Dose Ranging Study of GSK1265744 Plus Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus-1 (HIV-1) Virologic Suppression Followed by Virologic Suppression Maintenance by GSK1265744 Plus Rilpivirine

NCT ID: NCT01641809

Last Updated: 2020-01-30

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-08-06

Study Completion Date

2019-01-15

Brief Summary

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The study is designed to select a dose of GSK1265744 primarily on the basis of antiviral activity and tolerability in HIV-1 infected, antiretroviral naive subjects.

This study consists of two parts:

Induction Phase: Approximately 200 subjects will be randomized (50 subjects in each of the 4 treatment arms). The Induction Phase consists of a 24 week dose-ranging evaluation of GSK1265744 at blinded doses of 10 mg, 30 mg and 60 mg once-daily and a control arm of open-label efavirenz (EFV) 600 mg once daily. The background dual nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy (ART) for all arms will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) as selected by the Investigator. Subjects randomized to a GSK1265744 containing arm, who successfully complete 24 weeks on study and demonstrate virologic suppression (defined as having a plasma HIV-1 ribonucleic acid \[RNA\] \<50 copies per milliliter \[c/mL\] before Week 24, with no signs of virologic rebound) will become eligible for the Maintenance Phase of this study.

Maintenance Phase: The background NRTIs will be discontinued and the subjects will continue their randomized dose of GSK1265744 in combination with rilpivirine (RPV) 25 mg once-daily for an additional 72 weeks. The Maintenance phase will evaluate the ability of this two drug ART regimen to maintain virologic suppression through Week 48, Week 72 and Week 96. Subjects randomized to the EFV arm will continue on their randomized regimen through Week 96.

After completion of the maintenance phase, subjects could enroll in the Open-Label Phase to continue GSK1265744 + RPV treatment as long as they continue to derive clinical benefit and until it is locally approved and commercially available.

Detailed Description

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Conditions

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Infection, Human Immunodeficiency Virus HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Arm 1 GSK1265744 10 mg

In the Induction Phase subjects will receive oral tablets of GSK1265744 10 mg + matching placebo + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 10 mg + matching placebo + Rilpivirine 25 mg once daily from Week 24 to Week 96.

Group Type EXPERIMENTAL

GSK1265744 10 mg

Intervention Type DRUG

GSK1265744 10 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Rilpivirine 25 mg

Intervention Type DRUG

Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Placebo

Intervention Type DRUG

Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.

Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Intervention Type DRUG

The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Arm 2 GSK1265744 30 mg

In the Induction Phase subjects will receive oral tablets of GSK1265744 30 mg + matching placebo + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 30 mg + matching placebo + Rilpivirine 25 mg once daily from Week 24 to Week 96.

Group Type EXPERIMENTAL

GSK1265744 30 mg

Intervention Type DRUG

GSK1265744 30 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Rilpivirine 25 mg

Intervention Type DRUG

Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Placebo

Intervention Type DRUG

Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.

Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Intervention Type DRUG

The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Arm 3 GSK1265744 60 mg

In the Induction Phase subjects will receive oral tablets of GSK1265744 60 mg + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 60 mg + Rilpivirine 25 mg once daily from Week 24 to Week 96.

Group Type EXPERIMENTAL

GSK1265744 60 mg

Intervention Type DRUG

GSK1265744 60 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Rilpivirine 25 mg

Intervention Type DRUG

Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Intervention Type DRUG

The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Arm 4 Efavirenz 600 mg

In the Induction Phase and Maintenance Phase subjects will receive oral tablets of Efavirenz 600 mg + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine).

Group Type ACTIVE_COMPARATOR

Efavirenz 600 mg

Intervention Type DRUG

Efavirenz 600 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase and Maintenance Phase of the study.

Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Intervention Type DRUG

The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Interventions

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GSK1265744 10 mg

GSK1265744 10 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Intervention Type DRUG

GSK1265744 30 mg

GSK1265744 30 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Intervention Type DRUG

GSK1265744 60 mg

GSK1265744 60 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

Intervention Type DRUG

Efavirenz 600 mg

Efavirenz 600 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase and Maintenance Phase of the study.

Intervention Type DRUG

Rilpivirine 25 mg

Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

Intervention Type DRUG

Placebo

Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.

Intervention Type DRUG

Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infected male or female subjects \>= 18 years of age
* Screening plasma HIV-1 RNA \>=1000 c/mL
* CD4+ cell count \>=200 cells/millimeter (mm)\^3
* ART-naive defined as having =\<10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection
* Female subjects of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy during the study

Exclusion Criteria

* Any evidence at screening of an active Centers for Disease and Prevention Control (CDC) Category C disease
* Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
* History of ongoing or clinically relevant hepatitis within the previous 6 months, and subjects with moderate to severe hepatic impairment will be excluded
* Women who are breastfeeding
* Subject, who in the investigator's judgment, poses a significant suicide risk
* Any clinically significant finding on screening or baseline electrocardiograph (ECG)
* The presence of any specific laboratory abnormalities at Screening
* History of cardiac disease
* Clinically relevant pancreatitis
* Subjects who are unlikely to complete the dosing schedule due to a pre-existing physical or mental condition
* Any condition which impairs the absorption, distribution, metabolism or excretion of the investigational product
* Any evidence of primary resistance based upon the presence of a major resistance associated mutation in the Screening HIV genotype, or any historical genotype
* Treatment with any protocol-specified excluded medication
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

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GSK Investigational Site

Birmingham, Alabama, United States

Site Status

GSK Investigational Site

Phoenix, Arizona, United States

Site Status

GSK Investigational Site

Little Rock, Arkansas, United States

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GSK Investigational Site

Bakersfield, California, United States

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GSK Investigational Site

Beverly Hills, California, United States

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GSK Investigational Site

Long Beach, California, United States

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GSK Investigational Site

Los Angeles, California, United States

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GSK Investigational Site

San Francisco, California, United States

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GSK Investigational Site

Denver, Colorado, United States

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GSK Investigational Site

Washington D.C., District of Columbia, United States

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GSK Investigational Site

Washington D.C., District of Columbia, United States

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GSK Investigational Site

Fort Lauderdale, Florida, United States

Site Status

GSK Investigational Site

Fort Lauderdale, Florida, United States

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GSK Investigational Site

Ft. Pierce, Florida, United States

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GSK Investigational Site

Miami, Florida, United States

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GSK Investigational Site

Oakland Park, Florida, United States

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GSK Investigational Site

Orlando, Florida, United States

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GSK Investigational Site

West Palm Beach, Florida, United States

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GSK Investigational Site

Atlanta, Georgia, United States

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GSK Investigational Site

Augusta, Georgia, United States

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GSK Investigational Site

Macon, Georgia, United States

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GSK Investigational Site

Savannah, Georgia, United States

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GSK Investigational Site

Indianapolis, Indiana, United States

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GSK Investigational Site

Boston, Massachusetts, United States

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GSK Investigational Site

Minneapolis, Minnesota, United States

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GSK Investigational Site

Kansas City, Missouri, United States

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GSK Investigational Site

Omaha, Nebraska, United States

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GSK Investigational Site

Las Vegas, Nevada, United States

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GSK Investigational Site

Hillsborough, New Jersey, United States

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GSK Investigational Site

Neptune City, New Jersey, United States

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GSK Investigational Site

Albany, New York, United States

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GSK Investigational Site

Buffalo, New York, United States

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GSK Investigational Site

New York, New York, United States

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GSK Investigational Site

Valhalla, New York, United States

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GSK Investigational Site

Chapel Hill, North Carolina, United States

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GSK Investigational Site

Providence, Rhode Island, United States

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GSK Investigational Site

Charleston, South Carolina, United States

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GSK Investigational Site

Austin, Texas, United States

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GSK Investigational Site

Dallas, Texas, United States

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GSK Investigational Site

Annandale, Virginia, United States

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GSK Investigational Site

Vancouver, British Columbia, Canada

Site Status

GSK Investigational Site

Vancouver, British Columbia, Canada

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GSK Investigational Site

Toronto, Ontario, Canada

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GSK Investigational Site

Toronto, Ontario, Canada

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GSK Investigational Site

Toronto, Ontario, Canada

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GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

GSK Investigational Site

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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Mills A, Richmond GJ, Newman C, Osiyemi O, Cade J, Brinson C, De Vente J, Margolis DA, Sutton KC, Wilches V, Hatch S, Roberts J, McCoig C, Garris C, Vandermeulen K, Spreen WR. Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. AIDS. 2022 Feb 1;36(2):195-203. doi: 10.1097/QAD.0000000000003085.

Reference Type DERIVED
PMID: 34652287 (View on PubMed)

Patel P, Xue Z, King KS, Parham L, Ford S, Lou Y, Bakshi KK, Sutton K, Margolis D, Hughes AR, Spreen WR. Evaluation of the effect of UGT1A1 polymorphisms on the pharmacokinetics of oral and long-acting injectable cabotegravir. J Antimicrob Chemother. 2020 Aug 1;75(8):2240-2248. doi: 10.1093/jac/dkaa147.

Reference Type DERIVED
PMID: 32361755 (View on PubMed)

Margolis DA, Brinson CC, Smith GHR, de Vente J, Hagins DP, Eron JJ, Griffith SK, Clair MHS, Stevens MC, Williams PE, Ford SL, Stancil BS, Bomar MM, Hudson KJ, Smith KY, Spreen WR; LAI116482 Study Team. Cabotegravir plus rilpivirine, once a day, after induction with cabotegravir plus nucleoside reverse transcriptase inhibitors in antiretroviral-naive adults with HIV-1 infection (LATTE): a randomised, phase 2b, dose-ranging trial. Lancet Infect Dis. 2015 Oct;15(10):1145-1155. doi: 10.1016/S1473-3099(15)00152-8. Epub 2015 Jul 19.

Reference Type DERIVED
PMID: 26201299 (View on PubMed)

Other Identifiers

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116482

Identifier Type: -

Identifier Source: org_study_id

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