DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV:

HIV-1-infection Clinical Trial

— PASO-DOBLE  

Official title:

DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV: an Open-label Randomized Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04884139
• Other study ID #: GESIDA11720
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: July 14, 2021
• Est. completion date: January 1, 2025

Study information

• Verified date: August 2023
• Source: Fundacion SEIMC-GESIDA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 investigatora 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 555
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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 >= 5x ULN 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 (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 controlled diabetes mellitus.

Related Conditions & MeSH terms

• HIV-1-infection

Intervention

Drug:
• Dolutegravir/Lamivudine as a single pill
- Dose: Dolutegravir 50mg/ Lamivudine 300 mg -Route of adminstration: oral -Schedule of administration: once a day for 96 weeks.
• Bictegravir/Emtricitabine/Tenofovir alfenamide as a single pill.
Dose: Bictegravir 50 mg/Emtricitabine 200 mg /Tenofovir alafenamide 25 mg Route of adminstration: oral Schedule of administration: once a day for 96 weeks.

Locations

Country	Name	City	State
Spain	Hospital Fundación Alcorcón	Alcorcón	Madrid
Spain	H. de Elche	Alicante
Spain	H. de Torrecárdenas	Almería
Spain	H. Clinic	Barcelona
Spain	H. de Bellvitge	Barcelona
Spain	H. de Igualada	Barcelona
Spain	H. del Mar	Barcelona
Spain	H. San Joan de Deu	Barcelona
Spain	H. Sant Creu y Sant Pau	Barcelona
Spain	H. Vall de Hebron	Barcelona
Spain	CHUAC	Coruña
Spain	H. Universitario de Guadalajara	Guadalajara
Spain	H. Juan Ramón Jimenez	Huelva
Spain	H. Infanta Leonor	Madrid
Spain	H. La Princesa	Madrid
Spain	H. Príncipe de asturias	Madrid
Spain	H. Univ. La Paz	Madrid
Spain	H. Univ. Puerta de Hierro	Madrid
Spain	H. Costa del Sol	Marbella
Spain	H. Reina Sofía	Murcia
Spain	H. Central de Asturias	Oviedo
Spain	H. Son Espases	Palma De Mallorca
Spain	H. Son Llatzer	Palma De Mallorca
Spain	H. de Valme	Sevilla
Spain	H. Joan XXIII	Tarragona
Spain	H. Clínico Univ. de Valencia	Valencia
Spain	H Clinico Univ. de Valladolid	Valladolid
Spain	H. Alvaro Cunquerio	Vigo
Spain	H. Clinico Univ. Lozano Bleza	Zaragoza

Sponsors (2)

Lead Sponsor	Collaborator
Fundacion SEIMC-GESIDA	ViiV Healthcare

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with plasma HIV-1 RNA =50 copies/mL		Week 48
Secondary	Proportion of patients with plasma HIV-1 RNA =50 copies/mL		week 96
Secondary	Proportion of patients with plasma HIV-1 RNA <50 copies/mL		Week 48 and week 96
Secondary	Absolute weight		Basal, week 48 y week 96
Secondary	BMI change		Basal, week 48 y week 96
Secondary	Proportion of patients with weight change >5%		Basal, week 48 y week 96
Secondary	Absolute values in CD4+ cells count		Basal, week 48 y week 96
Secondary	Changes in CD4+ cells count		Basal, week 48 y week 96
Secondary	Absolute values CD4:CD8 ratio		Basal, week 48 y week 96
Secondary	Changes CD4:CD8 ratio		Basal, week 48 y week 96
Secondary	Change in total and regional (trunk and extremities) fat by DXA		Basal, week 48 y week 96
Secondary	Change in total and regional (trunk and extremities) fat-free mass by DXA		Basal, week 48 y week 96
Secondary	Change in lumbar and hip bone mineral density (BMD) by DXA		Basal, week 48 y week 96
Secondary	Change trabecular bone score (TBS) by DXA		Basal, week 48 y week 96
Secondary	Change in subcutaneous and visceral fat (CT)		Basal, week 48 y week 96
Secondary	Change in fasting glucose cholesterol, triglycerides), and FIB-4 score		Basal, week 48 y week 96
Secondary	Change insulin cholesterol, triglycerides), and FIB-4 score		Basal, week 48 y week 96
Secondary	Change in HOMA-IR cholesterol, triglycerides), and FIB-4 score		Basal, week 48 y week 96
Secondary	Change in HbA1c cholesterol, triglycerides), and FIB-4 score		Basal, week 48 y week 96
Secondary	Change in plasma lipids (total, HDL, and LDL) cholesterol, triglycerides), and FIB-4 score		Basal, week 48 y week 96
Secondary	Changes in estimated glomerular filtration rate (CKD-EPI)		Basal, week 48 y week 96
Secondary	Changes in urinary protein/creatinine		Basal, week 48 y week 96
Secondary	Change in blood pressure	Systolic and Diastolic Blood Pressure	Basal, week 48 y week 96
Secondary	Change in sleep quality (Pittsburg Sleep Quality Index)	Pittsburg Sleep Quality Index	From basal, until week 96 , in each visit
Secondary	Change in anxiety and depression (HAD) quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM	Anxiety and depression (HAD) questionnaire	From basal, until week 96 , in each visit
Secondary	Change in quality of life (HIV Symptom Index questionnaire / Symptom Distress Module (HIV-SI/SDM)	Quality of life (HIV-SI/SDM) questionnaire	From basal, until week 96 , in each visit
Secondary	Incidence and severity of adverse events (clinical and laboratory)		From basal, until week 96 , in each visit
Secondary	Incidence of adverse events leading to treatment discontinuation.		From basal, until week 96 , in each visit
Secondary	Incidence of genotypic resistance mutations in participants with virological failure		Week 48 and week 96