Clinical trial NCT04884139: DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV:
Official title: DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV: an Open-label Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1-infection
Lead sponsor: Fundacion SEIMC-GESIDA
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
First posted: 2021-05-12
Enrollment: 554
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The hypothesize that DTG/3TC will be non-inferior to BIC/FTC/TAF with a 4% margin in virologically suppressed HIV-infected patients. The study will allow claiming for Superiority. Assuming that both DTG and BIC may lead to similar weight gains (approximately 1 kg after 48 weeks) in virologically suppressed HIV-infected patients and that TAF may induce a further weight gain (approximately 1 kg after 48 weeks), also hypothesize that switching to BIC/FTC/TAF may lead to greater weight gain than switching to DTG/3TC over 48 weeks.

This trial is a Phase IV, open-label, randomized multicentre clinical trial evaluating the efficacy of DTG/3TC versus BIC/FTC/TAF for the maintenance of virological suppression in HIV patients.

Detailed description: Participants will be randomly assigned in a 1:1 ratio to receive DTG/3TC or BIC/FTC/TAF. Randomization will be stratified by sex and TAF use at baseline. At least 33% of the patients included will be women.

The investigator will also endeavour to recruit as many non-Caucasian participants as possible.

Patients with TAF-containing regimens at baseline will be limited to 25% or less of the total number of participants.

Three sub-studies will be performed: Omics sub-study ; Senescence sub-study; Fat biopsies sub-study.

Omics sub-study: Assess the mechanistic pathways involved on weight changes associated with switching to BIC/FTC/TAF vs. DTG/3TC.

Senescence sub-study: Assess the potential effects on the telomere length, epigenetic age and oxidative stress markers of switching to BIC/FTC/TAF vs. DTG/3TC.

Fat biopsies sub-study: 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), and inflammation biomarkers (TNFalpha, MCP-1, IL-6, IL-8, IL-10, IL-18).

Eligibility criteria: 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 \&lt;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 screeningPatients with TAF are expected from cobiscitat-boosting single tablet regimens containing darunavir or elvitegravir and from more-than-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.
6. No evidence of previous viral failure.
7. No known or suspected resistance to study drugs.
8. Females of childbearing potential, must be using highly effective methods of contraception from study inclusion and for 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.

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 \&gt;= 5x ULN or ALT \&gt;=3xULN and Bili =1.5xULN (with \&gt;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\&#39;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 \&lt;50ml/min.
9. Any recently (\&lt;=6 months) diagnosed clinical condition or recently (\&lt;=6 months) initiated concomitant therapy (see Section 6.5) 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 ontrolled diabetes mellitus.

Primary outcomes:
measure: Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL
timeFrame: Week 48
Secondary outcomes:
measure: Proportion of patients with plasma HIV-1 RNA ≥50 copies/mL
timeFrame: week 96
measure: Proportion of patients with plasma HIV-1 RNA <50 copies/mL
timeFrame: Week 48 and week 96
measure: Absolute weight
timeFrame: Basal, week 48 y week 96
measure: BMI change
timeFrame: Basal, week 48 y week 96
measure: Proportion of patients with weight change >5%
timeFrame: Basal, week 48 y week 96
measure: Absolute values in CD4+ cells count
timeFrame: Basal, week 48 y week 96
measure: Changes in CD4+ cells count
timeFrame: Basal, week 48 y week 96
measure: Absolute values CD4:CD8 ratio
timeFrame: Basal, week 48 y week 96
measure: Changes CD4:CD8 ratio
timeFrame: Basal, week 48 y week 96
measure: Change in total and regional (trunk and extremities) fat by DXA
timeFrame: Basal, week 48 y week 96
measure: Change in total and regional (trunk and extremities) fat-free mass by DXA
timeFrame: Basal, week 48 y week 96
measure: Change in lumbar and hip bone mineral density (BMD) by DXA
timeFrame: Basal, week 48 y week 96
measure: Change trabecular bone score (TBS) by DXA
timeFrame: Basal, week 48 y week 96
measure: Change in subcutaneous and visceral fat (CT)
timeFrame: Basal, week 48 y week 96
measure: Change in fasting glucose cholesterol, triglycerides), and FIB-4 score
timeFrame: Basal, week 48 y week 96
measure: Change insulin cholesterol, triglycerides), and FIB-4 score
timeFrame: Basal, week 48 y week 96
measure: Change in HOMA-IR cholesterol, triglycerides), and FIB-4 score
timeFrame: Basal, week 48 y week 96
measure: Change in HbA1c cholesterol, triglycerides), and FIB-4 score
timeFrame: Basal, week 48 y week 96
measure: Change in plasma lipids (total, HDL, and LDL) cholesterol, triglycerides), and FIB-4 score
timeFrame: Basal, week 48 y week 96
measure: Changes in estimated glomerular filtration rate (CKD-EPI)
timeFrame: Basal, week 48 y week 96
measure: Changes in urinary protein/creatinine
timeFrame: Basal, week 48 y week 96
measure: Change in blood pressure
timeFrame: Basal, week 48 y week 96
measure: Change in sleep quality (Pittsburg Sleep Quality Index)
timeFrame: From basal, until week 96 , in each visit
measure: Change in anxiety and depression (HAD) quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM
timeFrame: From basal, until week 96 , in each visit
measure: Change in quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM)
timeFrame: From basal, until week 96 , in each visit
measure: Incidence and severity of adverse events (clinical and laboratory)
timeFrame: From basal, until week 96 , in each visit
measure: Incidence of adverse events leading to treatment discontinuation.
timeFrame: From basal, until week 96 , in each visit
measure: Incidence of genotypic resistance mutations in participants with virological failure
timeFrame: Week 48 and week 96
Other outcomes:
Locations:
city: Villajoyosa
country: Spain
facility: H. Marina Baixa
state: Alicante
city: Alcorcón
country: Spain
facility: Hospital Fundación Alcorcón
state: Madrid
city: Alicante
country: Spain
facility: H. General Universitario Dr. Balmis
city: Alicante
country: Spain
facility: H. de Elche
city: Almería
country: Spain
facility: H. de Torrecárdenas
city: Barcelona
country: Spain
facility: H. Clinic
city: Barcelona
country: Spain
facility: H. Germans Trias i Pujol
city: Barcelona
country: Spain
facility: H. de Bellvitge
city: Barcelona
country: Spain
facility: H. de Igualada
city: Barcelona
country: Spain
facility: H. del Mar
city: Barcelona
country: Spain
facility: H. San Joan de Deu
city: Barcelona
country: Spain
facility: H. Sant Creu y Sant Pau
city: Barcelona
country: Spain
facility: H. Vall de Hebron
city: Coruña
country: Spain
facility: CHUAC
city: Guadalajara
country: Spain
facility: H. Universitario de Guadalajara
city: Huelva
country: Spain
facility: H. Juan Ramón Jimenez
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: H. Infanta Leonor
city: Madrid
country: Spain
facility: H. La Princesa
city: Madrid
country: Spain
facility: H. Príncipe de Asturias
city: Madrid
country: Spain
facility: H. Univ. La Paz
city: Madrid
country: Spain
facility: H. Univ. Puerta de Hierro
city: Marbella
country: Spain
facility: H. Costa del Sol
city: Murcia
country: Spain
facility: H. Reina Sofía
city: Oviedo
country: Spain
facility: H. Central de Asturias
city: Palma De Mallorca
country: Spain
facility: H. Son Espases
city: Palma De Mallorca
country: Spain
facility: H. Son Llatzer
city: Sevilla
country: Spain
facility: H. de Valme
city: Tarragona
country: Spain
facility: H. Joan XXIII
city: Valencia
country: Spain
facility: H. Clínico Univ. de Valencia
city: Valladolid
country: Spain
facility: H Clinico Univ. de Valladolid
city: Vigo
country: Spain
facility: H. Alvaro Cunquerio
city: Zaragoza
country: Spain
facility: H. Clinico Univ. Lozano Bleza
Study officials:
affiliation: H. Clinc de Barcelona
name: Esteban Martinez, MD
role: PRINCIPAL_INVESTIGATOR
References: