last updated: 21 Sept 2004

KNOWN RISKS WHEN USING PEGASYS^®/COPEGUS^® for treatment/trial treatment of Hep C

(directly extracted from my USC/Hoffmann-La Roche REPEAT Trial MV 17150 'Implied Consent Form')
[extracted from pages 7 through page 10 of said document]
RISKS:

Research studies often involve some risks, not all of which may be currently know.  You will be closely monitored for any risks.

PEGASYS^® (PEG-INF alpha2a) plus COPEGUS^® (ribavirin)

The most common possible side effects of PEGASYS^® plus COPEGUS^® combination treatment (seen in 1/4 to 1/2 of the subjects in previous studies using these 2 drugs) include flu-like symptoms such as fever, chills, muscle aches, headaches, extreme fatigue (tiredness), upset stomach (including related events such as nausea, taste changes, and diarreha), redness and swelling at the site of the injection, temporary hair loss, loss of appetite, and trouble sleeping.  Other common possible side effects (seen in fewer than 1/4 of the subjects in previous studies using these 2 drugs) include joint pain, blood sugar problems which may lead to diabetes, skin reactions such as rash, dry or itchy skin, dizziness, difficulty concentrating, cough and weight loss.  Subjects who develop dizziness, confusion, sleepiness, or fatigue during treatment with PEGASYS^® plus COPEGUS^® should be cautioned to avoid driving or operating machinery.

The most serious possible side effects of treatment with PEGASYS^® plus COPEGUS^® combination therapy include risks to pregnancies, mental health problems (including irritability, depression, anxiety, agressive behavior, suicidal behavior including thoughts about suicide and suicide attempts, and trouble with drug addiction or overdose), blood problems (including a drop in various blood cells which can lead to an increased risk for infections, bleeding, and/or heart or circulatory problems), infections (which have sometimes caused death)), lung problems (including trouble breathing and pneumonia), eye problems (including blurred vision or loss of vision), autoimmune problems (where the body's own immune system attacks itself including psoriasis and thyroid problems), and heart problems (including chest pain and, rarely, a heart attack).

Most side effects (with the possible exception of altered thyroid function) will generally reverse upon stopping treatment.

Since PEGASYS^® is given by injection under the skin, you may have pain, redness or swelling at the injection site.

Blood Drawing:  Blood drawing is mildly painful and can cause bruising and, very rarely, fainting, blood clots on an infection at the site.

Liver Biopsy:  A liver biopsy may require a six-hour stay in teh hospital.  The procedure includes numbing the skin over the liver with a local anesthetic, followed by passing a small needle into the liver and removing a small core of liver tissue.  There is some discomfort associated with the procedure.  The discomfort should not last more than several hours.  The risks include bleeding from the biopsy site, significant bleeding requiring a blood transfusion or surgery to control the bleeding (less than 1/10,000 subjects), perforation of internal organs (less than 1/1,000 subjects) and death (less than 1/10,000 subjects).  You may be asked to sign a separate consent for this procedure.

Unknown Risks:  Complications and side effects that are unknown at this time could occur.

Randomization:  The way you take your medicine listed above may later be shown to be less effective for your hepatitis condition, or to have more risks or side effects than the treatment plan assigned to other subjects participating in this study.

PREGNANCY STATEMENT:

Treatment with interferons may present  risks to an embryo or fetus (an unborn baby).  Copegus^® (ribavirin) may produce birth defects.  BOTH fertile women and men must practice TWO medically effective forms of birth control while taking COPEGUS^®.

COPEGUS^® (ribavirin), which can concentrate in the semen, has the potential to cause birth defects in an unborn baby.  If you are male and have unprotected sexual intercourse with your partner, you may expose your unborn baby to COPEGUS^®.  This exposure can cause abnormalities of the central nervous system (brain and spinal cord) (seen more with exposure to ribavirin during the early months of pregnancy), abnormal bones (seen more with exposure to ribavirin in the later stages of pregnancy), abnormal muscles, and abnormal eyes.  COPEGUS^® has also been shown to be associated with a higher rate of death of both born and unborn babies.

The rate of severity of the birth defects seen with ribavirin increases with increasing exposure to ribavirin.

Both men and women will be included in this study.  All subjects must use TWO reliable forms of effective birth control methods (at the same time) of their choice [example: barrier method (condoms, diaphragm; oral, injecgable, or implant birth control; or abstinence].  Women of childbearing potential should not take the study medicines unless they are using two forms of birth control all the time.  NOTE: Due to the potential of COPEGUS^® to be transmitted in the semen it is recommended that one of the two methods be a barrier-type e.g. condom.

Women Only:

NOTE:  If you a woman, you cannot be pregnant, become pregnant, or breastfeed during the whole period of the study (up to 2 years).  If you are a man, your partner cannot be pregnant or become pregnant during the whole period of the study.  Please see the section on Contraceptive Requirements for additional information.

The safety of PEGASYS^® is not known, and COPEGUS^® may cause birth defects or death of an unborn child.  Women of childbearing potential must have a negative pregnancy test within 24 hours before starting the first dose of the study drug and every 4 weeks during the treatment and subsequent observation period (to be done at home).  Female subjects who are prematurely discontinued from treatment need to have a urine pregnancy test every 4 weeks for 24 weeks following the last dose of the study drug.  A repeat pregnancy test must be done if you miss any periods or your menstrual cycle becomes very irregular.

If you get pregnant while in this dtudy, there may be a risk of miscarriage, birth defects, or other unforseen medical conditions.  You must tell the study coordinator immediately.  The study doctor will advise you of the possible risks to your unborn child, the study drug will be stopped permanently.  Information during pregnancy and information concerning the outcome of your pregnancy will be collected by Hoffmann-La Roche Inc. and will be maintained on their safety database for this study.  This information will help further evaluate the effects of the treatment regimens on the course of pregnancy.  You must also notify the study doctor if you become pregnant within 6 months after the end of your treatment.

Men Only:

If your partnet becomes pregnant while you are taking part in this study, or within 6 months after stopping treatment, you must inform the study doctor.  You will be discontinued from this study.

As the risk to your partner and the baby are unknown, it is desirable for your partner to agree to provide information concerning the outcome of her pregnancy.  Your study doctor will work with Hoffmann-La Roche Inc. to organize this.  Your partner would be asked to sign a consent form to allow Hoffmann-La Roche to collect the information.  If you would like to see a copy of this form please ask your study doctor.

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INJURY STATEMENT:

In the event that you suffer and injury as a direct consequence of the research procedures described above, you will be examined by the study doctor and medical care will be given.  Hoffmann-La Roche Inc. will pay for the cost of medical treatment (over what the insurance company pays) for any injury that is directly a result of the treatment with the study medicines when they have been used as it states in the study protocol.  No other compensation will be provided by the University of Southern California for any injury you may suffer as a direct consequence of the non-negligent performance of the procedures described above.

You still have the right to make a medical claim through a legal system even if you sign this form, accept medical care, or accept payment for medical expenses.

<end INJURY STATEMENT section>