| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Human Immunodeficiency Virus |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
| 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 | 10008919 |
| E.1.2 | Term | Chronic HIV 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 |
| Switching HIV-positive individuals whose virus has selected drug resistance associated mutations and are virologically suppressed (this means the drugs are still working and HIV is under the level of detection in the blood) on a boosted protease inhibitor-based antiretroviral drug regimen to Biktarvy [bictegravir (B)/emtricitabine (F)/tenofovir alafenamide] (TAF) single tablet regimen will maintain virological efficacy (HIV-1 RNA <50 copies/mL) over 24 weeks. |
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| E.2.2 | Secondary objectives of the trial |
• To estimate proportion of patients with HIV-1 RNA <50 copies/mL at week 48 using pure virological response (PVR)
• To estimate proportion of patients with HIV-1 RNA <50 copies/mL at weeks 24 and 48 using PVR in those with any archived resistance detected in proviral DNA
• To evaluate the emergence of new resistance mutations in participants with two consecutive viral load ≥50 copies/mL measured 2-3 weeks apart.
• To determine the safety and tolerability of B/F/TAF single tablet regimen in participants switching from boosted Protease Inhibitor-based regimens over 48 weeks
• To evaluate the between group change from baseline in patient reported outcomes at weeks 24 and 48
• To estimate the between group mean percentage change from baseline in serum lipid concentrations at weeks 24 and 48
• To estimate the between arm mean percentage change from baseline in HBA1c at weeks 24 and 48
• To estimate the between arm mean percentage change from baseline in weight and BMI at weeks 2 |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
18 years and above
Any nadir CD4 count and baseline VL
On a bPI-based ART regimen with at least one documented HIV-1 RNA <50 copies/mL within the previous 6 months and at screening
Eligible drug resistance mutations in historical genotype include the following:
o M184V/I with or without any nucleoside analogue mutation (e.g. L74I/V, Y115F, K70E/G/Q/T/N/S)
o M184V/I alone
o Up to 2 TAMs (M41L, D67N, K70R, L210W, T215F/Y, or K219Q/E/N/R) with or without M184V/I
o Any of the above with or without NNRTI mutations
No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI)
No known INSTI mutations
Must have historical genotype
Estimated GFR ≥ 50 mL/min (Cockcroft-Gault formula)
Have the following laboratory values at screening within 30 days prior to baseline
a) Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN)
b) AST and ALT ≤ 5.0 x ULN
c) Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male).
Provides written, informed consent to participate
Is willing to comply with the protocol requirements
If female and of child bearing potential, is using effective birth control methods (as agreed by the investigator) and willing to continue practicing these birth control measures during the trial and for at least 30 days after the end of the trial.
If male, and sexually-active with female partners of child bearing potential, is using effective barrier contraception, and willing to continue using this during the trial and for at least 30 days after the end of the trial.
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| E.4 | Principal exclusion criteria |
Exclusion under drug resistance mutations include:
o Presence of any of the following mutations: K65R/N/E
o Presence of multidrug resistance mutations: T69ins, Q151M with or without A62V, V75I, F77L, F116Y
o three or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, or K219Q/E/N/R)
Individuals experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
An opportunistic illness within the 30 days prior to screening
Active tuberculosis infection
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 (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine based therapies)
Current alcohol or substance use judged by the Investigator to potentially interfere with subjects’ adherence to study procedure.
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. Individuals 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
Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 (except if the parenteral therapy is for syphilis infection)
Any other clinical condition or prior therapy that will, in the opinion of the investigator, make the subject ineligible
Any known allergies to the excipients of B/F/TAF FDC
Females who are pregnant (as confirmed by positive urine pregnancy test)
Females who are breastfeeding
Women of child bearing age not using any reliable form of contraception (e.g. intrauterine device/intrauterine system, long-acting contraceptive injection, in addition to barrier methods)
Acute hepatitis in the 30 days prior to study entry, anyone with HCV who is likely to need direct acting antivirals in study
Any concomitant medications that cannot be administered with TAF (i.e strong inducers of p-glycoprotein) or bictegravir (dofetilide, rifampins)
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportions of individuals with HIV RNA <50 copies/mL at 24 weeks will be estimated using pure virologic response (PVR).
The percentage of participants with PVR for HIV-1 RNA cut-off at 50 copies/mL at Week 24 will be summarized.
PVR will be assessed as follows:
• On study treatment
• No confirmed virologic rebound defined as:
o HIV RNA ≥ 50 copies/mL on 2 consecutive visits
o HIV-1 RNA ≥ 50 copies/mL during study followed by premature discontinuation
Discontinuation prior to week 24 for reasons other than virologic rebound (i.e. no data in window and last HIV RNA < 50 copies/mL) are considered PVR
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
To estimate proportion of patients with HIV-1 RNA <50 copies/mL at week 48 using pure virological response (PVR)
To estimate proportion of patients with HIV-1 RNA <50 copies/mL at weeks 24 and 48 using PVR in those with any archived resistance detected in proviral DNA
To evaluate the emergence of new resistance mutations in participants with two consecutive viral load ≥50 copies/mL measured 2-3 weeks apart.
To determine the safety and tolerability of B/F/TAF single tablet regimen in participants switching from boosted Protease Inhibitor-based regimens over 48 weeks
To evaluate the between group change from baseline in patient reported outcomes at weeks 24 and 48
To estimate the between group mean percentage change from baseline in serum lipid concentrations at weeks 24 and 48
To estimate the between arm mean percentage change from baseline in HBA1c at weeks 24 and 48
To estimate the between arm mean percentage change from baseline in weight and BMI at weeks 24 and 48 |
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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 | 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.3.1 | Comparator description |
| Standard of care on a boosted Protease Inhibitor |
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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 | 7 |
| E.8.5 | The trial involves multiple Member States | No |
| 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 | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 1 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 1 |
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