On
March 14, Roche announced the opening of recruitment for a 1000+ patient multinational
trial to examine a new treatment strategy in patients with chronic hepatitis C
virus (HCV) infection who have certain difficult-to-treat characteristics.
Specifically,
this randomized, double-blind study will analyze the safety and efficacy of Pegasys
(pegylated interferon alfa-2a) plus Copegus (ribavirin) in patients with no
prior treatment experience who are overweight (> 85 kilograms/187 pounds),
have genotype 1 HCV, and who have a high blood level of HCV RNA (high viral load)
(>/= 400,000 IU/mL).
Overweight
individuals with high blood levels of genotype 1 HCV historically have not responded
well to standard treatment with pegylated interferon plus ribavirin. Called PROGRESS
(Pegasys and Ribavirin
Optimized in Genotype
1 high virRal load patiEntS
to improve SVR), the trial will explore the
potential for improved treatment success rates in this population using varying
higher doses of Pegasys and ribavirin.
4
Treatment Arms
The
PROGRESS trial will enroll more than 1000 patients, who will be randomly assigned
to receive 1 of 4 dosing regimens of Pegasys plus ribavirin for 48 weeks, followed
by a 24-week treatment-free follow-up period:
(1)
Fixed-dose induction of Pegasys 360 mcg given once weekly for the first 12 weeks,
followed by the standard 180 mcg dose of Pegasys for the next 36 weeks. Patients
will also receive high-dose ribavirin (1,400-1,600 mg daily) for the full 48-week
treatment period.
(2)
Fixed-dose induction of Pegasys 360 mcg given once weekly for the first 12 weeks,
then the standard 180 mcg dose of Pegasys for the following 36 weeks. Patients
will also receive a standard dose of ribavirin (1,000-1,200 mg daily) for the
full 48 weeks.
(3)
The standard 180 mcg dose of Pegasys for 48 weeks plus high-dose ribavirin (1,400-1,600
mg daily) for the full 48-week treatment period.
(4)
A control group will receive the standard of care: 180 mcg once-weekly Pegasys
plus 1,000-1,200 mg daily ribavirin for the full 48-week treatment period.
Primary
Outcome: Sustained virological response (SVR) at week 72.
Secondary
Efficacy Outcomes: SVR at 24 weeks after the end of treatment; virological
response at week 48, week 60, at the end of treatment, and 12 weeks after the
end of treatment.
•
Adult patients >/=18 years of age; •
Chronic hepatitis C infection;
•
Genotype 1 HCV;
•
HCV RNA >/= 400,000 IU/mL;
•
Baseline body weight >/=
85 kg (187 pounds);
•
Liver biopsy within 24 months
of first dose, with results consistent with chronic hepatitis C.
Exclusion
criteria:
•
Previous treatment with interferon,
ribavirin, viramidine, levovirin, or investigational HCV polymerase or protease
inhibitors;
•
Other forms of liver disease,
including liver cancer;
•
HIV infection.
Gender:
Males and females
Age limit: Minimum 18 years; no maximum limit
The
trial will include participants from 15 countries at a total of 150 trial sites.
Enrollment is currently ongoing in the U.S., and well as in Belgium, Brazil, Canada,
Denmark, Finland, France, Germany, Hungary, Norway, Poland, Romania, Russia, Sweden,
and the United Kingdom.
The trial is expected to conclude in 2008.
Title
of Study: A Study of Induction Dosing With PEGASYS (Peginterferon alfa-2a
(40KD)) Plus Copegus in Treatment-Naive Patients With Chronic Hepatitis C
The
following patient information on Pegasys and Copegus is provided by Roche: About
PEGASYS
PEGASYS,
in combination with COPEGUS (ribavirin), is indicated for the treatment of adults
with chronic hepatitis C who have compensated liver disease and have not previously
been treated with interferon alpha. Efficacy has been demonstrated in patients
with compensated liver disease and histological evidence of cirrhosis (Child-Pugh
class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral
therapy not required or receiving stable antiretroviral therapy).
In
addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved
regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis
C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment
of adult patients with chronic hepatitis B (HBeAg positive and HbeAg negative
chronic hepatitis B who have compensated liver disease and evidence of viral replication
and liver inflammation).
PEGASYS
is dosed at 180 mcg as a subcutaneous injection taken once a week. COPEGUS is
available as a 200mg tablet, and is administered orally two times a day as a split
dose. Roche has backed PEGASYS with the most extensive clinical research program
ever undertaken in hepatitis C, with major studies initiated to advance treatment
for hepatitis C patients with unmet needs, including patients co-infected with
HIV and HCV, African Americans, patients with cirrhosis, and patients who have
failed to respond to previous therapy.
Important
Safety Information about PEGASYS
What
is PEGASYS?
PEGASYS
is a medicine used to treat some adults who have hepatitis C or hepatitis B and
signs of liver damage. PEGASYS works to reduce the amount of virus in your blood,
helping your body fight the virus.
PEGASYS
(Peginterferon alfa-2a), like other alpha interferons, can cause fatal or make
life-threatening problems worse (like mental, immune system, heart, liver, lung,
intestinal and infections). Your doctor should monitor you during regular visits.
If you show signs or symptoms of these conditions, your doctor may stop your medication.
In most patients, these conditions get better after you stop taking PEGASYS (see
medication guide for more information and warnings).
What
is COPEGUS?
COPEGUS
is a medicine that works by slowing down the growth of the virus. COPEGUS should
be taken with PEGASYS to fight the virus. Do not take COPEGUS by itself. COPEGUS
(Ribavirin, USP) can be extremely harmful and cause birth defects in an unborn
baby. Female patients and the female partners of male patients should avoid getting
pregnant. Ribavirin is known to cause anemia (low red blood cells), which can
make heart disease worse. Also, Ribavirin can harm your DNA and possibly cause
cancer (see medication guide for more information and warnings).
Who
should not take PEGASYS and COPEGUS?
Do
not take PEGASYS alone or with COPEGUS if:
•
You are pregnant or your partner is pregnant
•
You or your partner
plans to get pregnant during therapy or within 6 months after treatment ends
•
You are breastfeeding
•
You have hepatitis
caused by your immune system (autoimmune hepatitis)
•
You have unstable or
severe liver disease before or during treatment
•
You are allergic to
alpha interferons or any of the ingredients in PEGASYS and COPEGUS
•
You have abnormal red
blood cells (caused by conditions like sickle-cell anemia or thalassemia major)
What
if I am pregnant or thinking about having a baby?
If
you are a woman who could get pregnant, you must take pregnancy tests before,
during, and for 6 months after treatment ends to make sure you are not pregnant.
During treatment and for 6 months after treatment, female and male patients must:
•
Use 2 forms of birth
control (one being a condom with spermicide)
•
Tell your doctor right
away if you or your partner becomes pregnant. You or your doctor should also call
the Ribavirin Pregnancy Registry at 1-800-593-2214
What
medication should I avoid when I am taking PEGASYS and COPEGUS?
You
should not take didanosine [ddI; Videx] with COPEGUS. Talk to your doctor about
all medications that you are taking.
What
are the possible side effects?
The
most common side effects of PEGASYS and COPEGUS are:
•
Skin problems (like
rash, dry or itchy skin, redness and swelling at injection site)
•
Hair loss (temporary)
•
Trouble sleeping.
The
most serious side effects of PEGASYS and COPEGUS are:
•
Risks to pregnancies
•
Mental health problems
(such as irritability, depression, anxiety, aggressiveness, trouble with drug
addiction or overdose, thoughts about suicide, suicide attempts, suicide and thoughts
about homicide)
•
Blood problems (like
a drop in blood cells leading to increased risk for infections, bleeding and/or
heart or circulatory problems)
•
Liver problems (rarely,
liver function worsens). Patients with both the hepatitis C virus and HIV can
have an increased chance of having liver failure during PEGASYS treatment.
Change
in a blood test that measures liver inflammation occurs more often in patients
with hepatitis B. If you have a rise in this blood test you may need to be watched
more closely with additional blood tests.
Tell
your doctor immediately if you think you or your partner may be pregnant or if
any of these symptoms occur.
03/16/07
Sources
Roche.
Roche Driving PROGRESS in Treatment of Hepatitis C Patients with New Pegasys Trial.
Press Release. March 14, 2007.
