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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03539224
Recruitment Status : Active, not recruiting
First Posted : May 29, 2018
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
Instituto de Investigación Hospital Universitario La Paz

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

Condition or disease Intervention/treatment Phase
HIV-1-infection Drug: Dolutegravir (DTG) Drug: Lamivudine (3TC) Phase 2

Detailed Description:
Proof of concept trial evaluating safety and efficacy of treatment with Dolutegravir (DTG) + lamivudine (3TC) once daily in suppressed participants with history of previous treatment with 3TC or emtricitabine (FTC). Half of the participants will have history of failure with 3TC or FTC and M184V/I or K65R/E/N mutations in previous plasma genotypes, although to be eligible these mutations cannot be detectable at study entry in proviral DNA.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single arm opened with Intervention Type of Drug: Dolutegravir (DTG) and Lamivudina (3TC)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.
Actual Study Start Date : November 2, 2017
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : July 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dolutegravir (DTG) + Lamivudine (3TC)
Eligible subjects will receive one 50 mg tablet of DTG plus 300 mg 3TC tablet orally once daily upto 48 weeks
Drug: Dolutegravir (DTG)
DTG 50 mg tablet will be orally administered once daily with or without food upto 48 weeks
Other Name: Tivicay

Drug: Lamivudine (3TC)
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.
Other Name: Epivir




Primary Outcome Measures :
  1. Proportion of patients with undetectable viral load (<50 copies / mL) at 48 weeks [ Time Frame: Week 48 ]
    - 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.


Secondary Outcome Measures :
  1. Proportion of patients with virological failure at 24 weeks [ Time Frame: Week 24 ]
    Proportion of patients with viral load <50 copies/ml at week 24, according to the FDA snapshot algorithm in the population "by intention to treat-exposed".

  2. Proportion of patients with virological failure at 48 weeks [ Time Frame: Week 48 ]
    Proportion of patients with virological failure at week 48 according to the FDA snapshot algorithm.

  3. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Since baseline visits to week 48 ]
    Incidence of adverse events and discontinuation of treatment due to toxicity or intolerance.

  4. Evaluation of the appearance of genotypic resistance mutations (1) [ Time Frame: Week 48 ]
    Incidence of genotypic resistance mutations in patients with virological failure at week 48. Description and frequency of genotypic resistance mutations.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infected patients.
  2. Age> 18 years.
  3. Receiving stable antiretroviral treatment for at least 3 months.
  4. Current or historical treatment with 3TC or FTC.
  5. Willing to change antiretroviral treatment due to intolerance or interest in simplification.
  6. Undetectable viral load (<50 cop/mL) for at least 1 year prior to the inclusion. A single viral load >50cop/ml (≤500 copies/ml) is allowed before the three months prior to inclusion in the study, preceded and followed by an undetectable determination.
  7. Current level of CD4> 350 cells/μL.
  8. Naïve to integrase inhibitors.
  9. Patient able to understand and give written informed consent.
  10. 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.
  11. 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.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03539224


Locations
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Spain
Hospital 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario La Paz
Madrid, Spain, 28046
Sponsors and Collaborators
Instituto de Investigación Hospital Universitario La Paz

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Responsible Party: Instituto de Investigación Hospital Universitario La Paz
ClinicalTrials.gov Identifier: NCT03539224    
Other Study ID Numbers: ART-PRO
2017-000151-10 ( EudraCT Number )
First Posted: May 29, 2018    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lamivudine
Dolutegravir
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
HIV Integrase Inhibitors
Integrase Inhibitors