Racivir ® (RCV) is an experimental drug which means it is not approved for use by the United States Food and Drug Administration (FDA), but it can be used in research studies like this one. RCV (Racivir®) is part of a class of drugs known as "Nucleoside Reverse Transcriptase Inhibitors" (NRTIs), which are intended to block a further increase in the amount of HIV virus in the body. Laboratory research suggests that RCV (Racivir®) may be effective in patients who have developed resistance to other NRTIs, particularly 3TC (lamivudine, Epivir®). However, a study of RCV (Racivir®) has not been done with patients who have previously been treated with other HAART (Highly Active Antiretroviral Therapy -- taking multiple HIV drugs at once) medications including 3TC(lamivudine, Epivir®).

The purpose of this study is to evaluate the safety and effectiveness of RCV (Racivir®) when used together with other HIV drugs in people who have previously been treated with 3TC (lamivudine, Epivir®) and are failing with their current HAART treatments. This study will include a total of 60 HIV infected, HAART-experienced subjects currently receiving 3TC (lamivudine, Epivir®) as part of their HAART therapy. The study will take place at approximately 11 study sites in the US and Latin America.

Condition	Intervention	Phase
HIV	Drug: Racivir, a non-nucleoside reverse transcriptase inhibitor	Phase II

Further Study Details: 

Primary Outcomes: • Change from baseline in virological response of HIV (log10 HIV-RNA levels) at the end of week 2; • Change from baseline in CD4+ count at the end of week 2; • Adverse events
Secondary Outcomes: • Proportion of subjects in each treatment arm with viral load reduction  0.5 log10 from baseline; • Proportion of subjects in each treatment arm with viral load below 50 copies/mL
Expected Total Enrollment:  60

The study is divided into four periods: a ‘Screening’ period which can last up to 30 days in duration, a ‘Blinded Treatment’ period which can last up to 4 weeks in duration, a ‘Follow-up’ period which is 28 days in duration, and an ‘Open-label Treatment’ period that some subjects will be given the option to participate in and which can last up to 20 weeks.

If you decide to participate in this research study, you will be randomized, which is like picking chances from a hat, to get RCV (Racivir®) alone, 3TC (lamivudine, Epivir®) alone, or RCV and 3TC(lamivudine, Epivir®) in combination. This is a “double-blind study”. This means that neither you nor your study doctor and study staff will know if you are receiving RCV (Racivir®), 3TC (lamivudine, Epivir®), or RCV (Racivir®) and 3TC (lamivudine, Epivir®). This needs to be done to make sure we obtain the information we need to see if RCV (Racivir®) is safe and as effective as 3TC (lamivudine, Epivir®). In case of an emergency, the study doctor will be able to find out immediately what study drug you were receiving. With this exception, by signing the consent form you agree that you will not be able to find out what medications you are taking, because this is a “double-blind” study, it is necessary to use placebo tablets. A placebo is a tablet that does not contain any active drug, but is made to look just like the study drug.

You will be given three bottles of study medication. You will be asked to take one tablet from each bottle once a day by mouth, in addition to your current HAART drugs, not including 3TC. The 3TC in your current HAART regimen must be discontinued prior to you beginning study medication. It is important that you follow all directions when taking the study drugs.

After you complete the first 14 days of the blinded treatment period, you will be given the option to continue on your current randomized therapy, including your current study medication, for an additional 1-2 weeks. On Day 15, a blood sample will be collected from you to determine the amount of HIV virus in your blood. Once the results from that blood sample are available, you will be told how much the amount of HIV virus changed in your blood during the first 14 days of treatment. You will also be told if you were receiving RCV (Racivir®) alone, 3TC (lamivudine, Epivir®) alone, or a combination of RCV (Racivir®) and 3TC (lamivudine, Epivir®).

If you were receiving RCV (Racivir®), to continue in the open-label treatment period, the amount of virus in your blood must drop by at least 2/3 during the first 14 days of the blinded treatment period. For example, if you enter the study with 10,000 copies of the HIV virus per milliliter (ml) of blood, then to continue in the open-label period, your virus level must drop to 3,162 copies or less, per ml of blood. Open-label means that you and the study doctor or study staff will know what treatment you were receiving.

If the virus drops by at least 2/3, you will be given the option to enter an open-label treatment period. During the open-label period, you will receive 600 mg RCV (Racivir®) once daily along with your regular HAART medications. Before entering the open-label period, your study doctor may decide to change your other ARV medications. Participating subjects will be financially responsible for all medications, other than RCV (Racivir®), that your study doctor may prescribe for you.

Once your treatment is “unblinded” you may learn that you were not receiving any RCV (Racivir®) during the blinded treatment period. You may voluntarily decide to add 600 mg RCV (Racivir®) once daily to your other HAART medications. Your study doctor may decide to change your HAART medications at this time. After 2 weeks of RCV (Racivir®) based treatment, you will be asked to return to the study doctor’s office to have your blood drawn to determine the amount of HIV virus in your blood. You may continue on RCV (Racivir®) for up to an additional 2 weeks until the results from the blood test are available. If your viral load does not decline by at least 2/3, you will be withdrawn from the open-label portion of the study. You will be asked to return to the study doctor’s office for a final follow-up visit approximately 28 days after your last dose of RCV (Racivir®).

The open-label treatment period will last no longer than 20 weeks. During this study, you can receive up to 24 weeks of RCV (Racivir®) therapy. After you receive your last dose of study medication, you will enter the follow-up period for 28 days.

If you or the study doctor decides to withdraw from the study early, you will need to return to the study doctor’s office to have a follow-up visit approximately 28 days after your last dose of RCV (Racivir®).

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria: 1. Males and females who are between 18 years (or the legal age of consent, whichever is older) and 65 years of age. Females may be enrolled following a negative pregnancy test if: a) they are documented to be surgically sterile or post-menopausal [amenorrhea >1 year and FSH >30mU/mL] or

b) they are using a hormonal birth control method (oral contraceptives, contraceptive implants)

or

c) they are using a barrier method of contraception (male or female condoms, diaphragm, cervical cap) with a spermicide. 2. Subjects with a positive history of HIV-infection, documented by a licensed HIV antibody ELISA assay and confirmed either by Western blot, positive HIV blood culture, positive HIV serum antigen or plasma viremia. 3. Subjects currently on an accepted, stable HAART regimen that includes lamivudine for at least 60 days prior to screening. 4. Subjects who, in the opinion of the investigator, are failing their current HAART regimen. 5. Subjects who have an HIV-RNA copy number of ≥ 2000 copies/mL as determined by FDA-approved, Roche PCR assay (Amplicor HIV-1 Monitor® Test, v1.5 – Quantitative). 6. Subjects who have a CD4-lymphocyte count ≥ 50 cells/mm3. 7. Subjects who have the M184V HIV mutation, as determined by the FDA-approved Bayer assay, TRUGENE® HIV-1 Genotyping Kit and the OpenGene® DNA Sequencing System. 8. Subjects who are able and willing to provide written, informed consent. 9. Subjects who are able and willing to comply with the requirements of this study.

Exclusion Criteria: 1. Subjects who have a current or recent (< 30 days) opportunistic infection characteristic of AIDS (Category C according to the CDC Classification System for HIV-1 Infection, 1993 Revised Version). 2. Subjects currently on a (-)-FTC regimen. 3. Subjects with Q151M mutation. 4. Subjects with T69S insertions. 5. Female subjects who are pregnant or breastfeeding. 6. Subjects enrolled in other investigational drug protocols or subjects who have received other investigational agents within 30 days prior to the first dose of study medication. For investigational drugs with an elimination half-life greater than 15 days, this will be extended to 60 days. 7. Subjects with malabsorption syndromes possibly affecting drug absorption (e.g. Crohn’s disease, chronic pancreatitis, etc). 8. Subjects with acute hepatitis B and/or C, except for subjects who, at the discretion of the investigator, have a chronic, but stable hepatitis infection. 9. Subjects with the following laboratory parameters within 30 days prior to the first dose of study medication:

• Hemoglobin <10.0 g/dL • Absolute neutrophil count (ANC) <1000/mm3 • Platelet count <100,000/mm3 • AST or ALT >5 times the upper limit of normal, without the presence of an underlying illness, other than HIV or acute hepatitis, judged by the investigator to likely cause such chronic enzyme abnormalities • Pancreatic amylase >1.5 times the upper limit of normal. 10. Subjects who have received an HIV vaccination within 6 months prior to the first dose of study medication. 11. Subjects who have received radiation therapy or cytotoxic chemotherapeutic agents within 30 days prior to the first dose of study medication. 12. Subjects who, in the opinion of the investigator, are unable to comply with the dosing schedule and protocol evaluations.

Please refer to this study by ClinicalTrials.gov identifier  NCT00121979

Amanda L Beard, MS      609-613-4102    clinical@pharmasset.com

Illinois
      Northwestern University, Chicago,  Illinois,  60611,  United States; Recruiting
New York
      Jacobi Medical Center, Bronx,  New York,  10461,  United States; Recruiting
South Carolina
      Burnside Clinic, Columbia,  South Carolina,  29206,  United States; Recruiting
Argentina
      Fundacion Huesped Clinical Research, Buenos Aires,  C1202ABB,  Argentina; Recruiting
Mexico
      Instituto Nacional de Nutricion, Mexico City,  14000,  Mexico; Recruiting
Panama
      Medical Research Center Consultorio Royal Center, Republico de Panama,  Panama; Recruiting

Study chairs or principal investigators

Robert Murphy, MD,  Study Director,  Northwestern University   

Study ID Numbers:  CI-PSI-RCV-04-201
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 21, 2005
ClinicalTrials.gov Identifier:  NCT00121979
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-07-26