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

Primary Purpose

HIV Infection

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
dolutegravir
lamivudine
Continue current antiretroviral regimen
Sponsored by
Babafemi Taiwo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of California San Diego
  • Emory University
  • Northwestern University
  • Brigham and Women's Hospital
  • Cornell University
  • University of Cincinnati
  • The Ohio State University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

dolutegravir plus lamivudine

Continue current ART regimen

Arm Description

dolutegravir 50 mg plus lamivudine 300 mg once daily

Continue current DHHS recommended or alternative three-drug antiretroviral regimen

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Proportion of Participants With Virologic Success
Proportion of participants with virologic success (<50 copies/mL) based on FDA snapshot definition
Change in CD4 Count From Baseline to Week 48
Change in CD4 count between arms will be presented in the attached statistical analysis table
Change in Total Cholesterol From Baseline to Week 48
Change in Total Cholesterol between arms will be presented in the attached statistical analysis table
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
Change in Creatinine Clearance From Baseline to Week 48
Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table
Drug Resistance Associated Mutations
Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure

Full Information

First Posted
October 6, 2014
Last Updated
October 10, 2019
Sponsor
Babafemi Taiwo
Collaborators
ViiV Healthcare
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1. Study Identification

Unique Protocol Identification Number
NCT02263326
Brief Title
Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure
Acronym
ASPIRE
Official Title
Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure (ASPIRE) Study
Study Type
Interventional

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
July 2017 (Actual)
Study Completion Date
September 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Babafemi Taiwo
Collaborators
ViiV Healthcare

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
89 (Actual)

8. Arms, Groups, and Interventions

Arm Title
dolutegravir plus lamivudine
Arm Type
Experimental
Arm Description
dolutegravir 50 mg plus lamivudine 300 mg once daily
Arm Title
Continue current ART regimen
Arm Type
Active Comparator
Arm Description
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Intervention Type
Drug
Intervention Name(s)
dolutegravir
Other Intervention Name(s)
TIVICAY, DTG
Intervention Description
50 mg tablet by mouth once daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
lamivudine
Other Intervention Name(s)
EPIVIR, 3TC
Intervention Description
300 mg tablet by mouth once daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
Continue current antiretroviral regimen
Intervention Description
Continue current DHHS recommended or alternative three-drug antiretroviral regimen
Primary Outcome Measure Information:
Title
Proportion of Participants With Treatment Failure
Description
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
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Proportion of Participants With Virologic Success
Description
Proportion of participants with virologic success (<50 copies/mL) based on FDA snapshot definition
Time Frame
48 weeks
Title
Change in CD4 Count From Baseline to Week 48
Description
Change in CD4 count between arms will be presented in the attached statistical analysis table
Time Frame
Baseline and 48 weeks
Title
Change in Total Cholesterol From Baseline to Week 48
Description
Change in Total Cholesterol between arms will be presented in the attached statistical analysis table
Time Frame
Baseline and 48 weeks
Title
Change in LDL Cholesterol From Baseline to Week 48
Description
Change in Low-density lipoprotein (LDL) cholesterol between arms will be presented in the attached statistical analysis table
Time Frame
Baseline and Week 48
Title
Change in Creatinine Clearance From Baseline to Week 48
Description
Change in Creatinine Clearance between arms will be presented in the attached statistical analysis table
Time Frame
Baseline and Week 48
Title
Drug Resistance Associated Mutations
Description
Drug resistance mutations measured by HIV genotyping in patients with confirmed virologic failure
Time Frame
48 weeks
Other Pre-specified Outcome Measures:
Title
Residual Viremia by HIV-1 Single-copy Assay
Description
Difference in HIV-1 detection by the HIV-1 single copy assay between arms will be presented in statistical analysis
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Babafemi Taiwo, MBBS
Organizational Affiliation
Northwestern University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Cornell University
City
New York
State/Province
New York
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29293895
Citation
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.
Results Reference
derived

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Dolutegravir Antiretroviral Strategy to Promote Improvement and Reduce Drug Exposure

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