Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure

HIV Infection Clinical Trial

— ASPIRE  

Official title:

Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02263326
• Other study ID #: ASPIRE
• Status: Completed
• Phase: Phase 3
• Start date: December 2014
• Est. completion date: September 2017

Study information

• Verified date: October 2019
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: September 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• dolutegravir
50 mg tablet by mouth once daily for 48 weeks
• lamivudine
300 mg tablet by mouth once daily for 48 weeks
• Continue current antiretroviral regimen
Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Cornell University	New York	New York
United States	University of California San Diego	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Babafemi Taiwo	ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Residual Viremia by HIV-1 Single-copy Assay	Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis	48 weeks
Primary	Proportion of Participants With Treatment Failure	Proportion of participants with treatment failure (defined as virologic failure (HIV RNA >50 copies/mL), loss to follow-up, or treatment discontinuation) between those who switch to DTG + lamivudine and those who continue their current ART regimen	24 weeks
Secondary	Proportion of Participants With Virologic Success	Proportion of participants with virologic success (<50 copies/mL) based on FDA snapshot definition	48 weeks
Secondary	Change in CD4 Count From Baseline to Week 48	Change in CD4 count between arms will be presented in the attached statistical analysis table	Baseline and 48 weeks
Secondary	Change in Total Cholesterol From Baseline to Week 48	Change in Total Cholesterol between arms will be presented in the attached statistical analysis table	Baseline and 48 weeks
Secondary	Change in LDL Cholesterol From Baseline to Week 48	Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table	Baseline and Week 48
Secondary	Change in Creatinine Clearance From Baseline to Week 48	Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table	Baseline and Week 48
Secondary	Drug Resistance Associated Mutations	Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure	48 weeks