Studies

STUDIES

CURRENT

Trizivir + Efavirenz (Sustiva): Protocol ESS40013

This is a 96 week phase IV study of treatment with Trizivir + Efavirenz. Initial treatment for 48 weeks is then followed by an additional 48 week randomization to open label maintenance treatment with Trizivir with or without Efavirenz. This study is for naВ•ve patients, or individuals never having been treated with antiretroviral medications.

Second Generation Non-nucleoside Phase 2 Protocol 083

This is the new second generation non-nucloeside reverse transcriptase inhibitor (DPC-083) - study that is randomized double-blind of two doses of DPC 083 in combination with open-label nucleoside analog reverse transcriptase inhibitors in HIV-1 infected patients who are failing treatment with a non-nucleoside reverse transcriptase inhibitor-containing regimen. This new agent is considered a true second generation NNRTI, promising to be an effective antiviral against resistance mutants of other currently available non-nukes.

FTC (Emtricitabine) vs d4T

FTC is a new potent nucleoside analog. In-vitro studies demonstrated FTC to be more potent than 3TC. This study is a randomized double blind study comparing two arms: FTC +ddI and Sustiva vs d4T + ddI + Sustiva. Patients must be antiretroviral naВ•ve and have viral loads greater than 5000 copies/ ml.

Tenofovir DF (PMPA Prodrug) Protocol 903

Tenofovir is part of a new class of agents called nucleotide reverse transcriptase inhibitors. This study is for naВ•ve patients, or patients that have never been on HIV therapy. It is a randomized double-blind in combination with 3TC and Sustiva vs. D4T, 3TC and Sustiva. The study is a 48 week study, but promises to continue till the drugГ•s approval.

PMPA Prodrug - Tenofovir Protocol 907 (Phase 3)

This is a part of the new class of agents called nucleotide reverse transcriptase inhibitors. The study keeps patients on their already stable cocktail but adds this new potent agent to the regimen. This phase III, 48 week study is for patients who have been on stable therapy and who have viral loads between 400 and 10,000.

Tenofovir 910

This is simply the extension phase of several Tenofovir studies. Patients who are or were on phase II or phase III Tenofovir studies are transitioned into this protocol. They continue receiving open-label drug, while long-term safety and monitoring continues.

Lipodystrophy and/or Elevated Lactate Levels Switch Study Protocol ESS4000

This study is to assess the regression of hyperlactatemia (elevated lactic acid levels in the blood) and to evaluate the regression of lipodystrophy in HIV-1 positive individuals (TARHEEL Protocol).Experienced patients will be switched, open label to ziagen from d4T. NaВ•ve patients will be placed on Combivir. Intensification will be permitted in the event of loss of virologic control.

L2-7001 - Interleukin-2

This is a phase II, 6 month study examines 3 doses of a new formulation of IL-2, that appears to be three times more potent and with less side effects than the currently used IL-2. The study eligibility includes patients with T cell counts between 300 and 500 cells. Viral loads should be less than 10,000 copies. Patients will be randomized to receive either the L2 form of IL2 or Proleukin IL2 twice daily (split dosing) for 5 days every two months. Some patients will be asked to be tested for IL2 blood levels.

Lipodystrophy and Fat Redistribution Syndrome

This research involves testing to examine the various relationships of a variety of factors that may contribute to the development of lipodystrophy and fat redistribution. The initial stage of the study is retrospective and examines the patientГ•s past medical history. The second phase of the study will include DEXA testing for body composition as well as single slice abdominal cat scanning to examine visceral (internal) body fat development.

Anogenital Herpes Treatment with Resiquimod (R-848)

This is a phase II randomized double-blind dose frequency response study of topical resiquimod gel applied to the herpes lesions once, twice or three times per week for recurrences to prevent future recurrences. Risiquimod is a topical treatment that works by stimulating oneГ•s own immune system to act against the herpes infection. This is for patients who are not immune compromised (HIV-negative).

DMP 266 - Sustiva + Crixivan

DMP 266 is a potent non-nucleoside reverse transcriptase inhibitor (NNTRI) that inhibits HIV production in HIV infected cells. A 2 year phase II/III multicenter, randomized, open-label study to compare antiretroviral activity and tolerability of three different combination regimens (DMP 266 + Crixivan, DMP 266 + AZT = 3TC, Crixivan = AZT + 3TC) in HIV-infected patients. Patients must be asymptomatic or mildly symptomatic, have a CD4 cell count greater than or equal to 50 cells/mm, and a viral load greater than or equal to 10,000 copies/mL. Patients will have received no prior treatment with DMP 266, 3TC, nevirapine, delavirdine, or any protease inhibitor.

Passive Immunotherapy with CMV Intravenous Immunoglulin

CMV IVIG is a preparation that contains high titers of antibodies of CMV (Cytomegalovirus). CMV is often a cause of opportunistic disease in AIDS. This off-label treatment is available to patients with CMV disease (i.e., CMV Retinitis, esophagitis, gastritis, or systemic disease, etc).

Passive Immunotherapy with Intravenous Immunoglovulin

IVIG is a lyphilized preparation of intact immunogobulin G (IgG) from pooled plasma and is not chemically altered. This broad range of antibodies is capable of neutralizing microbes and toxins against bacterial and viral antigens of various infectious diseases. This off-label treatment is available to patients with recurrent bacterial infections and/or history of an opportunistic disease. IVIG is administered monthly with close monitoring.

Interleuken-2 (IL-2)

Open-label interleuken-2 is a cytokine (natural substance produced by cells) that may stimulate T-cells increases. This off-label use of this drug for patients with CD4 T-cells greater than 100. The drug is administered by subcutaneuos injection daily for 5 consecutive days every 8 weeks.

Past Studies

Tenofovir DF (PMPA Prodrug) Protocol 903

PMPA Prodrug - Tenofovir Protocol 907 (Phase 3)

Lipodystrophy and/or Elevated Lactate Levels Switch Study

L2-7001 - Interleukin-2

FTC (Emtricitabine) vs d4T

Lipodystrophy and Fat Redistribution Syndrome

Protease Failure Гђ Study NZTA4008

This is a phase IV study for patients who are failing their initial protease inhibitor containing regimen in combination with 3TC and AZT or d4T. This study investigates three alternative regimens utilizing the drugs: Abacavir, Sustiva, ddI and Hydroxyurea. Patients are randomized to an open label regimen and must have CD4 T cell count > 200 cells and viral load between 400 and 50,000 copies/ml.

Substitution with Sustiva Гђ Study DMP 266-049

This is a phase IV, open label randomized study to determine the safety and duration of effect of regimens comparing continued therapy with protease inhibitors vs protease inhibitor substitution with Sustiva. Randomization will occur in 3:1 ratio, substitution vs. continued treatment with protease inhibitors. Patients will have skin-fold/anthropomorphic (weight and body circumference measurements) to determine whether the patient has lipodystrophy. Laboratory tests include lipid profiles (cholesterol and triglycerides).

Г’Nice Study:Г“ Crixivan combined with Norvir

This is a phase IV study for patients who remain with viral loads below 500 and who are on Crixivan with two other NucГ•s. The study is for 24 weeks. 3 of 4 patients will have their Crixivan dose reduced to one pill twice daily in combination with 400 mg of Norvir, both to be taken with food. One patient of every 4 will continue on their regular Crixivan dosing but will eventually be changed to the Crixivan /Norvir combination regimen at 12 weeks.

PMPA PRODRUG Study (phase 2)

PMPA is a potent nucleotide reverse transcriptase inhibitor that inhibits HIV production in HIV infected cells. A 48 week phase II, randomized double-blind study to evaluate the safety and antiviral activity of the addition of PMPA Prodrug to stable combination regimens. Patients must have a viral load > 400 and < 50,000 copies/ml and must be on stable antiretroviral therapy (including protease inhibitors) of no more than 3 active agents for 8 weeks. Hydroxyurea as a fourth drug is permitted. Patients currently taking adefovir cannot be enrolled.

Salvage for Protease Inhibitor Failures with MKC-442

MKC-442 is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV production. This 48 week randomized, double-blind study is enrolling patients failing protease inhibitor combinations and compares antiretroviral activity and tolerability of D4T, DDI, and Hydroxyurea with and without MKC-422. The study will involve 3 arms. Patients with viral loads >5000 and < 50,000 copies/ml will be randomized to receive either MKC-422 or placebo in combination with D4T, DDI and Hydroxyurea. Patients with viral loads > 50,000 copies/ml will receive open-label MKC-422. Patients must have failed a protease-containing regimen and be NNRTI naive.

DMP 266 - Sustiva + Crixivan

Passive Immunotherapy with CMV Intravenous Immunoglulin

HIV Anemia with Weekly Procrit Гђ Protocol PR98-29-002

Erythropoietin (Procrit) is a protein hormone, normally produced by the kidneys, and has been shown to significantly increase red blood cell count. This is a 16 week open label study using weekly injections of Procrit for patients with hemoglobins less than 11 g/dl. There is no placebo treatment and all qualified patients receive open label drug. The specific dosing requirement is titrated during the study.

Passive Immunotherapy with Intravenous Immunoglovulin

Interleuken-2 (IL-2)

Past Studies (February/March 2000)

PMPA Prodrug - Tenofovir Protocol 907 (Phase 3)

'Nice Study:' Crixivan combined with Norvir

This is a phase IV study for patients who remain with viral loads below 500 and who are on Crixivan with two other Nuc's. The study is for 24 weeks. 3 of 4 patients will have their Crixivan dose reduced to one pill twice daily in combination with 400 mg of Norvir, both to be taken with food. One patient of every 4 will continue on their regular Crixivan dosing but will eventually be changed to the Crixivan /Norvir combination regimen at 12 weeks.

L2-7001 - Interleukin-2

FTC (Emtricitabine) vs. Abacavir

FTC is a new potent nucleoside analog (NRTI). In-vitro studies have demonstrated FTC to be more potent than 3TC. This study is a randomized open-label 48 weeks trial comparing two arms: Arm 1 is FTC + d4T+ Sustiva; Arm 2 is Abacavir + d4T + Sustiva. Patients must be antiretroviral-drug naive and have a viral load greater than 5000 copies/ml.

Protease Failure Гђ Study NZTA4008

Substitution with Sustiva Гђ Study DMP 266-049

PMPA PRODRUG Study (phase 2)

Salvage for Protease Inhibitor Failures with MKC-442

MKC-442 + Viracept

MKC 442 is a new non nuceleoside RT inhibitor (NNRTI) in combination with Viracept, a potent protease inhibitor that is being studied in combination with a choice of reverse transcriptase inhibitors. This study is for patients of two groups: 1) patients naive to drug therapy and 2) patients having been on RT inhibitors but not experienced with protease inhibitors nor NNRTI's.

141W94 (Vertex Pharm. Protease Inhibitor) combined with 1592U89 (Abacavir) and Combivir (3TC/AZT) vs. Combivir with Viracept

Open-label, randomized, to compare the long-term durability of viral suppression with a four-drug regiment to that of a three-drug regimen. Patients must be antiretroviral-naive and have a RNA PCR (viral load) of >5,000 copies/ml. Duration: 48 weeks plus extension. Failing patients will be given the option of modifying their regimen according to best practice guided by genotypic and phenotypic data.

DMP 266 - Sustiva + Crixivan

HIV Anemia with Weekly Procrit Гђ Protocol PR98-29-002

Interleuken-2 (IL-2)

Passive Immunotherapy with CMV Intravenous Immunoglulin

Passive Immunotherapy with Intravenous Immunoglovulin

Lipodystrophy and Fat Redistribution Syndrome

PREVIOUS STUDIES

PMPN PRODRUG Study

PMPA is a potent nucleotide reverse transcriptase inhibitor that inhibits HPV production in HIV infected cells. A 48 week phase II, randomized double blind study to evaluate the safety and antiviral activity of the addition of PMPA Prodrug to stable combination regimens. Patients must have a viral load > 400 and < 50,000 copies/ml and must be on stable antiretroviral therapy (including protease inhibitors) of no more than 3 active agents for 8 weeks. Hydroxyurea as a fourth drug is permitted. Patients currently taking adefovir cannot be enrolled.

Salvage for Protease Inhibitor Failures with MKC442

MKC 442 is a potent non nucleoside reverse transcriptase inhibitor (NNRTI) that inhibits HIV production. This 48 week randomized, double-blind study is enrolling patients failing protease inhibitor combinations and compares antiretroviral activity and tolerability of D4T, DDL and Hydroxyurea with and without MKC 422. The study will involve 3 arms. Patients with viral loads >5000 and < 50,000 copies/ml will be randomized to receive either MKC 422 or placebo in combination with D4T, DDI and Hydroxyurea. Patients with viral loads > 50,000 copies/ml will receive open-label MKC 422. Patients must have failed a protease containing regimen and be NNRTI naive.

MKC442 + Viracept

141W94 (Vertex Pharm. Protease Inhibitor) combined with 1592U89 (Abacavir) and Combivir (3TC / AZT) vs. Combivir with Viracept

Open-label, randomized, to compare the long term durability of viral suppression with a four drug regiment to that of a three drug regimen. Patients must be antiretroviral naive and have a RNA PCR (viral load) of >5,000 copies/mI. Duration: 48 weeks plus extension. Failing patients will be given the option of modifying their regimen according to best practice guided by genotypic and phenotypic data.

DMP 266 Sustiva + Crixivan

DMP 266 is a potent non nucleoside reverse transcriptase inhibitor (NNTRI) that inhibits HIV production in HIV infected cells. A 2 year phase II/III multicenter, randomized, open label study to compare antiretroviral activity and tolerability of three different combination regimens ( DMP 266 + Crixivan, DMP 266 + AZT = 3TC, Crixivan = AZT + 3TC ) in HIV infected patients. Patients must be asympromatic or mildly symptomatic, have a CD4 cell count greater than or equal to 50 cells/mm3 and a viral load greater than or equal to 10,000 copies/mL. Patients will have received no prior treatment with DMP 266, 3TC, nevirapine, delavirdine, or any protease inhibitor.

Oral Lobucavir for New CMV Retinitis

Oral Lobucavir is a new antiviral that has activity against multiple viruses, including CMV, Herpes, Hepatitis B and certain intracellular forms of HIV. This study is for patients with newly diagnosed CMV disease of the eye (retinitis). All patients will have a Ganciclovir intervitreal implant followed by randomization to one of five treatment arms: Three arms contain different doses of oral lobucavir, one arm is standard oral ganciclovir the one arm (10 / 90 patients) will be randomized to placebo. After 4 weeks there is a two week wash out period, at which time all patients will get open label lobucavir.

Oral Lobucavir in the Suppression of Recurrent Episodes of Genital Herpes

A randomized, double blind Phase III study to evaluate the safety and efficacy of lobucavir in suppressing genital herpes outbreaks in patients with a history of recurrent genital herpes. Patients will be randomized to three treatment arms. Two arms contain two different doses of lobucavir and the other will be randomized to placebo. If three recurrences have occurred, the patient will be receive open label lobucavir. Patients must be immunocompetent (HIV negative) and have had at least six episodes of genital herpes within the last 12 months.

Salk Vaccine "Remune”

This therapeutic vaccine (HIV specific immune based therapy) is designed to stimulate an immune response specifically against HIV. This Phase III clinical trial will evaluate the effect of "Remune” on disease progression. Previous studies showed that treatment can slow both viral replication and the decline of CD4 cells in comparison to that of the control group. Entry to the trial is limited to persons with T-cells between 300-500, requiring at least three months of stable antiretroviral use. The therapeutic vaccine is injected once every three months without restrictions on any antiviral therapies or combinations you may be currently taking.

Interleuken2 (IL2)

Open label interleuken 2 is a cytokine (natural substance produced by cells) that may stimulate T cells increases. This off abel use of this drug for patients with CD4 T cells greater than 100. The drug is administered by subcutaneuos injection daily for 5 consecutive days every 8 weeks.

Passive Immunotherapy with CMV Intravenous Immunoglulin

CMV IVIG is a preparation that contains high titers of antibodies of CMV (Cytomegalovirus). CMV is often a cause of opportunistic disease in AIDS. This off label treatment is available to patients with CMV disease (i.e., CMV Retinitis, esophagitis, gastritis, or systemic disease, etc).

Passive Immunotherapy with Intravenous Immunoglovulin

IVIG is a lyphilized preparation of intact immunogobulin G (IgG) from pooled plasma and is not chemically altered. This broad range of antibodies is capable of neutralizing microbes and toxins against bacterial and viral antigens of various infectious diseases. This off label treatment is available to patients with recurrent bacterial infections and/or history of an opportunistic disease. IVIG is administered monthly with dose monitoring.