| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus (HIV-1) Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| Human Immunodeficiency Virus (HIV-1) Infection |
|
| 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 |
| To evaluate the efficacy of switching from a regimen of either DTG and F/TAF or DTG and F/TDF to a FDC of B/F/TAF versus DTG+F/TAF in virologically suppressed HIV-1 infected subjects with or without ARV resistance as determined by the proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety and tolerability of the two treatment groups through Week 48 |
|
| 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 |
- Optional Pharmacogenomic Testing.
For subjects who agree to participate and provide their additional specific consent, two blood samples will be obtained for the extraction of deoxyribonucleic acid (DNA) for genomic testing and for other biomarker research such as HLA. These samples will be collected at Day 1.
- Optional HIV Experience Tracker Substudy
Subjects will be offered participation in a substudy to track symptoms associated with the HIV diagnosis. Subjects who provide consent to participate will be asked to provide symptom related information for one week, using a web-based diary called the HIV Experience Tracker. The subject will complete the HIV Experience Tracker daily in the evenings, for 7 consecutive days after each of the following visits: Screening, Weeks 4 and 48. |
|
| E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for participation in this
study.
1) The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
2) Age ≥ 18 years
3) Currently receiving an ARV regimen of DTG+F/TAF or DTG+F/TDF for the following minimum time periods:
a) ≥ 6 months (if there is documented or suspected NRTI resistance prior to the screening visit),
b) ≥ 3 months (if there is no documented or suspected NRTI resistance prior to the screening visit)
4) Documented plasma HIV-1 RNA < 50 copies/mL during treatment with DTG+F/TAF or DTG+F/TDF (for a minimum period of ≥ 6 or ≥ 3 months, as applicable) preceding the Screening Visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL)
5) Plasma HIV-1 RNA levels < 50 copies/mL at Screening Visit
6) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
7) Adequate renal function
8) No documented resistance to INSTIs or confirmed virologic failure (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving < 50 copies/mL while on an INSTI-containing regimen)
9) Eligible subjects with the following historical ARV resistance are permitted to enroll:
- Any NRTI resistance mutations
- Any non-nucleoside reverse transcriptase mutations
- Any protease inhibitor mutations
- Subjects with resistance to 2 or more classes of antiretrovirals must be reviewed by the Gilead Medical Monitor to confirm eligibility
10) Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
11) Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin
12) Adequate hematologic function
13) Serum amylase ≤ 5 × ULN (subjects with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
14) Male subjects who are fertile and females subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
15) Male subjects must agree to refrain from sperm donation from first study drug dose and throughout the study period
16) Life expectancy ≥ 1 year |
|
| E.4 | Principal exclusion criteria |
Subjects who meet any of the following exclusion criteria are not to be enrolled in this study.
1) An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening (refer to Appendix 5)
2) Subjects experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding)
3) Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during
the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
4) Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
5) A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous
squamous carcinoma. Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Day 1 and are not anticipated to require systemic therapy during the study
6) Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
7) Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
8) Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements
9) Known hypersensitivity to B/F/TAF FDC or DTG+F/TAF FDC tablets, their metabolites, or formulation excipient
10) Females who are pregnant (as confirmed by positive serum pregnancy test)
11) Females who are breastfeeding
12) Subjects receiving ongoing therapy with any of the medications listed in the protocol, including drugs not to be used with BIC, FTC, TAF, and DTG
13) Acute hepatitis in the 30 days prior to randomization
14) Active tuberculosis infection |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The proportion of subjects with HIV-1 RNA ≥ 50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- The proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm
- The change from baseline in CD4+ cell count at Week 48 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Patient reported outcomes |
|
| 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 | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| 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 |
| Austria |
| Canada |
| France |
| Germany |
| Puerto Rico |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 1 |
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