Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure

NCT ID: NCT02263326

Last Updated: 2019-10-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2017-09-30

Brief Summary

HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24

Detailed Description

DESIGN HIV-1 infected subjects with CD4 nadir > 200 cells/mm3, no history of virologic failure and plasma HIV RNA <50 copies/mL for at least 48 weeks while on any United States Department of Health and Human Services (DHHS) recommended or alternative three-drug antiretroviral regimen will be randomized to dolutegravir (DTG) plus lamivudine (Arm 1) or continuation of their current regimen (Arm 2) for 48 weeks. The primary endpoint is virologic failure defined as confirmed plasma HIV-1 RNA > 50 copies/mL before or at Week 24

All subjects will undergo routine monitoring including plasma HIV-1 RNA, CD4/CD8 count, hematology, chemistry and fasting lipids. Resistance testing will be done in all patients who experience virologic failure. Single-copy HIV-1 assay will be done to quantify residual viremia.

DURATION 48 weeks

SAMPLE SIZE 90 subjects

POPULATION HIV-1-infected men and women, 18 years and older, with CD4 nadir > 200 cells/mm3, no baseline resistance, no history of virologic failure, and HIV RNA <50 copies/mL for at least 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug regimen

REGIMEN Subjects will be randomized (1:1) to:

Arm 1: dolutegravir 50 mg plus lamivudine 300 mg once daily OR Arm 2: Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Conditions

HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dolutegravir plus lamivudine

dolutegravir 50 mg plus lamivudine 300 mg once daily

Group Type: EXPERIMENTAL

dolutegravir

Intervention Type: DRUG

50 mg tablet by mouth once daily for 48 weeks

lamivudine

Intervention Type: DRUG

300 mg tablet by mouth once daily for 48 weeks

Continue current ART regimen

Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Group Type: ACTIVE_COMPARATOR

Continue current antiretroviral regimen

Intervention Type: DRUG

Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Interventions

dolutegravir

50 mg tablet by mouth once daily for 48 weeks

Intervention Type: DRUG

lamivudine

300 mg tablet by mouth once daily for 48 weeks

Intervention Type: DRUG

Continue current antiretroviral regimen

Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Intervention Type: DRUG

Other Intervention Names

TIVICAY, DTG; EPIVIR, 3TC

Eligibility Criteria

Inclusion Criteria

• HIV-1 Infection
• HIV-1 RNA <50 copies/mL on all measurements within 48 weeks prior to study entry while on any DHHS recommended or alternative three-drug antiretroviral regimen. (A history of switching for simplification and/or tolerability is allowed. At least two measurements within the previous 48 weeks are required prior to study screening.)
• No history of virologic failure, defined as consecutive HIV RNA > 50 copies/mL after 12 months of initiating ART. An isolated (non-consecutive) HIV RNA > 50 copies/mL (but less than 400 copies/mL) is permitted after 12 months of initiating ART but not in the 48-week window prior to study entry.
• Screening plasma HIV RNA < 20 copies/mL using the COBAS AmpliPrep/COBAS TaqMan HIV-1 Test V2.0, obtained within 45 days prior to study entry
• Nadir CD4 count >200 cells/mm
• Pretreatment genotype documenting no mutations in the protease or reverse transcriptase genes
• No known resistance to integrase inhibitors
• Laboratory values obtained within 45 days prior to study entry:

ANC >750 Hemoglobin >10 g/dL Platelets >50,000 Calculated creatinine clearance (CrCl) >50 mL/min

• Negative serum or urine pregnancy test
• Men and women age greater or equal to 18 years.
• Ability to continue current regimen (i.e, have uninterrupted access)
• No evidence of chronic hepatitis B

Exclusion Criteria

• Serious illness or AIDS-related complication within 21 days of screening requiring systemic treatment and/or hospitalization
• Treatment within 30 days prior to study entry with immune modulators
• Vaccination within 7 days
• Active HCV treatment or anticipated need for treatment within study period. (HCV infection alone is not exclusionary)
• Unstable liver disease or severe hepatic impairment
• Known allergy or hypersensitivity to DTG or lamivudine.
• Active drug or alcohol use or dependence that could interfere with adherence to study requirements
• ALT (alanine aminotransferase) >5 x ULN (upper limit of normal) OR ALT >3 x ULN and total bilirubin >1.5 x ULN (with 35% direct bilirubin)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: collaborator

Babafemi Taiwo

OTHER

Sponsor Role: lead

Responsible Party

Babafemi Taiwo

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Babafemi Taiwo, MBBS

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

University of California San Diego

San Diego, California, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Cornell University

New York, New York, United States

University of Cincinnati

Cincinnati, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Countries

United States

References

Taiwo BO, Marconi VC, Berzins B, Moser CB, Nyaku AN, Fichtenbaum CJ, Benson CA, Wilkin T, Koletar SL, Colasanti J, Acosta EP, Li JZ, Sax PE. Dolutegravir Plus Lamivudine Maintains Human Immunodeficiency Virus-1 Suppression Through Week 48 in a Pilot Randomized Trial. Clin Infect Dis. 2018 May 17;66(11):1794-1797. doi: 10.1093/cid/cix1131.

Reference Type: DERIVED

PMID: 29293895 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

ASPIRE

Identifier Type: -

Identifier Source: org_study_id