E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020192 |
E.1.2 | Term | HIV-1 |
E.1.2 | System Organ Class | 100000004862 |
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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 |
The primary objective is to demonstrate non-inferiority in terms of the percentage of subjects who have plasma HIV-1 RNA levels <50 copies/mL after 48 weeks of follow-up after switching to DRV/rtv monotherapy versus triple therapy containing DRV/rtv (FDA Snapshot method). |
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E.2.2 | Secondary objectives of the trial |
1. the correlation of plasma HIV-1 RNA, cerebrospinal fluid (CSF) HIV-1 RNA, and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at week 48
2. change in neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks
3. the rate of plasma HIV-1 RNA suppression after 48 and 96 weeks of follow-up to DRV/rtv monotherapy versus triple therapy containing DRV/rtv, using the time to loss of virologic response (TLOVR) method.
4. the correlation of plasma HIV-1 RNA and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv
at Weeks 48 and 96
5. the loss of treatment options as defined by treatment-emergent phenotypic drug resistance
6. the viral genotype of subjects
7. To evaluate and compare safety and tolerability |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
a lumbar puncture (extraction of cerebrospinal fluid [CSF] from the spinal canal) for laboratory testing (antiviral effectiveness, pharmacokinetic analysis, biochemistry and immune markers) and an additional blood sample for pharmacokinetic analysis (to measure the drug level in blood) will be taken. The study hypothesis is that, after 48 weeks of randomised treatment, DRV/rtv monotherapy is as effective as the triple therapy containing DRV/rtv plus plus 2 nucleoside analogues |
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E.3 | Principal inclusion criteria |
1. Have documented HIV-1 infection.
2. Be male or female aged 18 or over 18 years old.
3. Criterion deleted per amendment.
4. Criterion modified per amendment.
4.1 Currently be receiving HAART for at least 48 weeks.
5. Criterion modified per amendment.
5.1 Have at least 2 documented plasma HIV-1 RNA <50 copies/mL, and no HIV-1 RNA 50 or over 50 copies/mL in the 48 weeks prior to the screening visit.
6. Be taking the same ARV combination for at least 8 weeks before screening.
7. Have the preference, together with the physician, to change the current HAART regimen for reasons of simplification and/or toxicity (examples of toxicities include but are not limited to: CNS, gastrointestinal disturbances, jaundice, anemia, nausea, neuropathy, paresthesia, hyperlipidemia, glucose intolerance or diabetes,
nephrolithiasis, lipodystrophy, hepatotoxicity, rash and skin related events, any other AE or intolerability or laboratory abnormalities caused by current HAART).
8. Criterion modified per amendment.
8.1 Have no CD4+ cell counts below 100 cells/mm3, from the time of first known HIV infection to the start of HAART, and >200 cells/mm3 at screening or a maximum of 4 weeks prior to screening.
9. Be able to comply with the protocol requirements. In particular, subjects should be willing to be followed up to Week 96 even if they discontinue randomized treatment.
10. If heterosexually active, a female of childbearing potential and a non-vasectomized male subject who has a female partner of childbearing potential must agree to use effective contraceptives from screening onwards until 30 days after completion of study treatment.
11. If a woman of childbearing potential, she must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening; and a negative serum or urine pregnancy test before the first dose of study medication to ensure they are not pregnant at the time of starting treatment.
12. Criterion modified per amendment.
12.1 Have voluntarily signed and dated an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. |
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E.4 | Principal exclusion criteria |
1. Criterion modified per amendment.
1.1 Has a history of virologic failure defined as 2 consecutive plasma HIV-1 RNA >500 copies/mL after initial viral suppression while on previous or current antiretroviral therapy.
2. Has a history of any primary PI mutations as defined by the IAS-USA guidelines 2010.24
3. Has clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency).
4. Is diagnosed with acute viral hepatitis at screening or before Baseline 1.
5. Is co-infected with hepatitis B.
6. Has documented hepatic cirrhosis.
7. Has a grade 3 or 4 laboratory abnormality as defined by the Division of AIDS (DAIDS) grading table (see Attachment 1: DAIDS AE grading table), with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:
* Subjects with pre-existing diabetes or with asymptomatic glucose grade 3 or 4 elevations.
* Subjects with asymptomatic triglyceride or cholesterol elevations of grade 3 or 4.
* Subjects taking atazanavir with asymptomatic hyperbilirubinemia of grade 3 or 4.
8. Has presence of any currently active AIDS defining illness (Category C conditions according to the Centers for Disease Control (CDC) Classification System for HIV Infection 1993) with the following exceptions:
* Stable cutaneous Kaposi's Sarcoma (ie, no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study.
* Wasting syndrome due to HIV infection.
9. Is a woman who is pregnant or breastfeeding.
10. Is an active drug abuser, including alcohol or recreational drugs.
11. Has any active clinically significant disease (eg, tuberculosis, cardiac dysfunction, pancreatitis, acute viral infections) or life threatening disease or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.
12. Has any medical or psychiatric condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the study protocol.
13. Is on anti-psychotic drugs.
14. Criterion modified per amendment.
14.1 Has a severe depression (based on test results from the BDI:
scoring between 30 and 63).
15. Has previously demonstrated clinically significant allergy or
hypersensitivity to any of the excipients of the investigational
medication (DRV).
16. Is hypersensitive to ritonavir or to any of the other ingredients found
in the ritonavir tablet.
17. Uses disallowed concomitant therapy (see Section 8 and DRV
Summary of Product Characteristics [SPC]25).
18. Is currently enrolled in an investigational drug study or has
participated in such study within 30 days before screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
the percentage of patients who have
plasma human immunodeficiency virus type-1 (HIV-1) ribonucleic acid (RNA) levels <50 copies/mL after 48 weeks of follow-up after switching to DRV/ritonavir (rtv) monotherapy versus triple therapy containing DRV/rtv
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
the correlation of plasma HIV-1 RNA, cerebrospinal fluid (CSF) HIV-1 RNA, and
neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at
week 48
change in neurocognitive function of DRV/rtv monotherapy versus
triple therapy containing DRV/rtv over 48 and 96 weeks
the rate of plasma HIV-1 RNA suppression after 48 and 96 weeks of follow-up to DRV/rtv monotherapy versus triple therapy containing DRV/rtv, using the time to loss of virologic response (TLOVR) method.
the correlation of plasma HIV-1 RNA and neurocognitive function of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96
the loss of treatment options of DRV/rtv monotherapy versus triple therapy containing DRV/rtv at Weeks 48 and 96, as defined by treatment-emergent phenotypic drug resistance
the viral genotype of subjects treated with DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks
To evaluate and compare safety and tolerability of DRV/rtv monotherapy versus triple therapy containing DRV/rtv over 48 and 96 weeks |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
monotherapy vs triple combination therapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | No |
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 | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |