HIV InfectionsPhase 2VICTOR-E1NCT00243230
Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Participants (VICTOR-E1) (MK-7690-020/P03672)
A Phase 2 study testing Vicriviroc 30 mg, Vicriviroc 20 mg and Background ART Regimen in people with HIV Infections, run by Merck Sharp & Dohme LLC.
Trial summary
Vicriviroc (vye-kri-VYE-rock) is an investigational drug that belongs to a new class of drugs, called C-C chemokine receptor type 5 (CCR5) receptor blockers. This group of drugs blocks one of the ways human immunodeficiency virus (HIV) enters T-cells (the cells that fight infection). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Vicriviroc 30 mg, Vicriviroc 20 mg and Background ART Regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 116 participants
- Where
- No sites listed yet
- Study dates
- 19 Sep 2005to 17 Mar 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult participants with documented HIV infection with no detectable C-X-C Motif Chemokine Receptor 4 (CXCR4)
- Prior therapy for ≥3 months with ≥3 classes of currently marketed (US FDA-approved) antiretroviral agents (nucleoside reverse transcriptase inhibitor, NRTIs, non-nucleoside reverse transcriptase inhibitor (NNRTIs), protease inhibitor (PIs), or fusion inhibitors) at any time prior to screening
- HIV ribonucleic acid (RNA) ≥1000 copies/mL on a stable ART regimen for ≥6 weeks prior to Screening and ≥8 weeks prior to randomization
- ≥1 genotypically documented resistance mutation to a reverse transcriptase (RT) inhibitor and ≥1 primary resistance mutation to a PI
- Acceptable hematologic, renal and hepatic laboratory parameters
Who cannot join
- No history of previous malignancy (with the exceptions of cutaneous Kaposi's Sarcoma without visceral or mucosal involvement that resolved with highly active antiretroviral therapy (HAART) but without systemic anti-cancer treatment, and basal-cell carcinoma of skin surgically resected with disease-free margins on pathology exam)
- Treatment with cytotoxic cancer chemotherapy,
- Recurrent seizure, or central nervous system (CNS) condition or drug use predisposing to seizure in the opinion of the investigator
- No active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection
About this study
Official title: Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Subjects (VICTOR-E1)
Vicriviroc (vye-kri-VYE-rock) is an investigational drug that belongs to a new class of drugs, called C-C chemokine receptor type 5 (CCR5) receptor blockers. This group of drugs blocks one of the ways human immunodeficiency virus (HIV) enters T-cells (the cells that fight infection). The purpose of this 48-week study is to evaluate 2 dose levels of vicriviroc in participants with HIV who have not responded adequately to standard HIV treatments. This study was designed to evaluate the safety and efficacy of doses of vicriviroc, when taken in combination with other HIV drugs, in terms of ability to decrease the level of HIV (viral load) in the blood. The primary objective of the study was to evaluate antiviral efficacy of two doses of Vicriviroc maleate compared to placebo in combination with a protease inhibitor (PI)-containing optimized antiretroviral therapy (ART) regimen in CCR5-tropic HIV infected individuals failing a standard ART regimen.
Read the detailed description
This is a randomized, double-blind, placebo controlled, parallel-group, multi-center study of vicriviroc maleate in participants with HIV infected with CCR5-tropic virus only for whom standard antiretroviral treatment (ART) has failed. The study will evaluate the antiviral efficacy of two doses of vicriviroc (20 mg once daily (QD) and 30 mg QD) compared with placebo when added to optimized ART therapy. The optimized background regimen will be chosen by the investigator based on results of drug susceptibility tests, history of prior antiretroviral drug use by the participant, and drug toxicity. The background regimen must include at least 3 antiretroviral drugs (not including study drug), one of which must be a ritonavir-boosted protease inhibitor (≥100 mg ritonavir). There will be two interim analyses: when all participants have completed 12 weeks and 24 weeks of treatment, respectively. Based on the balance of safety and efficacy determined in these analyses, a dosage or dosages will be selected for further study in additional registrational trials. The primary efficacy analysis will be conducted when all participants have completed 48 weeks of treatment. After Week 48, participants who meet applicable criteria will be offered open label vicriviroc 30 mg QD, if appropriate, until the sponsor terminates the clinical development of vicriviroc. Additionally, participants who discontinue early from the study prior to Week 48 will be offered re-screening for the open label segment of the study.
- Conditions
- HIV Infections
- Being tested
- Vicriviroc 30 mg, Vicriviroc 20 mg, Placebo, Background ART Regimen
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vicriviroc 30 mgDrug
Also called SCH 417690
Three tablets of vicriviroc 10 mg once daily for 48 weeks (Double-blind Period) or for up to 45 months (Open Label Period).
Vicriviroc 20 mgDrug
Also called SCH 417690
Two tablets of vicriviroc 10 mg once daily for 48 weeks.
PlaceboDrug
Three tablets of placebo once daily for 48 weeks.
PlaceboDrug
Two tablets of placebo once daily for 48 weeks.
Background ART RegimenDrug
An open-label ritonavir-boosted optimized background ART regimen containing ≥3 drugs (including a protease inhibitor [PI]) selected for each individual study participant by the investigator. The optimized regimens most commonly include new nucleoside analogs (NRTIs) and a PI, usually "boosted" with concomitant ritonavir.
| Study group | Role | What they receive |
|---|---|---|
| Double-Blind - Vicriviroc 30 mg | Experimental | Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized antiretroviral therapy (ART) regimen containing a ritonavir-boosted protease inhibitor (PI/r) for 48 weeks. Receives: Drug: Vicriviroc 30 mg; Drug: Background ART Regimen |
| Double-Blind - Vicriviroc 20 mg | Experimental | Vicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Receives: Drug: Vicriviroc 20 mg; Drug: Placebo; Drug: Background ART Regimen |
| Double-Blind - Placebo | Placebo comparator | Placebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. Receives: Drug: Placebo; Drug: Background ART Regimen |
| Open-label - Vicriviroc 30 mg | Experimental | Vicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months. Receives: Drug: Vicriviroc 30 mg; Drug: Background ART Regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. Analysis was performed with a variance (ANOVA) model that adjusted for the treatment and stratification factors (intended enfuvirtide (T20) use in current newly-optimized background regimen (OBT) (Y/N) and HIV RNA at Screening (> or ≤100,000 copies/mL)).
Measured: Baseline and Week 48 of the Double-blind Period
Secondary outcomes (24)
Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero.
Measured: Baseline and 48 Weeks of the Double-blind Period
Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero.
Measured: Week 48 of the Double-blind Period
Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period
TLOVR defined as the time from randomization to either: 1. Failure to experience HIV RNA decline of ≥0.5 log10 from Baseline at Week 4, in which case time was set to 0; or 2. Rebound of HIV RNA to within 0.5 log10 of baseline value at any time after maximum suppression. HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero.
Measured: Up to 48 weeks of the Double-blind Period
Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing values of change from baseline were imputed by the average of immediately preceding and following non-missing values, and in any other cases, missing values were imputed by zero.
Measured: Baseline and Week 12 of the Double-blind Period
Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 c/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 c/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing values of change from baseline were imputed by the average of immediately preceding and following non-missing values, and in any other cases, missing values were imputed by zero.
Measured: Baseline and Week 24 of the Double-blind Period
Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken.
Measured: Baseline and Week 12 of the Double-blind Period
Change From Baseline CD4 Count at Week 24 of the Double-blind Period
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken.
Measured: Baseline and Week 24 of the Double-blind Period
Change From Baseline CD4 Count at Week 48 of the Double-blind Period
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken.
Measured: Baseline and Week 48 of the Double-blind Period
Change From Baseline CD4 Count at Month 42 of the Open Label Extension
Blood was collected and CD4+ cell count assessment was done by flow cytometry. Mean change from baseline in CD4 cell counts was determined. Any missing value was replaced by carrying forward baseline except if the immediately preceding and following value are available, in which case the arithmetic average of the two was used. If more than 1 CD4 count was available during a visit window, the value that was the closest to the time point of interest was used. If more than 1 pre-treatment CD4 value was available at baseline, the arithmetic mean of the 2 CD4 counts was taken. After completion of the Double-Blind Period, eligible participants could enroll in the Open Label Period and continue treatment.
Measured: Baseline and Month 42 of the Open Label Period
Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. HIV RNA <400 copies/mL is a less stringent measure of viral suppression and indicates that a participant responded to treatment.
Measured: Week 12 of the Double-blind Period
Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. HIV RNA <400 copies/mL is a less stringent measure of viral suppression and indicates that a participant responded to treatment.
Measured: Week 24 of the Double-blind Period
Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay (the lower quantification, [LOQ of 400 copies/mL]) and for HIV RNA below the LOQ, with the AMPLICOR HIV-1.5 UltraSensitive assay. HIV RNA <400 copies/mL is a less stringent measure of viral suppression (participant responded to treatment). HIV RNA < 50 copies/mL is a very stringent measure of viral suppression (participant achieved full virologic suppression). If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. Missing value for any reason will be imputed as non-responder except if the immediately preceding and following viral counts are both <50 copies/mL. Results are shown for Group 1. for participants with baseline HIV RNA <50 copies/mL, Group 2. baseline HIV RNA 50 to <400 copies/mL, and Group 3. baseline HIV RNA>400 copies/mL.
Measured: Up to 45 months of the Open Label Extension
Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period
The lower limit of HIV RNA <50 copies/mL was determined by the UltraSensitive assay. HIV RNA <50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason were imputed as non-responder except if the immediately preceding and following viral counts are both <50 copies/mL.
Measured: Week 12 of the Double-blind Period
Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period
The lower limit of HIV RNA <50 copies/mL was determined by the UltraSensitive assay. HIV RNA < 50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason will be imputed as non-responder except if the immediately preceding and following viral counts are both <50 copies/mL.
Measured: Week 24 of the Double-blind Period
Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period
The lower limit of HIV RNA <50 copies/mL was determined by the UltraSensitive assay. HIV RNA <50 copies/mL is a very stringent measure of viral suppression and indicates that a participant achieved full virologic suppression. Missing value for any reason were imputed as non-responder except if the immediately preceding and following viral counts are both <50 copies/mL.
Measured: Week 48 of the Double-blind Period
Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period
All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an Adjudication Committee of HIV experts. These experts did not participant in the study and reviewed the data without knowledge of treatment assignment. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least two of the three Adjudication Committee members. Their review consisted of available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, when applicable as well as autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used.
Measured: Up to 48 weeks of the Double-blind Period
Participants With AIDS-defining Events of the Open Label Extension
All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an Adjudication Committee of HIV experts, who did not participant in the study and reviewed the blinded data. Their review consisted of available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least 2 of 3 Adjudication Committee members. After completion of the Double-blind Period, eligible participants could enroll in the Open Label Period and continue treatment.
Measured: Up to 45 months of the Open Label Extension
Time to Occurrence of an AIDS-defining Event of the Double-blind Period
All potential AIDS-defining events (ADEs) identified by investigators and the sponsor were submitted with supporting clinical data to an independent and blinded Adjudication Committee of HIV experts. To be analyzed as an ADE, the event required concurrence on the diagnosis by at least 2 of the 3 Adjudication Committee members. Their review included available clinical and laboratory data, including relevant radiologic, endoscopic, and pathology assessments, when applicable as well as autopsy reports and/or hospital admission and discharge summaries. An independent radiologist was called upon when necessary. Guidelines for Diagnosis of AIDS-Defining Conditions (CDC's 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults) was used.
Measured: Up to 48 weeks of the Double-blind Period
Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period
Key pharmacokinetic (PK) parameters (maximum plasma concentration [Cmax], minimum plasma concentration [Cmin], area under the plasma concentration-time curve [AUC]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. Cmin is a measure of the minimum amount of drug in the plasma after the dose is given. Pharmacokinetics studies were not performed with participants receiving Placebo.
Measured: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period
Key pharmacokinetic (PK) parameters (maximum plasma concentration [Cmax], minimum plasma concentration [Cmin], area under the plasma concentration-time curve [AUC]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Pharmacokinetics studies were not performed with participants receiving Placebo.
Measured: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period
Key pharmacokinetic (PK) parameters (maximum plasma concentration [Cmax], minimum plasma concentration [Cmin], area under the plasma concentration-time curve [AUC]) were estimated using a population PK modeling approach based on a two-compartment model with first-order absorption and elimination. AUC is a measure of the mean concentration levels of drug in the plasma after the dose. Pharmacokinetics studies were not performed with participants receiving Placebo.
Measured: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Participants With Detectable Vicriviroc Resistance of the Double-blind Period
Resistance testing was performed at Baseline and again at the time of virologic failure or study discontinuation using the Phenosense GT assay (Monogram Biosciences, South San Francisco, CA). This assay used a combination of genotypic and phenotypic resistance techniques to determine an overall sensitivity score (OSS). The OSS represents the total number of drugs in the optimized background regimen (OBT) to which the virus was fully susceptible. Partial sensitivity is not counted towards the OSS. VCV susceptibility testing was performed with a maximal percent inhibition (MPI) plateau value of <85% as a cutoff for resistance.
Measured: Up to 48 weeks of the Double-blind Period
Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period
Viral tropism was determined using the Monogram Trofile assay and antiviral drug susceptibility was measured by Monogram PhenoSense GT assay, based on both genotypic and phenotypic sensitivity of HIV isolates. The lower limit of sensitivity of the Trofile assay employed in this study for detection of minor X-4 using variants was 5-10%.
Measured: Up to 48 weeks of the Double-blind Period
Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period
Viral tropism was determined using the Monogram Trofile assay and antiviral drug susceptibility was measured by Monogram PhenoSense GT assay, based on both genotypic and phenotypic sensitivity of HIV isolates. The lower limit of sensitivity of the Trofile assay employed in this study for detection of minor X-4 using variants was 5-10%. Participants with emergence of CXCR4 tropism who had a concomitant decline in CD4 count by ≥50% below baseline was also computed.
Measured: Up to 48 weeks of the Double-blind Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2005 (estimated)
- Study start19 Sep 2005
- Primary completion19 Oct 2007
- Study completion17 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00243230
- Sponsor's protocol ID
- P03672
- Other IDs
- 2005-001057-21, MK-7690-020, P03672, 2005
- Acronym
- VICTOR-E1
- Status last verified
- May 2021
- First submitted
- 20 Oct 2005
- Last updated
- 8 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Suleiman J, Zingman BS, Diaz RS, Madruga JV, DeJesus E, Slim J, Mak C, Lee E, McCarthy MC, Dunkle LM, Walmsley S. Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial. J Infect Dis. 2010 Feb 15;201(4):590-9. doi: 10.1086/650342.
PubMed 20064072
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vicriviroc (SCH 417690) in Combination Treatment With Optimized ART Regimen in Experienced Subjects (VICTOR-E1)
- ClinicalTrials.gov ID
- NCT00243230
- Acronym / sponsor ID
- VICTOR-E1 / P03672
- Conditions
- HIV Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 19 Sep 2005 (actual)
- Primary completion
- 19 Oct 2007 (actual)
- Study completion
- 17 Mar 2011 (actual)
- First posted
- 21 Oct 2005 (estimated)
- Results
- Posted 8 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vicriviroc (vye-kri-VYE-rock) is an investigational drug that belongs to a new class of drugs, called C-C chemokine receptor type 5 (CCR5) receptor blockers. This group of drugs blocks one of the ways human immunodeficiency virus (HIV) enters T-cells (the cells that fight infection). The purpose of this 48-week study is to evaluate 2 dose levels of vicriviroc in participants with HIV who have not responded adequately to standard HIV treatments. This study was designed to evaluate the safety and efficacy of doses of vicriviroc, when taken in combination with other HIV drugs, in terms of ability to decrease the level of HIV (viral load) in the blood. The primary objective of the study was to evaluate antiviral efficacy of two doses of Vicriviroc maleate compared to placebo in combination with a protease inhibitor (PI)-containing optimized antiretroviral therapy (ART) regimen in CCR5-tropic HIV infected individuals failing a standard ART regimen.
Detailed description
This is a randomized, double-blind, placebo controlled, parallel-group, multi-center study of vicriviroc maleate in participants with HIV infected with CCR5-tropic virus only for whom standard antiretroviral treatment (ART) has failed. The study will evaluate the antiviral efficacy of two doses of vicriviroc (20 mg once daily (QD) and 30 mg QD) compared with placebo when added to optimized ART therapy. The optimized background regimen will be chosen by the investigator based on results of drug susceptibility tests, history of prior antiretroviral drug use by the participant, and drug toxicity. The background regimen must include at least 3 antiretroviral drugs (not including study drug), one of which must be a ritonavir-boosted protease inhibitor (≥100 mg ritonavir). There will be two interim analyses: when all participants have completed 12 weeks and 24 weeks of treatment, respectively. Based on the balance of safety and efficacy determined in these analyses, a dosage or dosages will be selected for further study in additional registrational trials. The primary efficacy analysis will be conducted when all participants have completed 48 weeks of treatment. After Week 48, participants who meet applicable criteria will be offered open label vicriviroc 30 mg QD, if appropriate, until the sponsor terminates the clinical development of vicriviroc. Additionally, participants who discontinue early from the study prior to Week 48 will be offered re-screening for the open label segment of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Double-Blind - Vicriviroc 30 mg | Experimental | Drug: Vicriviroc 30 mg, Drug: Background ART RegimenVicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized antiretroviral therapy (ART) regimen containing a ritonavir-boosted protease inhibitor (PI/r) for 48 weeks. |
| Double-Blind - Vicriviroc 20 mg | Experimental | Drug: Vicriviroc 20 mg, Drug: Placebo, Drug: Background ART RegimenVicriviroc 20 mg QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. |
| Double-Blind - Placebo | Placebo comparator | Drug: Placebo, Drug: Background ART RegimenPlacebo QD, PO, plus an open-label optimized ART regimen containing a PI/r for 48 weeks. |
| Open-label - Vicriviroc 30 mg | Experimental | Drug: Vicriviroc 30 mg, Drug: Background ART RegimenVicriviroc 30 mg once daily (QD), orally (PO), plus an open-label optimized ART regimen containing a ritonavir-boosted protease inhibitor (PI/r) for up to 45 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Adult participants with documented HIV infection with no detectable C-X-C Motif Chemokine Receptor 4 (CXCR4)
- Prior therapy for ≥3 months with ≥3 classes of currently marketed (US FDA-approved) antiretroviral agents (nucleoside reverse transcriptase inhibitor, NRTIs, non-nucleoside reverse transcriptase inhibitor (NNRTIs), protease inhibitor (PIs), or fusion inhibitors) at any time prior to screening
- HIV ribonucleic acid (RNA) ≥1000 copies/mL on a stable ART regimen for ≥6 weeks prior to Screening and ≥8 weeks prior to randomization
- ≥1 genotypically documented resistance mutation to a reverse transcriptase (RT) inhibitor and ≥1 primary resistance mutation to a PI
- Acceptable hematologic, renal and hepatic laboratory parameters
Key exclusion criteria (4 listed)
- No history of previous malignancy (with the exceptions of cutaneous Kaposi's Sarcoma without visceral or mucosal involvement that resolved with highly active antiretroviral therapy (HAART) but without systemic anti-cancer treatment, and basal-cell carcinoma of skin surgically resected with disease-free margins on pathology exam)
- Treatment with cytotoxic cancer chemotherapy,
- Recurrent seizure, or central nervous system (CNS) condition or drug use predisposing to seizure in the opinion of the investigator
- No active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vicriviroc 30 mgAlso: SCH 417690Three tablets of vicriviroc 10 mg once daily for 48 weeks (Double-blind Period) or for up to 45 months (Open Label Period). | Drug | Double-Blind - Vicriviroc 30 mg, Open-label - Vicriviroc 30 mg |
| Vicriviroc 20 mgAlso: SCH 417690Two tablets of vicriviroc 10 mg once daily for 48 weeks. | Drug | Double-Blind - Vicriviroc 20 mg |
| PlaceboThree tablets of placebo once daily for 48 weeks. | Drug | Double-Blind - Placebo |
| PlaceboTwo tablets of placebo once daily for 48 weeks. | Drug | Double-Blind - Vicriviroc 20 mg |
| Background ART RegimenAn open-label ritonavir-boosted optimized background ART regimen containing ≥3 drugs (including a protease inhibitor [PI]) selected for each individual study participant by the investigator. The optimized regimens most commonly include new nucleoside analogs (NRTIs) and a PI, usually "boosted" with concomitant ritonavir. | Drug | Double-Blind - Placebo, Double-Blind - Vicriviroc 20 mg, Double-Blind - Vicriviroc 30 mg, Open-label - Vicriviroc 30 mg |
Primary outcome
Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period
Time frame: Baseline and Week 48 of the Double-blind Period
HIV RNA was measured by AMPLICOR HIV-1 MONITOR Standard assay. For participants who had HIV RNA below the lower quantification of the Standard assay (LOQ of 400 copies/mL), the AMPLICOR HIV-1.5 UltraSensitive assay was performed. If the HIV RNA measurement was below the lower quantification of the UltraSensitive assay (LOQ of 50 copies/mL), a value of 49 was imputed. If a continuing participant has a missing HIV RNA value at the time point of interest, the geometric mean of immediately preceding and following values was used. If the participants had no subsequent following value or discontinued study treatment before the time point of interest, then the change from baseline was set to zero. Analysis was performed with a variance (ANOVA) model that adjusted for the treatment and stratification factors (intended enfuvirtide (T20) use in current newly-optimized background regimen (OBT) (Y/N) and HIV RNA at Screening (> or ≤100,000 copies/mL)).
24 secondary outcomes
Participants With ≥1.0 log10 Change From Baseline HIV RNA at Week 48 of the Double-blind Period
Time frame: Baseline and 48 Weeks of the Double-blind Period
Participants With HIV RNA <400 Copies/mL at Week 48 of the Double-blind Period
Time frame: Week 48 of the Double-blind Period
Participants With a Time to Loss of Virologic Response (TLOVR) Based on 0.5 Log10 Reduction by 48 Weeks of the Double-blind Period
Time frame: Up to 48 weeks of the Double-blind Period
Change From Baseline in Log10 HIV RNA at Week 12 of the Double-blind Period
Time frame: Baseline and Week 12 of the Double-blind Period
Change From Baseline in Log10 HIV RNA at Week 24 of the Double-blind Period
Time frame: Baseline and Week 24 of the Double-blind Period
Change From Baseline CD4 Cells Count at Week 12 of the Double-blind Period
Time frame: Baseline and Week 12 of the Double-blind Period
Change From Baseline CD4 Count at Week 24 of the Double-blind Period
Time frame: Baseline and Week 24 of the Double-blind Period
Change From Baseline CD4 Count at Week 48 of the Double-blind Period
Time frame: Baseline and Week 48 of the Double-blind Period
Change From Baseline CD4 Count at Month 42 of the Open Label Extension
Time frame: Baseline and Month 42 of the Open Label Period
Participants With <400 Copies/mL HIV RNA at Week 12 of the Double-blind Period
Time frame: Week 12 of the Double-blind Period
Participants With <400 Copies/mL HIV RNA at Week 24 of the Double-blind Period
Time frame: Week 24 of the Double-blind Period
Number of Participants With <50, 50 to <400, and ≥400 Copies/mL HIV RNA of the Open Label Extension
Time frame: Up to 45 months of the Open Label Extension
Participants With <50 Copies/mL HIV RNA at Week 12 of the Double-blind Period
Time frame: Week 12 of the Double-blind Period
Participants With <50 Copies/mL HIV RNA at Week 24 of the Double-blind Period
Time frame: Week 24 of the Double-blind Period
Participants With <50 Copies/mL HIV RNA at Week 48 of the Double-blind Period
Time frame: Week 48 of the Double-blind Period
Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Events of the Double-blind Period
Time frame: Up to 48 weeks of the Double-blind Period
Participants With AIDS-defining Events of the Open Label Extension
Time frame: Up to 45 months of the Open Label Extension
Time to Occurrence of an AIDS-defining Event of the Double-blind Period
Time frame: Up to 48 weeks of the Double-blind Period
Observed Minimum Serum Concentration of Vicriviroc (Cmin) of the Double-blind Period
Time frame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Observed Maximum (Peak) Plasma Concentration of Vicriviroc (Cmax) of the Double-blind Period
Time frame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Area Under the Plasma Concentration Versus Time Curve of Vicriviroc (AUC) of the Double-blind Period
Time frame: Two blood samples 2 hours apart on Week 4, Week 12, and Week 24 of the Double-blind Period
Participants With Detectable Vicriviroc Resistance of the Double-blind Period
Time frame: Up to 48 weeks of the Double-blind Period
Participants With Detectable C-X-C Chemokine Receptor Type 4 (CXCR4)-Tropic Virus of the Double-blind Period
Time frame: Up to 48 weeks of the Double-blind Period
Participants With Detectable CXCR4-Tropic Virus and Immune Decline (≥50% Fall in CD4 Count From Baseline) of the Double-blind Period
Time frame: Up to 48 weeks of the Double-blind Period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 20064072Suleiman J, Zingman BS, Diaz RS, Madruga JV, DeJesus E, Slim J, Mak C, Lee E, McCarthy MC, Dunkle LM, Walmsley S. Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial. J Infect Dis. 2010 Feb 15;201(4):590-9. doi: 10.1086/650342.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vicriviroc 30 mg, Vicriviroc 20 mg and Background ART Regimen in people with HIV Infections, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Log10 Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) at Week 48 of the Double-blind Period (time frame: Baseline and Week 48 of the Double-blind Period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00243230, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jun 2021.