E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV-1) Infection |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus (HIV-1) Infection |
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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 | 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 |
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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 characterize the virologic efficacy of switching virologically suppressed subjects on an E/C/F/TAF FDC or TDF-containing regimen to B/F/TAF FDC defined by HIV-1 RNA <50 copies/mL at Week 24 |
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E.2.2 | Secondary objectives of the trial |
- To characterize the safety and tolerability of switching to B/F/TAF FDC from an E/C/F/TAF FDC or TDF-containing regimen through Week 96.
- To characterize the virologic efficacy of switching to B/F/TAF FDC defined by HIV-1 RNA <50 copies/mL at Week 48, Week 72 and Week 96. |
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E.2.3 | Trial contains a sub-study | No |
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 ≥ 65 years
3) Currently receiving an ARV regimen of E/C/F/TAF FDC (or FTC/TDF + 3rd agent if currently or previously participated in GS-US-292-1826) for ≥ 3 months
4) Documented plasma HIV-1 RNA < 50 copies/mL during treatment with E/C/F/TAF (or FTC/TDF + 3rd agent if currently or previously participated in GS-US-292-1826) for the last 2 visits 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)
a) Unconfirmed virologic elevations of ≥ 50 copies/mL but < 400 copies/mL (transient detectable viremia, or “blip”) in the past are acceptable.
b) If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL (eg, < 20 copies/mL), the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests after < 50 copies/mL has been achieved.
5) Plasma HIV-1 RNA levels < 50 copies/mL at Screening Visit
6) Have no documented or suspected resistance to FTC, TFV, or BIC including, but not limited, to the reverse transcriptase resistance mutations K65R and M184V/I
7) Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
8) Adequate renal function: eGFR ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance
9) Male subjects who are fertile and engage in heterosexual intercourse with women who are of child-bearing potential must agree to use protocol specified method(s) of contraception
10) Male subjects must agree to refrain from sperm donation from first study drug dose until after the end of relevant systemic exposure
11) Life expectancy >1 year
12) Hepatic transaminases (AST and ALT) ≤ 5 upper limit of normal (ULN)
13) Total bilirubin ≤ 1.5X ULN or normal direct bilirubin
14) Adequate hematologic function (absolute neutrophil count ≥ 750/mm3 (≥ 0.75 GI/L); platelets ≥ 50,000/mm3 (≥ 50 GI/L); hemoglobin ≥ 8.5 g/dL (≥ 85 g/L)) |
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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
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 (e.g. prednisone doses > 10 mg daily or equivalent) 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) Malignancy within 5 years of screening other than cutaneous Kaposi’s sarcoma, completely resected non-melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus
(AIN 3). A prior malignancy treated with curative therapy and for which there has been no evidence of disease for at least five years prior to screening is allowed.
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 Medical Monitor
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 tablets, their metabolites, or formulation excipient
10) Subjects receiving ongoing therapy with any of the medications listed in the protocol, including drugs not to be used with BIC, FTC, and TAF
11) Acute hepatitis in the 30 days prior to study entry
12) Active tuberculosis infection |
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E.5 End points |
E.5.1 | Primary end point(s) |
HIV-1 RNA <50 copies/mL at Week 24 - defined by the Food and Drug Administration (FDA) snapshot algorithm |
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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) |
- Adverse events through Week 24
- Adverse events through Week 48
- Adverse events through Week 72
- Adverse events through Week 96
- HIV-1 RNA <50 copies/mL at Week 48 - defined by the Food and Drug Administration (FDA) snapshot algorithm
- HIV-1 RNA <50 copies/mL at Week 72 - defined by the Food and Drug Administration (FDA) snapshot algorithm
- HIV-1 RNA <50 copies/mL at Week 96 - defined by the Food and Drug Administration (FDA) snapshot algorithm |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 24, Week 48, Week 72 and Week 96. |
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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 |
Patient reported outcomes |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 31 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 3 |
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 | 3 |