| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 evaluate the efficacy of DTG/3TC for the maintenance of virological suppression in
adults with HIV infection compare to BIC/FTC/TAF and to show non inferiority of
DTG/3TC versus BIC/FTC/TAF for the maintenance of virological suppression in adults
with HIV at 48 weeks. The study could allow claiming for superiority. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy of DTG/3TC for the maintenance of virological suppression compare to BIC/FTC/TAF. - To evaluate changes in weight and BMI from baseline.
- To assess absolute values and changes from baseline in CD4+ cells count and CD4:CD8 ratio - To assess changes in total and regional fat and fat-free mass.
- To assess changes in subcutaneous and visceral fat. - To assess changes in lumbar and hip bone mineral density and trabecular bone score. - To assess changes in fasting glucose, insulin, HOMA-IR, HbA1c, plasma lipids, and FIB- 4 score. - To assess changes in estimated glomerular filtration rate (CKD-EPI) and urinary protein/creatinine with both therapies at week 48 and 96. - To assess changes in blood pressure at 48 and 96 weeks. - To evaluate changes in sleep quality, anxiety and depression and quality of life at each visit. - To evaluate tolerability of DTG/3TC and BIC/FTC/TAF. - To assess genotypic resistance mutations, in case of viral failure. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Omics sub-study, version 3.0 date 27nov2020. Objective: To gain insight on the mechanistic pathways involved on weight changes associated with
switching to BIC/FTC/TAF vs. DTG/3TC.
These studies will be targeted at least to inflammation, insulin resistance, and other weightrelated
metabolic consequences (obesity).
2. Senescence sub-study, version 3.0 date 27nov2020. Objective: This study will explore the impact of the two treatment arms (BIC/FTC/TAF Vs DTG/3TC) in
CD4 and CD8 T-cell TL, ROS and phosphorylated p53 levels, antioxidant mechanisms and
EAA. We believe that participants included into the BIC/FTC/TAF arm treatment could have a
shorter TL in CD4, CD8 T cell than non-TAF treated participants and both treatment arms could
reveal similar levels of ROS, phosphorylated p53, SODs and catalase mRNAs and EAA.
3. Fat biopsies sub-study, version 3.0 date 27nov2020. Objective:To assess potential effects of switching to BIC/FTC/TAF vs. DTG/3TC on expression of marker
genes of mitochondrial function, adipogenesis, and inflammation in subcutaneous fat tissue.
Assays on adipose tissue gene expression will be complemented by analysis in serum of
adipokines representative of adipose tissue function (leptin, adiponectin) using specific ELISAs,
and inflammation biomarkers (TNFalpha, MCP-1, IL-6, IL-8, IL-10, IL-18) using Multiplex
analysis. |
|
| E.3 | Principal inclusion criteria |
1. Understanding the study information provided and being capable of giving written informed consent
2. Confirmed HIV infection.
3. ≥18 years of age on the day of screening.
4. HIV RNA <50 copies/mL for at least 24 weeks before screening.
5. Receiving any regimen for HIV containing more than 1 pill a day or any single tablet regimen containing at least one of the following: cobicistat-boosting, efavirenz, or tenofovir disoproxyl fumarate for at least 24 weeks before screening. Patients with TAF are expected from cobiscitat-boosting single tablet regimens containing darunavir or elvitegravir and from morethan-1-pill-a-day regimens containing TAF/FTC; their participation will be limited to ≤25%. Patients will be stratified according to the presence or not of TAF in their regimens, as well as according to gender.
6. No evidence of previous viral failure (see appendix 4).
7. No known or suspected resistance to study drugs (see appendix 4).
8. Females of childbearing potential, must be using highly effective methods of contraception from study inclusion and at least 4 weeks after last study visit; all female volunteers must be willing to
undergo urine pregnancy testing at the time points specified in the schedules of events.
9. Clinical stability: Participants who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history,
laboratory tests, and cardiac monitoring.
At least 33% of the patients included will be women. We will also endeavour
to recruit as many non-Caucasian participants as possible. |
|
| E.4 | Principal exclusion criteria |
1. Is pregnant or lactating at the screening visit or at any time during the study or is planning on becoming pregnant over the duration of the study.
2. Evidence of Hepatitis B virus infection based on at least one positive result of testing at Screening for Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (anti-HBc)
3. Previous or current therapy with dolutegravir or bictegravir.
4. History of allergy to study drugs or their components.
5. Liver disease as defined by ALT≥5xULN or ALT≥3xULN and Bili
≥1.5xULN (with >35% direct bilirubin).
6. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary
abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones);
7. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification and/or anticipated need for Hep C treatment.
8. Kidney disease as defined by CKD-EPI <50ml/min.
9. Any recently (<=6 months) diagnosed clinical condition or recently (<=6 months) initiated concomitant therapy that may primarily affect weight or body composition. E.g., including but not limited to endocrine disorders, osteoporosis or medications to treat these clinical conditions, with the exception of controlled diabetes mellitus. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL (FDA Snapshot, 4% noninferiority
margin) at 48 weeks. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL (FDA Snapshot, 4% noninferiority margin) at 96 weeks.
- Proportion of patients with plasma HIV-1 RNA <50 copies/mL (FDA Snapshot) at 48 and 96 weeks.
-Absolute weight and BMI change and proportion of patients with weight change >5% from baseline at 48 and 96 weeks.
- Absolute values and changes from baseline in CD4+ cells count and CD4:CD8 ratio at 48 and 96 weeks.
- Change in total and regional (trunk and extremities) fat by DXA at 48 and 96 weeks.
- Change in total and regional (trunk and extremities) fat-free mass by DXA at 48 and 96 weeks.
- Change in lumbar and hip bone mineral density (BMD) and trabecular bone score (TBS) by DXA at 48 and 96 weeks.
- Change in subcutaneous and visceral fat (CT) at 48 and 96 weeks. Single-slice L2-L3 abdominal CT scan when breath hold.
- Change in fasting glucose, insulin, HOMA-IR, HbA1c, plasma lipids (total, HDL, and LDL cholesterol, triglycerides), and FIB-4 score at 48 and 96 weeks.
- Changes in estimated glomerular filtration rate (CKD-EPI) and urinary protein/creatinine
- Change in blood pressure at 48 and 96 weeks.
- Change in sleep quality (Pittsburg Sleep Quality Index) , anxiety and depression (HAD), and
quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM)) at each visit.
- Incidence and severity of adverse events (clinical and laboratory) and incidence of adverse events leading to treatment discontinuation.
- Incidence of genotypic resistance mutations in participants with virological failure at weeks 48
and 96. |
|
| 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 | Yes |
| 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 | 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 | 550 |
| 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 | 25 |
| 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
|
| LPLV |
| Ultima visita del último paciente |
|
| 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 | 2 |
| E.8.9.1 | In the Member State concerned days | |
Print
