored and supervised
by experienced physicians and study staff for possible side effects.
Wegalaan 9
Hoofddorp 2132 JD
NL
Wegalaan 9
Hoofddorp 2132 JD
NL
Listed location countries
Age
Inclusion criteria
1. Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
2. Subject must have documentation that they were adherent to prior pegIFN/RBV combination
therapy and meet one of the following categories:
* Null-responders: received at least 12 weeks of pegIFN/RBV for the treatment of HCV and failed to achieve a 2 log10 reduction in HCV RNA at Week 12. Subjects will be considered to meet this definition if the lack of treatment response was documented following 10 to 16 weeks of treatment;
* Non-responders/partial responders: received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved * 2 log10 reduction in HCV RNA at Week 12, but failed to achieve HCV RNA undetectable at the end of treatment. Subjects will be considered to meet this definition if the lack of treatment response was documented following 10 to 16 weeks of treatment; or
* Relapsers: received at least 36 weeks of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 52 weeks of treatment follow-up.
Viral loads documenting the type of prior non-response should be obtained during the previous
pegIFN/RBV treatment. PegIFN/RBV therapy must have been completed no less than 2 months
prior to the Screening Visit.
3. Body mass index (BMI) is * 18 to < 38 kg/m2. Body mass index is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
4. Chronic HCV genotype 1b-infection for at least 6 months prior to study Screening. Chronic HCV infection is defined as one of the following:
* Positive for anti-HCV antibody or HCV RNA at least 6 months before Screening, and positive for HCV RNA and anti-HCV antibody at the time of Screening; or
* Positive for anti-HCV antibody and HCV RNA at the time of Screening with a liver biopsy consistent with chronic HCV infection.
5. Subject has a plasma HCV RNA level > 10,000 International Units (IU)/mL at Screening.
6. Subject's HCV genotype is subgenotype 1b at Screening without co-infection with any other
genotype/subgenotype.
Exclusion criteria
1. History of severe, life-threatening sensitivity to any drug.
2. Females who are pregnant or plan to become pregnant, or breastfeeding or males whose partner(s) are pregnant or planning to become pregnant within 6 months (or 7 months if required by the local ribavirin label) after their last dose of study drug/RBV.
3. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that, in the opinion of the investigator, could preclude adherence to the protocol.
4. Positive test result for hepatitis B surface antigen (HBsAg) or anti-HIV antibodies (anti-HIV Ab).
5. Any current or past clinical evidence of ascites or esophageal varices or prior biopsy showing cirrhosis e.g., a Metavir Score of > 3 or an Ishak score > 4.
6. Any cause of liver disease other than chronic HCV infection.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005740-95-NL |
| CCMO | NL39903.018.12 |