E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV infection (R5 tropism only) with previous therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10200172 |
E.1.2 | Term | <Manually entered code. Term in E.1.1> |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To confirm the hypothesis that vicriviroc 30 mg QD provides added benefit in plasma HIV-1 RNA reduction when added to optimized background therapy (OBT), as measured by the proportion of subjects with HIV RNA <50 copies/mL at Week 48. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of vicriviroc compared to placebo, each in combination with OBT. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. A subject must give written informed consent prior to screening for this study
2. A subject must be willing and able to adhere to dose and visit schedules
3. A subject must be at least 16 years of age (or minimum age that defines an adult as determined by local regulatory authorities or legal requirements) at the time of randomization, of either sex, and of any race
4. A subject must be infected with HIV-1 virus, as documented by a positive assay for HIV-1 RNA in plasma, prior to Screening
5. A subject must have plasma HIV-1 RNA >1000 copies/mL within 60 days of randomization, either
a) on a stable regimen of 3 or more antiretroviral drugs for at least 4 weeks at time of Screening, OR b) on no antiretroviral agents, for ≥4 weeks prior to Screening
6. Subjects must be ART-experienced and have documented resistance (as determined by the Monogram GeneSEq or PhenoSense HIV Drug Resistance assay) to at least 2 of the following 3 drug classes: NRTI, NNRTI or PI
OR
Antiretroviral class experience ≥6 months (sequential or cumulative) with at least two of the following:
a) one NRTI b) one NNRTI c) two PIs (excluding low dose ritonavir)
7. Subjects must be willing to begin newly optimized background therapy (OBT) containing at least 3 drugs at time of randomization, one of which must be a ritonavir-boosted PI. The OBT must contain at least 2 active drugs
Note: If tipranavir is used as part of a subject’s OBT, liver function tests must be performed at initiation of therapy and monitored frequently throughout the duration of treatment. Subjects must be followed closely and investigators must be vigilant for the appearance of signs or symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea, jaundice, bilirubinemia, acholic stools, and liver tenderness, especially in those with liver enzyme abnormalities or history of chronic liver disease. Tipranavir should not be given to subjects with moderate to severe liver disease
8. QTc interval (corrected by the Bazett method) read by the Central EKG Cardiologist must be <470 msec for female subjects and <450 msec for male subjects
9. Subjects must have acceptable hematologic, renal, and hepatic laboratory parameters: Platelet count ≥75,000/µL; hemoglobin ≥9.0 g/dL; absolute neutrophil count ≥750/µL; serum creatinine ≤2 x ULN; AST (SGOT) and ALT (SGPT) ≤5 x ULN; alkaline phosphatase ≤5 x ULN; total bilirubin ≤2.5 x ULN. For subjects receiving indinavir or atazanavir, or known to have Gilbert’s syndrome, the total bilirubin must be ≤5 x ULN and in fractionation must demonstrate that the increase is due to an elevated indirect bilirubin. Subjects with chronic hepatitis B or C may be enrolled if they have stable liver disease and liver enzymes in the following ranges: AST (SGOT) and ALT (SGPT) ≤3 x ULN; alkaline phosphatase ≤5 x ULN; total bilirubin ≤2.5 x ULN
10. Women of child-bearing potential must agree to use a medically accepted method of contraception prior to receiving protocol-specified medication, and for 2 months after stopping the medication. Acceptable methods include:
a. condoms (male or female), with or without a spermicidal agent (Note: in some countries, use of spermicide with condoms may be required) b. diaphragm or cervical cap with spermicide c. sponge with spermicide d. surgical sterilization (eg, hysterectomy or bilateral oophorectomy)
Note: Systemic hormonal contraceptives may not be effective when used concomitantly with ritonavir and other protease inhibitors, and are therefore not considered acceptable as a stand-alone method of contraception in this study
11. Women of child-bearing potential who are not currently sexually active must agree to use a medically accepted method of contraception should they become sexually active while participating in the study. Post-menopausal women (having had no menses for ≥24 months) are exempted from the requirement for use of contraception
12. A subject must be willing to initiate CD4+ cell count-guided chemoprophylaxis to prevent opportunistic infection |
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E.4 | Principal exclusion criteria |
1) Subjects must not have detectable CXCR4-tropic or dual/mixed CCR5/CXCR4-tropic HIV isolates at Screening (i.e. HIV isolate must be solely CCR5-tropic)
2) Subjects must not have any condition that, in the opinion of the investigator, is likely to increase the risk of seizures
3) Subjects must not have a prior history of malignancy (with the exceptions of surgically resected basal-cell carcinoma or cutaneous Kaposi's sarcoma without visceral or mucosal inlvolement that resolved without systemic anticancer treatment) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportions of subjects with undetectable plasma HIV-1 RNA (<50 copies/mL by Ultrasensitive Amplicor HIV-1 Monitor Test, version 1.5) at 48 weeks will be compared to between vicriviroc and control groups as the primary measure of antiviral efficacy. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |