The primary objective of this study is to evaluate the efficacy of SCH 503034800 mg TID PO in combination with PegIntron 1.5 *g/kg QW SC plus ribavirin (800 - 1400 mg/day) in previously untreated adult chronic hepatitis C (CHC) subjects infected…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint: The primary efficacy endpoint is the achievement of
SVR, defined as plasma HCVRNA levels below the lower limit of detection at
follow-up week 24 (FW 24). Subjects will be declared treatment failures in one
of the following ways:
* Subjects in any of the 5 treatment arms who are HCV-RNA positive at FW 24.
* Subjects in any of the 5 treatment arms who are missing their HCV-RNA level
at FW 24 and are not HCV-RNA negative at FW 12.
Secondary outcome
Key Secondary Efficacy Endpoint(s): The secondary endpoints in this study are:
* The proportion of subjects with HCV-RNA levels below the limit of detection
at FW 12.
* The proportion of subjects with HCV-RNA levels below the limit of detection
at 72 weeks post randomization.
* The relationship between early virologic response (EVR) and SVR.
* The relationship between virologic response at FW 12, FW 24 (SVR), and 72
weeks post randomization.
Background summary
Combination therapy with peginterferon and weight-based ribavirin is the
standard of care for the treatment of chronic hepatitis C patients infected
with HCV genotype 1; however, only approximately 50% of these patients achieve
sustained virologic response (SVR). SCH 503034 blocks the HCV NS3 protease,
thereby preventing viral replication, a new mechanism of action compared to
both interferon alfa and ribavirin. SCH 503034 may improve virologic response
and shorten treatment duration when added to the current standard of care
regimen of peginterferon alfa-2b plus ribavirin.
Study objective
The primary objective of this study is to evaluate the efficacy of SCH 503034
800 mg TID PO in combination with PegIntron 1.5 *g/kg QW SC plus ribavirin (800
- 1400 mg/day) in previously untreated adult chronic hepatitis C (CHC) subjects
infected with genotype 1.
Secondary Objectives
The secondary objectives of this study are as follows:
* To evaluate the safety of SCH 503034 when used in combination with
PegIntron 1.5 *g/kg QW SC plus ribavirin (800 to 1400 mg/day PO).
* To assess the relationship of early virologic response (EVR) and time to
HCV-RNA negative, to SVR.
* To assess the effect of the 4 week lead in with PegIntron and
ribavirin on SVR (FW 24).
* To assess the effect of duration of treatment with SCH 503034 on
SVR.
* To assess the proportion of subjects with HCV-RNA levels below the
limit of detection at FW 12.
* To assess the proportion of subjects with HCV-RNA levels below the
limit of detection at 72 weeks post randomization.
* To explore the relationship between virologic response at FW 12, FW
24 (SVR), and 72 weeks post randomization.
Study design
Randomized, 5-arm, comparative, open-label trial to be conducted in conformance
with Good Clinical Practice. The 5 arms of the study will compare: PegIntron
and ribavirin for 4 weeks followed by PegIntron, ribavirin and SCH 503034 for
44 weeks (Arm 5) versus PegIntron, ribavirin and SCH 503034 for 48 weeks (Arm
4) versus PegIntron and ribavirin for 4 weeks followed by PegIntron, ribavirin
and SCH 503034 for 24 weeks (Arm 3) versus PegIntron, ribavirin, and SCH 503034
for 28 weeks (Arm 2) versus PegIntron and ribavirin for 48 weeks (control, Arm
1).
Type of Blinding: Open-label.
Randomization: 1:1:1:1:1
Stratification: Black vs non-Black and cirrhosis vs no cirrhosis.
Intervention
The 5 arms of the study will compare: PegIntron and ribavirin for 4 weeks
followed by PegIntron, ribavirin and SCH 503034 for 44 weeks (Arm 5) versus
PegIntron, ribavirin and SCH 503034 for 48 weeks (Arm 4) versus PegIntron and
ribavirin for 4 weeks followed by PegIntron, ribavirin and SCH 503034 for 24
weeks (Arm 3) versus PegIntron, ribavirin, and SCH 503034 for 28 weeks (Arm 2)
versus PegIntron and ribavirin for 48 weeks (control, Arm 1).
*PegIntron by injection (under the skin) once a week. The dose of PegIntron
will be based on the weight on Day 1 of visit 1.
*Rebetol capsules twice daily with food (morning and evening). The dose of
Rebetol (800-1400 mg/day) will be based on the weight on Day 1 of visit 1.
*SCH 503034 capsules 3 times each day (optimally every 8 hours (7 to 9 hours))
with food.
Study burden and risks
Burden: # visits and Blood drawings
blood drawings: approximately 15-20 max 30 ml blood per visit.
If we take 30 ml perv isit:
Arm 1 14 visits in 48 weken (HCV neg.) and 20 visits in 48 weeks (HCV pos.);
max 520ml/48 weeks en max 600ml/48 weeks,
Arm 2 11 visits in 28 weeks; max 330ml/28 weeks
Arm 3 11 visits in 28 weeks max 330ml/28 weeks
Arm 4 14 visits in 48 weeks max 420ml/48 weeks
Arm 5 14 visits in 48 weeks max 420ml/48 weeks
Arm 1,4 en 5: 3 visits in 24 weeeks follow-up period.
Arm 2 and 3: 5 visits in 44 weeks follow up
Risk:
Research studies often involve some risks, not all of which may be currently
known. SCH 503034, PegIntron and Rebetol are associated with side effects, as
described in the protocol and patient information form.
Drawing blood may cause discomfort or bruising from the insertion of the
needle, fainting (infrequent) and infection at the needle stick site (rare).
Maarssenbroeksedijk 4
3542 DN Utrecht
Nederland
Maarssenbroeksedijk 4
3542 DN Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
1. Subject must be between 18 and 60 years of age; 2. Subject*s body weight must be between 45 and 125 kg; 3. Subject must have documented chronic hepatitis C genotype 1 with most recent (within 6 months of Day 1) quantitative HCV-RNA result greater than or equal to 10,000 IU/mL; 4. Subject must have a liver biopsy within 5 years of Day 1 with histology consistent with chronic hepatitis and no other etiology for chronic liver disease. A copy of the local pathology report must be available in the site*s file; 5. Subject and subject's partner(s) must each agree to use acceptable methods of contraception 2 weeks prior to Day 1 and at least 6 months or longer if dictated by local regulations after last dose of study drug (see Section 7.6.1). 6. Subjects must be willing to give written informed consent
Exclusion criteria
1. Subjects who received prior treatment for hepatitis C
2. Subjects known to be co-infected with HIV or hepatitis B virus (HBsAg positive)
3. Evidence of decompensated liver disease as specified in the protocol
4. Diabetic and hypertensive subjects with clinically significant ocular exam findings
5. Pre-existing psychiatric condition as specified in the protocol
6. Clinical diagnosis of substance abuse of drugs, see for details protocol.
7. Evidence of active or suspected malignancy, or a history of malignancy, within the last 5 years (except adequately treated basal cell carcinoma of the skin)
8. Subjects who are pregnant or nursing. Subjects who intend to become pregnant during the study period. Male subjects with partners who are, or intend to become, pregnant during the study period
9. Participation in any other clinical trial within 30 days of the screening visit or intention to participate in another clinical trial during participation in this study. Treatment with any investigation drug within 30 days of screening visit in this study.
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 | EUCTR2006-002543-92-NL |
| CCMO | NL14950.018.06 |