| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus Type 1 |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 20.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10068341 |
| E.1.2 | Term | HIV-1 infection |
| E.1.2 | System Organ Class | 100000004862 |
|
| 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 noninferiority in efficacy of a D/C/F/TAF containing once-daily single-tablet regimen versus DRV/COBI FDC combined with FTC/TDF FDC in HIV-1 infected, ARV treatment-naïve adult subjects, as determined by the proportion of virologic responders defined as having HIV-1 RNA <50 copies/mL at Week 48 (FDA-defined snapshot analysis), with a maximum allowable difference of 10%. |
|
| E.2.2 | Secondary objectives of the trial |
*to evaluate superiority of a D/C/F/TAF once-daily single-tablet regimen vs DRV/COBI FDC combined with FTC/TDF FDC as determined by having HIV-1 RNA <50 copies/mL at Week 48 (FDA-defined snapshot analysis), in case noninferiority is established
*to evaluate the immunologic response (CD4+ cell count) of the 2 treatment arms through Week 48
*to evaluate long-term efficacy and safety of the D/C/F/TAF regimen (until Week 96 and beyond)
*to evaluate the incidence of grade 3 and 4 AEs, serious adverse events (SAEs), and premature discontinuations due to AEs in the 2 treatment arms through Week 48
*to evaluate the change from baseline in serum creatinine, eGFR based on creatinine clearance and eGFR based on cystatin C clearance in the 2 treatment arms at Week 48
*to evaluate the change from baseline in renal biomarkers at Week 48;
*to assess the development of viral resistance in the 2 treatment arms through Week 48;
*to evaluate the steady-state pharmacokinetics of DRV and TAF. |
|
| 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 bone investigation substudy will be performed at selected study sites, to assess bone biomarkers and dual energy x-ray absorptiometry (DXA) scans, in at least 170 subjects (85 subjects in each treatment arm) who provide informed consent for the substudy. To determine BMD of the hip and spine, consenting subjects will have DXA scans performed at the time points specified in the protocol. In subjects participating in the DXA substudy, blood will be collected for assessment of bone biomarkers at the time points specified in the protocol.
Objectives of the bone investigation substudy:
*to evaluate the safety in the 2 treatment arms as determined by the percentage change from baseline in hip and spine BMD at Week 48;
*to evaluate the change from baseline in bone biomarker levels at Week 48. |
|
| E.3 | Principal inclusion criteria |
- Subject must be antiretroviral (ARV) treatment-naive (never treated with an ARV including post-exposure prophylaxis and pre-exposure
prophylaxis); no prior use of any approved or experimental anti- human immunodeficiency virus (anti-HIV) drug for any length of time. Subjects treated with post-exposure prophylaxis and/or pre-exposure prophylaxis may be enrolled in the study if treatment stopped at least 30 days prior to Screening
- Screening plasma HIV-1 ribonucleic acid (RNA) level greater than or equal to >=1,000 copies per milliliter (copies/mL)
- Cluster of Differentiation 4+ (CD4+) cell count >50 cells/microliter (cells/mcL)
- Screening HIV-1 genotype report must show full sensitivity to DRV, TDF and FTC
- Screening eGFRcreatinine >=70 mL/min according to the Cockcroft-Gault formula for creatinine clearance |
|
| E.4 | Principal exclusion criteria |
- Subject has been diagnosed with a new acquired immunodeficiency syndrome (AIDS)-defining condition within the 30 days prior to screening
- Subject has proven or suspected acute hepatitis within 30 days prior to screening
- Subject is hepatitis C or hepatitis B positive
- Subject has a history of cirrhosis |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Percentage of Participants With Human Immunodeficiency Virus (HIV) -1 Ribonucleic Acid (RNA) Less Than (<) 50 Copies per Milliliter (copies/mL) defined by FDA Snapshot Approach |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1) Percentage of Participants With HIV-1 RNA Less Than (<) 50 Copies/mL by FDA Snapshot Approach
2) Percentage of Participants With HIV-1 RNA Less Than (<) 50 Copies/mL Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm
3) Change From Baseline in Cluster of Differentiation-4 (CD4+) Cell Count at Week 48 and 96
4) Percentage of Participants With Resistance to antiretrovirals (ARVs) and Type of Resistance in Participants with Virologic Failure
5) Change From Baseline in Serum Creatinine, eGlomerular Filteration Rate-Creatinine (eGFR Creatinine) and eGFR Cystatin C at Week 48 and 96
6) Percentage of Participants Experiencing Grade 3 and 4 Adverse Events (AEs), Serious
Adverse Events (SAEs), and Premature Discontinuations due to AEs
7) Change From Baseline in Renal Biomarkers at Week 48 and 96
8) Percent Change From Baseline in Spine and Hip Bone Mineral Density (BMD) at Weeks 24, 48 and 96 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) Week 96
2) Week 48 and 96
3) Baseline, Week 48 and 96
4) Up to Week 48 and 96
5) Baseline, Week 48 and 96
6) Up to Weeks 48 and 96
7) Baseline, Week 48 and 96
8) Baseline, Week 24, 48 and 96 |
|
| 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 | Yes |
| 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 | No |
| 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 | 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 | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| DRV/COBI FDC coadministered with FTC/TDF FDC |
|
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 62 |
| 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 |
| Belgium |
| Canada |
| France |
| Germany |
| Italy |
| Poland |
| Russian Federation |
| Spain |
| United Kingdom |
| United States |
|
| 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
|
| The study is considered completed with the last visit for the last subject participating in the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 8 |
| 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 | 9 |
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