The objectives are:- to provide access to telaprevir for subjects with chronic HCV genotype 1 infection who wererandomized to the control group in the C216 trial and who failed therapy for virologicreasons;- to evaluate efficacy, safety, and…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary parameter is the proportion of subjects achieving SVR, defined as
having< 25 IU/mL undetectable plasma HCV RNA levels 24 weeks after the last
dose of study medication.
The following treatment success and treatment failure definitions will be
applied to the analysis of the primary efficacy parameter:
1.Treatment Success
The following subjects will be considered treatment successes:
* Subjects who complete treatment and achieve SVR;
* Subjects who prematurely discontinue treatment for reasons other than
virologic failure and who achieve SVR.
2.Treatment Failure
The following subjects will be considered treatment failures:
* Subjects who complete treatment and have detectable HCV RNA levels at the end
of treatment or relapse during antiviral follow-up;
* Subjects with a missing SVR assessment;*
Subjects who prematurely discontinue or change treatment based on virologic
response assessments whether or not they complete the follow-up period and
achieve SVR.
Secondary outcome
The secondary parameters related to antiviral activity are:
Proportion of subjects achieving undetectable HCV RNA levels at different time
points;
Proportion of subjects who have undetectable HCV RNA levels at the end of
treatment (i.e., Week 48 or early discontinuation of all study
medication);
Proportion of subjects who meet the telaprevir stopping rule, defined as having
HCV RNA levels > 100 IU/mL at 4 or 8 weeks after start of telaprevir;
Proportion of subjects who relapse, defined as having detectable HCV RNA levels
during the follow-up period after previous undetectable HCV RNA levels at end
of treatment (i.e., Week 48 or early discontinuation of all study medication).
Background summary
The likelihood of a patient achieving sustained virologic response (SVR;
defined as having undetectable plasma HCV RNA levels 24 weeks after the last
dose of study medication) has improved with the availability of long-acting
pegylated interferon (Peg-IFN) plus ribavirin (RBV) treatment, with SVR rates
ranging from 20 to 50% in subjects with chronic HCV genotype 111-14. Despite
the significant advances that have been made in the treatment of chronic HCV
infection in recent years, there is an ongoing need for an effective treatment
in patients who fail to achieve SVR with the currently available antiviral
therapy.
At present, the majority of patients who have received therapy for chronic
hepatitis C infection have been treated with Peg-IFN/RBV as initial therapy or
as re-treatment after a lack of response to initial therapy (defined as < 2-log
decline in HCV RNA level over the first 3 months of
therapy or failure to achieve viral negativity or relapse following completion
of treatment).
Previous trials have demonstrated that re-treatment with Peg-IFN/RBV of
subjects who have HCV genotype 1 and failed treatment with Peg-IFN/RBV results
in low response rates, especially when these subjects were non-responders to
prior treatment (defined as subjects who did not reach undetectable levels) as
opposed to relapse subjects15-19. There is an increasing number of patients who
have failed Peg-IFN and RBV therapy, either as their initial course of
treatment or as re-treatment after not achieving SVR. An estimated 232,000
people in the US
(8% of the total HCV-infected population) have HCV genotype 1 infection and
have failed previous treatment20.
In recent years, Peg-IFN alfa-2a/RBV has been approved in Europe and Peg-IFN
alfa-2b/RBV in Europe and in the US for patients who have failed previous
hepatitis C treatment21,22. No alternative treatment with proven superiority is
currently available for patients who did not
achieve SVR after treatment with Peg-IFN/RBV in many regions of the world. The
need for a successful treatment that can reduce the risk of HCV-related
complications, such as hepatocellular carcinoma and decompensated liver
disease10, is particularly urgent for non-responders. Therefore, a potent
antiviral drug such as telaprevir that could be administered in combination
with direct or indirect-acting antivirals and generate higher SVR rates is
highly desirable.
Study objective
The objectives are:
- to provide access to telaprevir for subjects with chronic HCV genotype 1
infection who were
randomized to the control group in the C216 trial and who failed therapy for
virologic
reasons;
- to evaluate efficacy, safety, and tolerability of telaprevir in combination
with
Peg-IFN alfa-2a and RBV in these subjects;
- to evaluate amino acid changes from baseline in the HCV NS3 protease domain.
Study design
This is an open-label, single-arm, roll-over trial of telaprevir in combination
with Peg-IFN alfa-2a (Pegasys) and RBV (Copegus). The purpose of this trial is
to provide access to telaprevir for subjects who were randomized to the control
group in the C216 trial and who failed
therapy for virologic reasons.
The efficacy, safety, and tolerability of telaprevir in combination with
Peg-IFN alfa-2a and RBV will be evaluated. In addition, amino acid changes from
baseline in the HCV NS3 protease domain will be evaluated.
The trial will consist of a screening period of approximately 28 days, a
48-week treatment period, and a 24-week follow-up period.
All subjects will receive 12 weeks of telaprevir 750 mg q8h in combination with
Peg-IFN alfa-2a and RBV at standard doses, i.e., 180 µg once weekly and 1,000
or 1,200 mg/day (weight-based), respectively, followed by 36 weeks of Peg-IFN
alfa-2a and RBV at standard doses.
Intervention
Approximately 120 subjects will be enrolled in this trial.
A total of 130 subjects were planned to be randomized to the control group in
the C216 trial. Of
these, it is expected that approximately 120 subjects will have failed therapy
for virologic reasons in the C216 trial, will meet the in- and exclusion
criteria, and will wish to participate in the current trial.
Since all subjects receive the same treatment, randomization is not applicable.
All subjects will receive 12 weeks of telaprevir 750 mg every 8 hours (q8h) in
combination with Peg-IFN alfa-2a and RBV at standard doses, i.e., 180 µg once
weekly and 1,000 or 1,200 mg/day (weight-based), respectively, followed by 36
weeks of Peg-IFN alfa-2a and RBV at standard doses.
Subjects with hepatitis C virus RNA levels < 25 IU/mL undetectable at the end
of treatment (Week 48 or having discontinued earlier) will
be followed for 24 weeks after the last dose of study medication to assess
sustained virologic response (SVR).
Safety/tolerability assessments will be performed and adverse events (AEs),
regardless of severity, will be collected continuously until the
Safety Follow-up Visit, scheduled 4 weeks after the last dose of study
medication. Thereafter, only serious adverse events (SAEs) will be
reported.
HCV RNA quantification will be performed at regular time points throughout the
trial. Sequencing analyses of the HCV NS3 protease
domain will be performed in case of virologic failure or when a subject's HCV
RNA level becomes detectable during the follow-up
period after previous undetectable level at the end of treatment (relapse).
Additionally, upon request of the Protocol Virologist from
Tibotec, other samples may be analyzed.
Study burden and risks
The following assessments are included in this trial (also see flow chart
protocol page 8): ECG, assessment of the liver, physical examination, vital
signs, blood draws, urine tests, pregnancy tests (on blood at screening and
urine test rest of trial), fasting before visits, eye test.
Dr Paul Janssenweg 150
5026 RH Tilburg
NL
Dr Paul Janssenweg 150
5026 RH Tilburg
NL
Listed location countries
Age
Inclusion criteria
1. Subject was randomized to the control group in the C216 trial and failed therapy for virologic reasons.
2. Before entry in the current trial, all assessments in the C216 trial, including the Safety Follow up Visit, will have to be completed.
3. Subject is judged to be in good health (besides HCV infection) in the opinion of the investigatorl.
4. If heterosexually active, a female subject of childbearing potential and a non-vasectomized male subject who has a female partner of childbearing potential must agree to the use of 2 effective methods of contraception from screening onwards until 6 months (female subject) or 7 months (male subject) after the last dose of RBV.
5. Subject is willing and able to refrain from the concomitant use of any disallowed medications, substances, or foods, from 14 days prior to the first day of study medication dosing through the end of treatment.
6. Subject is able to read and understand, and is willing to sign the ICF voluntarily before first trial-related activity and abide by the trial restrictions.
7. Subjects should agree not to participate in other clinical trials for the duration of his/her participation in this trial, except for non-interventional or observational trials and after prior approval of the sponsor.
Exclusion criteria
1. Subjects who prematurely discontinued study medication in the C216 trial because of noncompliance (as deemed by the investigator) or for whom repeated treatment would be inappropriate for safety reasons.
2. Subject received any direct acting anti-viral HCV therapy after discontinuation of the C216 trial.
3. Subject has developed any new contraindication to the administration of Peg IFN alfa-2a or RBV since his/her enrollment in the C216 trial.
4. Subject has an active of pre-existing psychiatric condition that in the opinion of the investigator could interfere with the subject*s participation in and completion of the trial for safety and for other reasons.
*Subject has history of decompensated liver disease: history of ascites, hepatic encephalopathy, or bleeding esophageal varices, and/or any of the following screening laboratory results: International Normalized Ratio (INR) of * 1.5; Serum albumin < 3.3 g/dL; Serum total bilirubin > 1.8 times upper limit of laboratory normal range (ULN).
5. Subject has active malignant disease or history of malignant disease within the past 5 years.
6. Subject with cirrhosis who has hepatocellular carcinoma.
7. Subject has history of seizure disorders.
8. Subject has history of organ transplant that requires chronic immunosuppression.
9. Subject has a medical condition that requires use of systemic corticosteroids.
10. Diabetic or hypertensive subject with clinically significant ocular exam findings.
11. Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis.
12. Subject has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection.
13. Subject has a history of acute or chronic pancreatitis.
14. Suspicion exists of alcohol, barbiturate, or amphetamine recreational or narcotic drug use, current or within 2 years prior to the screening visit, that in the investigator*s opinion would compromise the subject*s safety and/or compliance with study procedures.
15. Subject or female partner is pregnant or planning to become pregnant.
16. Subject is breastfeeding.
17. Subject has any clinically significant laboratory abnormalities as judged by the investigator.
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 | EUCTR2009-012613-21-NL |
| CCMO | NL30658.091.09 |