| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV infection |
| Infección por el VIH |
|
| E.1.1.1 | Medical condition in easily understood language |
| HIV infection |
| Infección por el VIH |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020161 |
| E.1.2 | Term | HIV infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| 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 assess changes in weight after switching from Triumeq® to Rezolsta® plus Kivexa® or to Symtuza® in those HIV-infected people who presented weight gain during the dolutegravir-based regimen. |
| Evaluar los cambios en el peso después de cambiar de Triumeq® a Rezolsta® más Kivexa® o a Symtuza® en aquellos sujetos con infección por el VIH que presentaron aumento de peso durante el tratamiento con un régimen que contiene dolutegravir. |
|
| E.2.2 | Secondary objectives of the trial |
To assess the mechanisms of weight gain associated with dolutegravir by changes in:
- Body mass index.
- Total body composition measured by DEXA scan.
- Waist-to-hip ratio.
- Different abdominal fat layers measured by ultrasound.
- Lipid and lipoprotein parameters in blood.
- HOMA-IR, adiponectin and leptin.
- Cytokines, and other hormonal parameters, depending on the region where abdominal fat changes are observed.
To assess the safety of the switch from Triumeq® to Rezolsta® and Kivexa® or Symtuza® by changes in virological and immunological parameters and incidence of adverse events and drug-related discontinuations. |
Evaluar los mecanismos de aumento de peso asociados a dolutegravir mediante los cambios en:
- Índice de masa corporal.
- Composición corporal total medida por escáner DEXA.
- Ratio cintura-cadera.
- Diferentes capas de tejido graso medidas por ecografía.
- Lípidos y lipoproteínas en sangre.
- HOMA-IR y, adiponectina y leptina.
- Citoquinas y otros parámetros hormonales, dependiendo de la región donde se observen cambios en las capas de tejido graso abdominal.
Evaluar la seguridad del cambio de Triumeq® a Rezolsta® más Kivexa® o a Symtuza® mediante los cambios en los parámetros virológicos e inmunológicos y la incidencia de acontecimientos adversos. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Adult ≥ 18 years old having a diagnosis of HIV-1 infection.
2. Current ARV therapy with Triumeq® started at least 6 months before baseline.
3. Evidence of gain weight ≥5% during treatment with Triumeq® not associated with any medical condition or change of habit.
4. Maintained undetectable plasma HIV-1 RNA (viral load < 50 copies/mL) for at least 12 months before baseline.
5. Voluntary written informed consent.
6. In women of childbearing potential, negative pregnancy test and commitment to use contraceptive method throughout the study.
7. Commitment to follow the study procedures and avoid starting activities that may result in weight gain/decrease during the study. |
1. Adulto ≥18 años con diagnóstico de infección por el VIH-1.
2. En tratamiento con Triumeq® desde al menos 6 meses antes de la visita basal.
3. Evidencia de aumento de peso ≥5% durante el tratamiento con Triumeq®, no asociada a ninguna condición médica o cambio de hábito.
4. Carga viral del VIH-1 en plasma indetectable mantenida (carga viral <50 copias/mL) desde al menos 12 meses antes de la visita basal.
5. Firma del consentimiento informado.
6. En mujeres con potencial de procreación, test de embarazo negativo y compromiso de utilizar un método anticonceptivo a lo largo del estudio
7. Compromiso para seguir los procedimientos del estudio y evitar el inicio de actividades que puedan resultar en un aumento/disminución del peso. |
|
| E.4 | Principal exclusion criteria |
1. Previous virological failure to protease inhibitors.
2. Suspected or documented resistance mutations to the protease, as well as NRTI–related mutations that may impact nucleoside activity.
3. Systemic concurrent process such as coinfection with hepatitis C or B, acute systemic infection within the last 4 months, neoplasm, chronic inflammatory process, or any other condition that could impair subject’s safety, according to investigator criteria.
4. Treatment with drugs or other conditions that induce an increase (corticosteroids, antidepressants and antipsychotics, stop smoking habit, etc) or decrease (amphetamine, antidiabetics, diet, etc) of body fat.
5. Pregnant or breastfeeding women. |
1. Fracaso virológico previo a inhibidores de la proteasa.
2. Sospecha o documento de mutaciones de resistencia a la proteasa, así como mutaciones relacionadas con NRTI que puedan impactar en la actividad de los nucleósidos.
3. Proceso intercurrente sistémico como infección de hepatitis C o B, infección aguda sistémica en los últimos 4 meses, neoplasia, proceso inflamatorio crónico, o cualquier otra condición que pueda poner en riesgo al sujeto, de acuerdo al criterio del investigador.
4. Tratamiento con medicamentos o otras condiciones que puedan producir un aumento (corticoesteroides, antidepresivos y antipsicóticos, haber dejado de fumar, …) o disminución (anfetaminas, antidiabéticos, dieta, …) de la masa grasa.
5. En mujeres, estar embarazada o en período de lactancia. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
To compare the percentage of individuals with a significant reduction in weight after 48 weeks between groups (Triumeq® versus Rezolsta® and Kivexa® or Symtuza®), and intragroup.
Significant reduction of weight will be defined as a decrease of ≥5% from study baseline weight.
Thus, the following categories for grouping individuals according to the reduction in weight will be used: <5%, 5-10%, or >10%. |
Comparar el porcentaje de indivíduos con reducción de peso significativa después de 48 semanas entre los grupos de tratamiento (Triumeq® versus Rezolsta® más Kivexa® o Symtuza®).
La reducción de peso significativa se definirá como una disminución del 5 % o más respecto al peso basal.
Además, se definirán las siguientes categorías para agrupar a los individuos de acuerdo a la reducción del peso: <5%, 5-10%, o >10%. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
To compare changes between groups (Triumeqâversus Rezolstaâ plus Kivexaâ or Symtuza®) and intragroup at week 48 from baseline in:
- BMI and percentage of individuals whose BMI changed from normal-overweigh- obesity or the reverse.
- Total body composition assessed by DEXA scan. According to a World Health Organization expert committee, ‘‘there is no agreement about cut-off points for the percentage of body fat that constitutes obesity’’. Thus, the following categories for grouping individuals according to the changes in whole-body percentage fat will be used: <5%, 5-10%, or >10%.
- Waist-to-hip ratio
- Percentage of individuals who change > 5% in whole-body percentage body fat calculated as total body fat mass divided by total mass (from DEXA) x 100.
- Abdominal fat layers [superficial and profound subcutaneous fat, preperitoneal fat, visceral (omental) fat and retroperitoneal (para and perirenal) fat] measured by ultrasound.
- Lipid and lipoprotein parameters.
- Lumbar spine (L2-L4) and femoral (total femur, trochanter, femoral neck) bone mass density (BMD) and T-scores.
- HOMA-IR, adiponectin and leptin
- Cytokines, and other hormonal parameters, depending on the region where abdominal fat changes are observed.
- Virological and immunological (CD4 and CD8 T cell counts) changes.
- Percentage of subjects with AE and ARV drug-related discontinuations. |
Comparar los cambios entre grupos de tratamiento (Triumeq® versus Rezolsta® más Kivexa® o Symtuza®) e intragrupo a semana 48 desde el basal de:
- IMC y porcentaje de individuos cuyo IMC haya cambiado de normal-sobrepeso-obesidad o viceversa.
- Composición corporal total evaluada por escáner DEXA. De acuerdo al Comité de Expertos de la Organización Mundial de la Salud “no hay un acuerdo para los puntos de corte para los porcentajes de grasa corporal que constituyen obesidad”. Se definirán las siguientes categorías para agrupar a los individuos de acuerdo a los cambios en el porcentaje de grasa corporal: <5%, 5-10%, o >10%.
- Ratio cintura-cadera.
- Porcentaje de individuos que cambian >5% en el porcentaje de grasa corporal.
- Capas de tejido graso abdominal [grasa subcutánea superficial y profunda, grasa preperitoneal, grasa visceral (omental) y grasa retroperitoneal (para y perirrenal)] medida por ecografía.
- Lípidos y lipoproteínas en sangre.
- Densidad minera ósea y T-scores de la espina lumbar (L2-L4) y femoral (fémur total, trocánter, cuello femoral)
- HOMA-IR, adiponectina y leptina.
- Citoquinas y otros parámetros hormonales, dependiendo de la región donde se observen cambios en las capas de tejido graso abdominal.
- Cambios en parámetros virológicos e inmunológicos (recuento de CD4 y CD8).
- Porcentaje de sujetos con AA y discontinuación de tratamiento relacionada con el medicamento. |
|
| 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 | No |
| 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 |
| Changes in weight. |
| Cambios en el peso. |
|
| 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 | 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 | 3 |
| 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 | 3 |
| 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
|
| Last subject last visit. |
| Última visita del último sujeto. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 21 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 21 |
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