The primary objective of this study is to evaluate the safety and antiviral efficacy, defined as the percentage of subjects with sustained virologic response 12 weeks post-dosing (SVR12; HCV RNA < LLOQ 12 weeks after the last dose of study drug).…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Efficacy:
The primary efficacy endpoint is the percentage of subjects with sustained
virologic response 12 weeks after the last actual dose of study drug (including
DAA, pegIFN, and RBV) (SVR12actual).
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 are the percentage of subjects with sustained
virologic response 24 weeks after the last actual dose of study drug (including
DAA, pegIFN, and RBV) (SVR24actual) and the percentage of subjects with eRVR
(HCV RNA < LLOQ at Weeks 4 through 12 in Substudy 1).
Background summary
Hepatitis C viral (HCV) infection is a global health problem, with over 170
million individuals infected worldwide. While therapy for this condition has
improved considerably, the currently available treatment regimens are not
optimal. Until recently, the standard of care (SOC) for treatment of HCV
genotypes 1a and 1b (the most common genotypes in North America and Europe)
consisted of weekly injections of pegylated
interferon-alpha (pegIFN) and daily oral doses of ribavirin (RBV) for up to 48
weeks. Approximately 50% of patients with genotype 1 HCV infection treated with
pegIFN and RBV fail to achieve a sustained virologic response (SVR). Thus,
there is a clear unmet need for effective anti-HCV compounds which can increase
the likelihood of successful treatment for this population.
To meet this need, a number of small molecules with direct antiviral activity
(direct-acting antiviral agent [DAA]) against specific stages of the HCV life
cycle have been developed. Clinical studies to date with these DAA HCV
inhibitors, such as the NS3/4A protease inhibitors telaprevir and boceprevir,
used in combination with pegIFN plus RBV, have demonstrated improved SVR rates
in treatment-naïve and pegIFN-experienced
patients, with shorter treatment durations for a subset of naïve subjects. As a
result, these regimens are now considered the standard of care for chronic
genotype 1 HCV infection.
Abbott/AbbVie currently has a number of DAA compounds in clinical development:
ABT-450 is an NS3/NS4A protease inhibitor and ABT-267 is an NS5A inhibitor, and
ABT-333 is a non-nucleoside NS5B polymerase inhibitor.
The current study is intended to offer subjects who experience virologic
failure in a previous pegIFN-free Abbott DAA combination study an optional
intensified treatment regimen. This study will assess the safety, antiviral
activity and resistance profile of ABT-450/r 200/100 mg QD and ABT-267 25 mg QD
combined with pegIFN and RBV in subjects who met a virologic failure criterion
in a previous study.
Study objective
The primary objective of this study is to evaluate the safety and antiviral
efficacy, defined as the percentage of subjects with sustained virologic
response 12 weeks post-dosing (SVR12; HCV RNA < LLOQ 12 weeks after the last
dose of study drug).
The secondary objectives of this study are to evaluate the percentage of
subjects with sustained virologic response 24 weeks post-dosing (SVR24; HCV RNA
< LLOQ 24 weeks after the last dose of study drug) and the percentage of
subjects with extended rapid virologic response (eRVR) (HCV RNA < LLOQ at TI
Weeks 4 through 12).
Study design
This is an open label, multiple-dose, rollover study exploring the safety,
antiviral activity and pharmacokinetics of ABT-450 with ritonavir (ABT-450/r) +
ABT-267 in combination with pegIFN and RBV in HCV-infected subjects who have
experienced virologic failure in a previous AbbVie/Abbott DAA combination
study.
Intervention
This protocol consists of three substudies. In Substudy 1, subjects who have
met virologic stopping criteria in a previous Abbott DAA combination study may
choose to enter this study and receive intensified treatment with ABT-450/r,
ABT-267, pegIFN and RBV for 24 weeks. Subjects who complete or discontinue DAA
treatment in Substudy 1 will enter Substudy 2. In Substudy 2, subjects receive
pegIFN and RBV for an additional 24 weeks for a total treatment of up to 48
weeks across Substudies 1 and 2. In Substudy 3, subjects will be monitored for
resistance and viral response for 48 weeks after discontinuation of study drug
treatment.
Study burden and risks
The risks associated with this study are linked together with the possible side
effects of the investigational products, ritonavir, ribavirin and peglFN.
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. Subject must have experienced virologic failure as defined in a previous AbbVie/Abbott DAA
combination trial.
2. Female who is:
* not of childbearing potential, defined as:
* postmenopausal for at least 2 years prior to screening (defined as amenorrheic for longer than 2 years, age appropriate, and confirmed by a follicle-stimulating hormone [FSH] level indicating a postmenopausal state), or
* surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or has a vasectomized partner(s), or
* practicing total abstinence from sexual intercourse (minimum 1 complete menstrual cycle), or
* sexually active with female partners only
* of childbearing potential and sexually active with male partner(s):
* currently using at least one effective method of birth control at the time of screening and agree to practice two effective methods of birth control while receiving study drugs (as outlined in the subject information and consent form or other subject information documents), starting with Study
Day 1 and for 7 months after stopping study drug as directed by the local ribavirin label (Note: Hormonal contraceptives, including oral, topical, injectable or implantable varieties, may not be used during Substudy 1 or for 2 weeks after the last dose of DAA therapy) study drug treatment.
3. Females must have negative results for pregnancy tests performed:
* at Screening by urine specimen within 42 days prior to initial study drug administration, and
* at Baseline (prior to dosing) by urine specimen.
Female subjects with a borderline hCG result at Day 1 may enroll into the study if they either:
* have a documented history of bilateral tubal ligation, hysterectomy, bilateral oophorectomy; or
* are confirmed to be postmenopausal defined as amenorrheic for longer than 2 years, age appropriate, and confirmed by a follicle-stimulating hormone (FSH) level indicating a postmenopausal state at Screening.
4. Sexually active males must be surgically sterile or have male partners only or if sexually active with female partner(s) of childbearing potential must agree to practice two effective forms of birth control (as outlined in the subject information and consent form or other subject information documents) throughout the course of the study, starting with Study Day 1 and for 7 months after stopping study drug or as directed by the local ribavirin label. (Note: Contraceptives containing ethinyl estradiol or depo-progesterone are considered effective if used by the female
partners of male subjects.)
5. For cirrhotic subjects, compensated cirrhosis defined as Child-Pugh score of * 6 at Screening.
6. Subject is infected with HCV genotype 1 at Screening Visit.
Exclusion criteria
1. In subjects with a prior null or partial response to pegIFN/RBV treatment at any time prior to
pre-screening for this study or any prior failure with pegIFN/RBV plus telaprevir, the presence of
variants relative to the appropriate prototypic reference sequence (H77 for 1a or Con1 for 1b) at any of the following amino acid positions: NS3 protease 155, 156, or 168; NS5A 28, 29, 30, 31, 32, 58, or 93.
2. 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 RBV.
3. Use of known strong inhibitors (e.g., ketoconazole) or inducers (e.g., phenobarbital, rifampin,
carbamazepine, St. John's Wort) of CYP3A within 2 weeks prior to study drug administration.
4. Use of any medications contraindicated for use with ABT 450, ABT 267, pegIFN, RBV or ritonavir
within 2 weeks prior to study drug administration.
5. Discontinuation of antiviral therapy due to intolerance or a DAA or RBV associated adverse event in a previous AbbVie/Abbott DAA combination study (excluding intolerance or AEs associated with telaprevir).
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 | EUCTR2011-005393-32-NL |
| ClinicalTrials.gov | NCT01609933 |
| CCMO | NL40079.018.12 |