Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.

NCT03539224 | Unknown Phase 2 DMC

• 2 other identifiers: ART-PRO2017-000151-10
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

Phase IIa, open clinical trial, pilot, single arm and proof of concept.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks

  \- Efficacy: Proportion of patients with undetectable viral load (\<50 copies / mL) at 48 weeks of follow-up, according to the FDA snapshot algorithm in the population "by intention to treat-exposed". The intention-to-treat population includes all patients who have received at least one dose of DTG and 3TC.

  Week 48

Secondary Outcomes (4)

• Proportion of patients with virological failure at 24 weeks

  Week 24

• Proportion of patients with virological failure at 48 weeks

  Week 48

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Since baseline visits to week 48

• Evaluation of the appearance of genotypic resistance mutations (1)

  Week 48

Study Arms (1)

Dolutegravir (DTG) + Lamivudine (3TC)

EXPERIMENTAL

Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks

Drug: Dolutegravir (DTG); Drug: Lamivudine (3TC)

Interventions

Dolutegravir (DTG) DRUG

DTG 50 mg tablet will be orally administered once daily with or without food upto 48 weeks

Also known as: Tivicay

Dolutegravir (DTG) + Lamivudine (3TC)

Lamivudine (3TC) DRUG

Lamivudine will be dispensed as 300 mg white, diamond shaped, scored, film coated tablets. It will be orally administered once daily with or without food upto 48 weeks.

Also known as: Epivir

Dolutegravir (DTG) + Lamivudine (3TC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infected patients.
• Age\> 18 years.
• Receiving stable antiretroviral treatment for at least 3 months.
• Current or historical treatment with 3TC or FTC.
• Willing to change antiretroviral treatment due to intolerance or interest in simplification.
• Current level of CD4\> 350 cells/μL.
• Naïve to integrase inhibitors.
• Patient able to understand and give written informed consent.
• For those included in group 1 (20 patients): No previous history of virological failure with ART regimen that included 3TC or FTC or previous virological failure had a population genotype without M184V/I or K65R/E/N mutations.
• For those included in group 2 (20 patients): previous history of virological failure with ART regimen that included 3TC or FTC and historical genotype with M184V/I or K65R/E/N mutations.

You may not qualify if:

• Detection of any of the following mutations in proviral DNA in peripheral blood by conventional sequencing: M184V/I or K65R/E/N.
• Pregnant, lactating or child-bearing women who do not commit to using an adequate contraceptive method.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead

Study Sites (2)

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (2)

• De Miguel Buckley R, Rial-Crestelo D, Montejano R, Pinto A, Jimenez-Gonzalez M, Lagarde M, Esteban-Cantos A, Aranguren-Rivas P, Cadinanos J, Bisbal O, Castro JM, Santacreu-Guerrero M, Bermejo-Plaza L, Moreno V, Hernando A, Martin-Carbonero L, Rubio R, Delgado R, Arribas JR, Pulido F; Antiretroviral Treatment Guided by Proviral Genotype (ART-PRO) Study Group. Long-term Evaluation of Residual Viremia in a Clinical Trial of Dolutegravir Plus Lamivudine as Maintenance Treatment for Participants With and Without Prior Lamivudine Resistance. Open Forum Infect Dis. 2022 Nov 8;9(11):ofac610. doi: 10.1093/ofid/ofac610. eCollection 2022 Nov.

  PMID: 36447613 DERIVED

• De Miguel R, Rial-Crestelo D, Dominguez-Dominguez L, Montejano R, Esteban-Cantos A, Aranguren-Rivas P, Stella-Ascariz N, Bisbal O, Bermejo-Plaza L, Garcia-Alvarez M, Alejos B, Hernando A, Santacreu-Guerrero M, Cadinanos J, Mayoral M, Castro JM, Moreno V, Martin-Carbonero L, Delgado R, Rubio R, Pulido F, Arribas JR; ART-PRO, PI16/00837-PI16/00678 study group. Dolutegravir plus lamivudine for maintenance of HIV viral suppression in adults with and without historical resistance to lamivudine: 48-week results of a non-randomized, pilot clinical trial (ART-PRO). EBioMedicine. 2020 May;55:102779. doi: 10.1016/j.ebiom.2020.102779. Epub 2020 May 11.

  PMID: 32408111 DERIVED

MeSH Terms

Interventions

dolutegravir; Lamivudine

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm opened with Intervention Type of Drug: Dolutegravir (DTG) and Lamivudina (3TC)

Study Record Dates

• First Submitted: April 2, 2018
• First Posted: May 29, 2018
• Study Start: November 2, 2017
• Primary Completion: May 31, 2021
• Study Completion: July 31, 2021
• Last Updated: July 7, 2020

Record last verified: 2020-07

Locations

ES (2)