| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV infected individuals |
| Individuos infectados por VIH |
|
| E.1.1.1 | Medical condition in easily understood language |
| HIV infected individuals |
| Individuos infectados por VIH |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| 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 determine Cabotegravir and Rilpivirine concentrations in seminal plasma, rectal tissue and cervicovaginal fluid (CVF) in male and female individuals living with HIV receiving IM Cabotegravir and Rilpivirine LA every 2 months. |
| - Determinar las concentraciones de Cabotegravir y Rilpivirina en semen, fluido rectal y fluido cervicovaginal en hombres y mujeres que viven con VIH recibiendo Cabotegravir y Rilpivirina LA intramuscular cada dos meses. |
|
| E.2.2 | Secondary objectives of the trial |
| - To evaluate HIV-1 RNA suppression in seminal plasma, rectal fluid and CVF in male and female individuals living with HIV receiving IM Cabotegravir and Rilpivirine LA every 2 months. |
| Evaluar la supresión de ARN-VIH-1 en semen, fluido rectal y fluido cervicovaginal en hombres y mujeres que viven VIH recibiendo Cabotegravir y Rilpivirina LA intramuscular cada dos meses |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Asymptomatic, HIV-1 infected individuals ≥ 18 years of age.
2. Male and female HIV-1 infected adult patients receiving standard triple therapy with 2 NRTIs (tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine plus an non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an integrase inhibitor) or a dual therapy (Dolutegravir/Lamivudine or Dolutegravir/Rilpivirine) during at least 6 months.
3. Plasma HIV-1 RNA <50 copies/mL for at least 6 months at the Screening visit.
4. Signed and dated written informed consent prior to inclusion.
5. Female Subjects of Childbearing Potential* with a negative pregnancy test (validated and sensitive serum or urine b -human chorionic gonadotrophin [sensitivity <=25mIU/mL], at screening and baseline, must agree to use one of the following methods of contraception to avoid pregnancy:
o Complete abstinence from penile-vaginal intercourse from at least 2 weeks prior to administration of Investigational Product and during the study intervention period [See Note 2 below];
o Male partner sterilization confirmed prior to the female participant’s entry into the study, and provided this male is the sole partner for that participant
o A contraceptive method that is highly effective** (with a failure rate of <1% per year). |
1. Individuos asintomáticos infectados por el VIH-1 ≥ 18 años de edad.
2. Pacientes adultos infectados por el VIH-1, hombres y mujeres, que reciben triple terapia estándar con 2 NRTI (tenofovir disoproxilo fumarato/emtricitabina o abacavir/lamivudina más un inhibidor de la transcriptasa inversa no nucleósido, un inhibidor de la proteasa potenciado o un inhibidor de la integrasa) o una terapia dual (Dolutegravir/Lamivudina o Dolutegravir/Rilpivirina) durante al menos 6 meses.
3. ARN del VIH-1 en plasma <50 copias/ml durante al menos 6 meses previos de la visita de selección.
4. Consentimiento informado por escrito firmado y fechado antes de la inclusión.
5. Sujetos femeninos en edad fértil* con una prueba de embarazo negativa (gonadotrofina coriónica humana β-gonadotrofina humana validada y sensible en suero u orina [sensibilidad <=25mIU/mL], en la selección y al inicio del estudio, y deben aceptar usar uno de los siguientes métodos anticonceptivos para evitar el embarazo:
o Abstinencia total del coito pene-vagina desde al menos 2 semanas antes de la administración del Producto en investigación y durante el período de intervención del estudio
o Esterilización de la pareja masculina confirmada antes de la entrada de la participante femenina en el estudio, y siempre que este hombre sea la única pareja de esa participante
o Un método anticonceptivo que sea altamente efectivo (con una tasa de falla de <1% por año).
|
|
| E.4 | Principal exclusion criteria |
1. Evidence of hepatitis B virus infection based on results of testing at screening.
2. Severe hepatic impairment (Grade 3-4 liver fibrosis, or cirrhosis).
3. Individuals with chronic HCV infection who may be anticipated to need as new HCV therapy prior to the study endpoint.
4. Ongoing malignancy
5. Active opportunistic infection
6. Resistance to any of the ARV included in the study or history of virologic failure with risk of resistance selection to any of the study drugs.
7. Any verified Grade 4 laboratory abnormality
8. Alanine Aminotransferase (ALT) ≥5 × Upper Limit Normal (ULN) or ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin) over the last 6 months
9. Severe renal impairment (estimated creatine clearance <30 mL/min per 1.73m2 via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method).
10. Females who are pregnant or breastfeeding or planning to become pregnant during the study period.
11. Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the investigators, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
12. Any condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
13. History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.
14. Current or anticipated need for chronic anti-coagulation or hereditary coagulation and platelet disorders such as haemophilia or Von Willebrand Disease.
15. Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternative medication |
1. Evidencia de infección por el virus de la hepatitis B basada en los resultados de las pruebas de detección.
2. Insuficiencia hepática grave (grado 3-4 de fibrosis hepática o cirrosis).
3. Individuos con infección crónica por VHC que se puede anticipar que necesitarán una nueva terapia contra el VHC antes del punto final del estudio.
4. Neoplasia maligna en curso
5. Infección oportunista activa
6. Resistencia a alguno de los antirretrovirales incluidos en el estudio o antecedentes de fracaso virológico con riesgo de selección de resistencia a alguno de los fármacos del estudio.
7. Cualquier anormalidad de laboratorio de Grado 4 verificada
8. Alanina aminotransferasa (ALT) ≥5 × Límite superior normal (LSN) o ALT ≥3xULN y bilirrubina ≥1,5xULN (con >35 % de bilirrubina directa) durante los últimos 6 meses
9. Insuficiencia renal grave (depuración de creatina estimada <30 ml/min por 1,73 m2 a través del método de la Colaboración en Epidemiología y Enfermedad Renal Crónica (CKD-EPI)).
10. Mujeres que estén embarazadas o amamantando o planeando quedar embarazadas durante el período de estudio.
11. Cualquier condición física o mental preexistente (incluido el trastorno por uso de sustancias) que, en opinión de los investigadores, pueda interferir con la capacidad del participante para cumplir con el programa de dosificación y/o las evaluaciones del protocolo o que pueda comprometer la seguridad del partícipe.
12. Cualquier condición que, en opinión del investigador, pueda interferir con la absorción, distribución, metabolismo o excreción de los medicamentos del estudio o impedir que el participante reciba la medicación del estudio.
13. Historia o presencia de alergia o intolerancia a los medicamentos del estudio o sus componentes o medicamentos de su clase.
14. Necesidad actual o anticipada de anticoagulación crónica o coagulación hereditaria y trastornos plaquetarios como la hemofilia o la enfermedad de Von Willebrand.
15. Participantes que reciben cualquier medicamento prohibido y que no quieren o no pueden cambiar a un medicamento alternativo |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| - Total concentrations of Cabotegravir and Rilpivirine in seminal plasma and rectal tissue in male individuals; and in CVF in female individuals, 2 months after cabotegravir and rilpivirine LA IM dose (prior to next dose). |
| - Concentraciones totales de Cabotegravir y Rilpivirina en plasma seminal y fluido rectal en individuos masculinos; y en fluido cervicovaginal en mujeres, 2 meses después de la dosis intramuscular de cabotegravir y rilpivirina de acción prolongada (antes de la siguiente dosis). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Protein unbound fraction and estimated unbound concentrations of Cabotegravir and Rilpivirine in seminal plasma and rectal tissue in male individuals; and in CVF in female individuals, 2 months after cabotegravir and rilpivirine LA IM dose (prior to next dose).
- HIV-1 RNA in seminal plasma and rectal tissue in male individuals; and in CVF in female individuals, 2 months after cabotegravir and rilpivirine LA IM dose. |
- Fracción de proteínas no unidas y concentraciones no unidas estimadas de Cabotegravir y Rilpivirina en plasma seminal y fluido rectal en individuos masculinos; y en fluido cervicovaginal en mujeres, 2 meses después de la dosis intramuscular de cabotegravir y rilpivirina de acción prolongada (antes de la siguiente dosis).
- ARN del VIH-1 en plasma seminal y fluido rectal en individuos masculinos; y en fluido cervicovaginal en mujeres, 2 meses después de la dosis intramuscular de cabotegravir y rilpivirina de acción prolongada. |
|
| 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 | No |
| 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 |
|
| 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 | 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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.8.3 |
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 | 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | 0 |
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