E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Human Immunodeficiency Virus (HIV-1) Infection |
Infección por el Virus de la Inmunodeficiencia Humana (VIH-1) |
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E.1.1.1 | Medical condition in easily understood language |
Human Immunodeficiency Virus (HIV-1) Infection |
Infección por el Virus de la Inmunodeficiencia Humana (VIH-1) |
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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 |
Caracterizar la eficacia virológica del cambio de E/C/F/TAF CDF o pauta que contiene TDF a B/F/TAF CDF en pacientes virológicamente suprimidos, definida por el ARN del VIH-1 <50 copias/ml en la semana 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 - To characterize the virologic efficacy of switching to B/F/TAF FDC defined by HIV-1 RNA <50 copies/mL at Week 48 |
- Caracterizar la seguridad y tolerabilidad del cambio a B/F/TAF CDF desde E/C/F/TAF CDF o pauta que contiene TDF. - Caracterizar la eficacia virológica del cambio a B/F/TAF CDF definida por el ARN del VIH-1 <50 copias/ml en la semana 48. |
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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 |
Los sujetos deben cumplir todos los criterios de inclusión siguientes para ser considerados aptos para su participación en este estudio. 1) Tener capacidad para comprender y firmar un formulario de consentimiento informado, que debe obtenerse antes de iniciar los procedimientos del estudio. 2) Tener ≥ 65 años de edad. 3) Estar recibiendo actualmente una pauta antirretroviral de CDF de E/C/F/TAF (o FTC/TDF + un tercer fármaco si participa actualmente o ha participado previamente en el GS-US-292-1826) durante ≥ 3 meses. 4) ARN del VIH-1 en plasma documentado < 50 copias/ml durante el tratamiento con E/C/F/TAF (o FTC/TDF + tercer fármaco si está participando actualmente o participó previamente en el GS-US-292-1826) durante las 2 visitas previas a la visita de selección (o nivel de ARN del VIH-1 indetectable de acuerdo con el análisis local que se esté utilizando si el límite de detección es ≥ 50 copias/ml) a) Son aceptables las elevaciones virológicas no confirmadas de ≥ 50 copias/ml, pero < 400 copias/ml (viremia detectable temporal, o "blip") en el pasado. b) Si el límite inferior de detección del análisis local de ARN del VIH-1 es < 50 copias/ml (p. ej., < 20 copias/ml), el nivel de ARN del VIH-1 en plasma no puede exceder 50 copias/ml en dos análisis de ARN del VIH-1 consecutivas después de haber alcanzado < 50 copias/ml. 5) Niveles plasmáticos de ARN del VIH-1 < 50 copias/ml en la visita de selección. 6) No tener sospecha de resistencia o resistencia documentada a FTC, TFV o BIC incluida, entre otras, aquella a las mutaciones K65R y M184V/I de la transcriptasa inversa. 7) ECG normal (o, si es anormal, determinado como no clínicamente significativo por el investigador) 8) Función renal adecuada: TFGe ≥ 30 ml/min según la fórmula Cockcroft-Gault para el aclaramiento de la creatinina. 9) Los sujetos fértiles de sexo masculino que mantengan relaciones heterosexuales con mujeres en edad fértil deben aceptar utilizar uno o varios métodos anticonceptivos especificados en el protocolo. 10) Los sujetos de sexo masculino deben aceptar abstenerse de donar esperma desde la primera dosis de fármaco del estudio hasta después del final de la exposición sistémica relevante. 11) Esperanza de vida > 1 año. |
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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 |
No se inscribirá en este estudio a los sujetos que cumplan cualquiera de los siguientes criterios de exclusión: 1) Una enfermedad oportunista indicativa de VIH en estadio 3 diagnosticada dentro de los 30 días previos a la selección. 2) Sujetos que experimenten cirrosis descompensada (p. ej., ascitis, encefalopatía o varices hemorrágicas). 3) Haber sido tratado con tratamientos inmunosupresores o agentes quimioterapéuticos dentro de los 3 meses previos a la selección del estudio, o que esperen recibir estos agentes o esteroides sistémicos (p. ej., dosis de prednisona > 10 mg al día o equivalente) durante el estudio (p. ej., corticoesteroides, inmunoglobulinas y otras terapias inmunológicas o basadas en citocinas). 4) Consumo en la actualidad de alcohol o sustancias que el investigador estima podrían interferir con el cumplimiento del estudio por parte del paciente. 5) Neoplasia maligna dentro de los 5 años previos de la selección distinta de sarcoma de Kaposi cutáneo, cáncer de piel no melanoma completamente resecado (carcinoma de células basales o carcinoma escamoso cutáneo no invasivo), o carcinoma in situ de cervix (CIN 3) o del ano completamente resecado (AIN 3). Se permite una neoplasia maligna anterior tratada con un tratamiento curativo y para la que no ha habido evidencia de enfermedad durante los últimos cinco años previos a la selección. 6) Infecciones graves, activas (aparte de la infección por VIH-1) que requieran tratamiento antibiótico o antifúngico parenteral dentro de los 30 días previos al día 1. 7) Participación en cualquier otro ensayo clínico, incluidos estudios observacionales, sin la aprobación previa del supervisor médico. 8) Cualquier otra afección o tratamiento previo que, en opinión del investigador, haría que el sujeto no fuera apto para el estudio o no pudiera cumplir con los requisitos posológicos. 9) Hipersensibilidad conocida a comprimidos de CDF de B/F/TAF, sus metabolitos o a los excipientes de formulación. 10) Sujetos que reciben tratamiento continuado con cualquiera de los medicamentos recogidos en el protocolo, incluidos fármacos que no se vayan a usar con BIC, FTC y TAF. 11) Hepatitis aguda en los 30 días previos a la entrada en el estudio. 12) Infección activa por tuberculosis. |
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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 |
ARN del VIH-1 <50 copias/ml en la semana 24 - definido por el algoritmo snapshot de la Food and Drug Administration (FDA) |
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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 - HIV-1 RNA <50 copies/mL at Week 48 - defined by the Food and Drug Administration (FDA) snapshot algorithm |
- Acontecimientos adversos a la semana 24 - Acontecimientos adversos a la semana 48 - RNA del VIH-1 <50 copias/ml en la semana 48 - definido por el algoritmo snapshot de la Food and Drug Administration (FDA) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 24 and Week 48 |
Semana 24 y semana 48 |
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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 |
Resultados informados del paciente |
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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 | 9 |
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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LVLS |
Última visita del último paciente |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |