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Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir (VIKING-4)

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Dolutegravir 50 mg twice daily

Dolutegravir placebo twice daily

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring ART-experienced, GSK1349572, Integrase inhibitor resistance, Dolutegravir

Eligibility Criteria

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

Inclusion Criteria:

Screening plasma HIV-1 RNA ≥1000 copies/mL
ART-experienced, INI-experienced, DTG naïve
Current virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen
The subject's HIV-1 shows genotypic resistance to RAL or ELV at Screening
Subject has been on stable ART for at least one month prior to Screening and through Day 1(with exceptions for ETV, EFV and NVP that can be interrupted within 14 days of Day 1, see Exclusion Criterion)
Documented resistance to at least one drug from each of two or more of any approved classes of ART other than integrase inhibitors
Be able to receive at least one fully active drug as part of the OBR from Day 8
Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
Willing and able to understand and provide signed and dated written informed consent prior to Screening.

Exclusion Criteria:

Women who are pregnant or breast feeding
An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ <200c/mm3)
Moderate to severe hepatic impairment as defined by Child-Pugh classification
Anticipated need for HCV therapy during the first 24 weeks of the study
Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding
Allergy or intolerance to the study drugs or their components or drugs of their class
Malignancy within the past 6 months
Treatment with an HIV-1 therapeutic vaccine within 90 days of Screening
Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening
Treatment with any agent, other than licensed ART, with documented in vitro/vivo activity against HIV-1 within 28 days of first dose of investigational product (with the exception of entecavir if required for Hep B treatment)
Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine may be used if coadministered with lopinavir/ritonavir or darunavir/ritonavir)
Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within 28 days prior to Screening
Exposure to an experimental drug or vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, which ever is longer, prior to the first dose of IP.
Any acute or verified Grade 4 laboratory abnormality (with the exception of Grade 4 lipids) at Screening
ALT> 5 times the upper limit of normal (ULN) at Screening
ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

DTG 50 mg BID

Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase

Arm Description

Subjects will receive dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all subjects will continue to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.

Subjects will receive matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all subjects will continue to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.

Outcomes

Primary Outcome Measures

Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1) and Day 8. Change from Baseline was calculated as the value at Day 8 minus the value at Baseline (Day 1). The analysis was performed using statistical modeling correcting for Baseline plasma HIV-1 RNA, Baseline Dolutegravir (DTG) fold change (FC), the overall susceptibility score (OSS) of the failing regimen, and the interaction between DTG FC and treatment. Means and differences were calculated using the average Baseline DTG FC of the entire Intent-to-Treat Exposed (ITT-E) Population. The last observation carried forward with discontinuation equals Baseline (LOCFDB) dataset was used for the analysis. For the LOCFDB dataset, missing values were carried forward from the previous, non-missing, available on-treatment assessment, except formissing values due to premature withdrawal or Day 8 missing values, which had the Baseline value imputed.

Secondary Outcome Measures

Absolute Values in Plasma HIV-1 RNA Over Time

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Day 8, Day 28, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, and Week 84. NA indicates data was not available.

Mean Change From Baseline in Plasma HIV-1 RNA Over Time

Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1); Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, and 48. Number of participants with plasma HIV-1 RNA level <50 c/mL was obtained using Food and Drug Administration's (FDA's) snapshot algorithm, where all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) were treated as non-responders. Also, participants who switched their concomitant antiretroviral therapy (ART) prior to the visit of interest as follows were also treated as non-responders: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol; however, the decision to switch is not documented as being before or at the first On-treatment visit after switching to optimized background regimen (OBR) (i.e. Day 28) where HIV-1 RNA is assessed.

Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time

Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1); Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48. Number of participants with plasma HIV-1 RNA level <400 c/mL was obtained using FDA's snapshot algorithm, where all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) were treated as non-responders. Also, participants who switch their concomitant ART prior to the visit of interest as follows were also treated as non-responders: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol; however the decision to switch is not documented as being before or at the first On-treatment visit after switching to OBR (i.e. Day 28) where HIV-1 RNA is assessed.

Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84.

Median Change From Baseline in CD4+ Cell Counts Over Time

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 28; and Weeks 12, 24, and 48.

Median Change From Baseline in CD8+ Cell Counts Over Time

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 28; and Weeks 12, 24, and 48. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT])

The number of participants with HIV-1 disease progression (AIDS or death) was assessed per the Centers for Disease Control and Prevention (CDC) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. The CDC classifies HIV infection as Category A (participants with asymptomatic HIV infection, acute HIV infection with accompanying illness, or persistent generalized lymphadenopathy), Category B (participants with symptomatic non-AIDS condition, i.e., conditions that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or conditions are considered by physicians to have a clinical course or to require management that is complicated by HIV infection), and Category C (includes AIDS indicator conditions as defined by diagnostic or presumptive measures).

Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in other situations. Adverse events were graded for severity according to the Division of AIDS (DAIDS) toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade

Participants with post-Baseline-emergent clinical chemistry toxicities were analyzed. Clinical chemistry toxicities were graded for severity according to the DAIDS toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade

Participants with post-Baseline-emergent hematology toxicities were analyzed. Hematology toxicities were graded for severity according to the DAIDS toxicity scales as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (potentially life threatening).

AUC(0-tau) of DTG

The area under the time concentration curve over the dosing interval (AUC[0-tau]) of DTG was assessed by a population pharmacokinetic (PK) modeling approach using pooled DTG PK data from multiple studies. Blood samples for the determination of plasma DTG concentration were collected at the following time points: pre-dose and 1-3 hours post-dose on Day 8; pre-dose and within a post-dose window (1-3 hours or 4-12 hours) on Day 28 and Week 24. For Day 8 PK, only samples collected from participants randomized to the active DTG arm were analyzed.

Cmax of DTG

The maximal concentration (Cmax) of DTG was assessed by a population PK modeling approach using pooled DTG PK data from multiple studies. Blood samples for the determination of plasma DTG concentration were collected at the following time points: pre-dose and 1-3 hours post-dose on Day 8; pre-dose and within a post-dose window (1-3 hours or 4-12 hours) on Day 28 and Week 24. For Day 8 PK, only samples collected from participants randomized to the active DTG arm were analyzed.

Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24

Blood samples for the determination of plasma DTG pre-dose concentration were collected pre-dose on Day 8, Day 28, and Week 24. For Day 8 PK, only samples collected from participants randomized to the active DTG arm were analyzed. C0 Avg was calculated at Week 24 as the mean of the concentration at Day 8, Day 28, and Week 24.

Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance

For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Day 28, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >1 log10 copies/mL above the nadir value, where nadir is >=400 copies/mL.Treatment-emergent IN mutations are those detected at the time of PDVF but not at Baseline.

Number of Participants With the Indicated Fold Increase in Fold Change (FC) in the 50% Inhibitory Concentration Relative to Wild-type Virus for DTG (i.e. PDVF FC/Baseline FC Ratio) at the Time of PDVF, as a Measure of Phenotypic Resistance

For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Day 28, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >1 log10 copies/mL above the nadir value, where nadir is >=400 copies/mL.

Number of Participants Who Discontinued Study Treatment Due to AEs

The number of participants who permanently discontinued study treatment due to AEs is presented.

Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings

Twelve lead ECG was performed using an automated ECG machine. The number of participants with abnormal-clinically significant ECG findings at any time on-treatment is reported.

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Vital signs including SBP and DBP were measured at Baseline, Week 24 and Week 48. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Change From Baseline in Heart Rate

Vital signs including heart rate was measured at Baseline, Week 24 and Week 48. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Change From Baseline in Albumin Level

Blood samples were collected for the analysis of clinical chemistry parameters such as albumin. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase

Blood samples were collected for the analysis of clinical chemistry parameters such as ALP, ALT, AST and creatine kinase. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels

Blood samples were collected for the analysis of clinical chemistry parameters such as T. Bil and creatinine. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen

Blood samples were collected for the analysis of clinical chemistry parameters such as cholesterol, chloride, CO2/HCO3, glucose, high density lipoprotein (HDL) cholesterol, potassium, LDL cholesterol, sodium, phosphorus inorganic, triglycerides and urea/blood urea nitrogen (BUN). Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Creatinine Clearance

Creatinine clearance was calculated using Cockcroft-Gault formula. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.

Change From Baseline in Lipase Levels

Blood samples were collected for the analysis of clinical chemistry parameters such as lipase level. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet and White Blood Cell (WBC) Count

Blood samples were collected for the analysis of hematology parameters such as basophils, eosinophils. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Hemoglobin Level

Blood samples were collected for the analysis of hematology parameters such as hemoglobin. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Hematocrit Level

Blood samples were collected for the analysis of hematology parameters such as hematocrit level. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Mean Corpuscle Volume

Blood samples were collected for the analysis of hematology parameters such as mean corpuscle volume. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Change From Baseline in Red Blood Cell Count

Blood samples were collected for the analysis of hematology parameters such as RBC. Baseline was defined as the last pre-treatment value. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline. NA indicates data was not available.

Full Information

NCT ID

NCT01568892

First Posted

March 29, 2012

Last Updated

June 14, 2018

Sponsor

ViiV Healthcare

Collaborators

Shionogi, GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT01568892

Brief Title

Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir

Acronym

VIKING-4

Official Title

A Phase III Randomized, Double-blind Study to Demonstrate the Antiviral Activity of Dolutegravir (DTG) 50 mg Twice Daily Versus Placebo Both Co-Administered With a Failing Antiretroviral Regimen Over Seven Days, Followed by an Open Label Phase With All Subjects Receiving DTG 50 mg Twice Daily Co-administered With an Optimised Background Regimen (OBR) in HIV-1 Infected, Integrase Inhibitor Therapy-Experienced and Resistant, Adults

Study Type

Interventional

2. Study Status

Record Verification Date

June 2018

Overall Recruitment Status

Completed

Study Start Date

April 18, 2012 (Actual)

Primary Completion Date

October 31, 2012 (Actual)

Study Completion Date

December 16, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

Collaborators

Shionogi, GlaxoSmithKline

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Study ING116529 is a multicenter, randomized, study with an initial 7 day placebo- controlled, functional monotherapy phase to quantify the antiviral activity attributable to dolutegravir (DTG) in HIV-1 infected, ART-experienced adults who are experiencing virological failure on an Integrase inhibitor containing regimen (current RAL or ELV failures), with evidence of genotypic resistance to RAL or ELV at study entry. Thirty subjects will be randomized (1:1) to receive either DTG 50mg BID (Arm A) or Placebo (Arm B) with the current failing regimen for 7 days (RAL or ELV should be discontinued prior to dosing with DTG). At Day 8, subjects from both arms will enter an open label phase and receive open label DTG 50mg BID with an optimized background regimen containing at least one fully active drug.

Detailed Description

Study ING116529 is a multicenter, randomized, study with an initial 7 day placebo-controlled, functional monotherapy phase to assess the antiviral activity and safety of a dolutegravir (DTG, GSK1349572) containing regimen in HIV-1 infected, ART-experienced adults with virological failure on an integrase inhibitor (INI) containing regimen. Subjects must have evidence of genotypic resistance to raltegravir [RAL] or elvitegravir [ELV] at Screening and documented current or historical genotypic or phenotypic resistance to at least two other antiretroviral therapy drug classes. The study is designed to provide an accurate measure of the intrinsic antiviral activity of DTG 50mg twice daily versus placebo both administered with the current failing regimen in a randomised double-blind phase to Day 8. This will be followed by an open label phase with all subjects receiving DTG 50mg twice daily with an optimized background regimen (containing at least one fully active drug) until subjects no longer derive clinical benefit or until DTG is locally available. Thirty subjects will be randomized (1:1) to receive either DTG 50mg BID (Arm A) or Placebo (Arm B) with the current failing regimen for 7 days (RAL or ELV should be discontinued prior to dosing at Day 1). At Day 8, subjects from both arms will enter an open label phase and receive open label DTG 50mg BID with an optimized background regimen containing at least one fully active drug The primary analysis will be conducted after the last subject enrolled has completed the randomised, double-blind phase at Day 8. Additional analyses may be performed prior to study closure when all ongoing subjects transition to locally available commercial DTG.

6. Conditions and Keywords

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

HIV Infections

Keywords

ART-experienced, GSK1349572, Integrase inhibitor resistance, Dolutegravir

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DTG 50 mg BID

Arm Type

Experimental

Arm Description

Arm Title

Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Dolutegravir 50 mg twice daily

Other Intervention Name(s)

GSK1349572

Intervention Description

Active dolutegravir plus failing background regimen (Day 1 to Day 7). Open label dolutegravir plus optimized background regimen (from Day 8)

Intervention Type

Drug

Intervention Name(s)

Dolutegravir placebo twice daily

Other Intervention Name(s)

GSK1349572 Placebo

Intervention Description

Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)

Primary Outcome Measure Information:

Title

Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8

Description

Time Frame

Baseline and Day 8

Secondary Outcome Measure Information:

Title

Absolute Values in Plasma HIV-1 RNA Over Time

Description

Time Frame

Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Title

Mean Change From Baseline in Plasma HIV-1 RNA Over Time

Description

Time Frame

Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Title

Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time

Description

Time Frame

Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48

Title

Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time

Description

Time Frame

Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48

Title

Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time

Description

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84.

Time Frame

Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Title

Median Change From Baseline in CD4+ Cell Counts Over Time

Description

Time Frame

Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84

Title

Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time

Description

Blood samples were collected for lymphocyte subset assessment by flow cytometry at Baseline; Day 28; and Weeks 12, 24, and 48.

Time Frame

Baseline; Day 28; Weeks 12, 24, and 48

Title

Median Change From Baseline in CD8+ Cell Counts Over Time

Description

Time Frame

Baseline; Day 28; Weeks 12, 24, and 48

Title

Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT])

Description

Time Frame

From the day of the first dose of study drug until early withdrawal or the Week 48 analysis cut-off date (median of 55 study weeks)

Title

Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade

Description

Time Frame

From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Title

Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade

Description

Time Frame

From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Title

Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade

Description

Time Frame

From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Title

AUC(0-tau) of DTG

Description

Time Frame

Day 8, Day 28, and Week 24

Title

Cmax of DTG

Description

Time Frame

Day 8, Day 28, and Week 24

Title

Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24

Description

Time Frame

Day 8, Day 28, and Week 24

Title

Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance

Description

Time Frame

From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Title

Description

For participants meeting one of the criteria for PDVF, plasma samples collected at the time point of virologic failure were tested to evaluate any potential genotypic and/or phenotypic evolution of resistance. The FC in IC50 (50% inhibitory concentration) for DTG relative to wild-type virus was determined for virus isolated at Baseline and at the time of PDVF. The number of participants with the indicated change (ratio) in the two values at the time of PDVF is presented. PDVF was defined as (A) Virologic Non-response: a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Day 28, with subsequent confirmation, unless plasma HIV-1 RNA is <400 copies/mL; confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or (B) Virologic Rebound: confirmed rebound in plasma HIV-1 RNA levels to >=400 copies/mL after prior confirmed suppression to <400 copies/mL; confirmed plasma HIV-1 RNA levels >1 log10 copies/mL above the nadir value, where nadir is >=400 copies/mL.

Time Frame

From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Title

Number of Participants Who Discontinued Study Treatment Due to AEs

Description

The number of participants who permanently discontinued study treatment due to AEs is presented.

Time Frame

From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 study weeks)

Title

Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings

Description

Twelve lead ECG was performed using an automated ECG machine. The number of participants with abnormal-clinically significant ECG findings at any time on-treatment is reported.

Time Frame

Up to Week 24

Title

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Description

Time Frame

Baseline and Weeks 24 and 48

Title

Change From Baseline in Heart Rate

Description

Time Frame

Baseline and Weeks 24 and 48

Title

Change From Baseline in Albumin Level

Description

Time Frame

Baseline, Week 24 and 48

Title

Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Creatinine Clearance

Description

Time Frame

Baseline, Day 8, Day 28, Week 8, Week 16, Week 24, Week 32 and Week 48

Title

Change From Baseline in Lipase Levels

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet and White Blood Cell (WBC) Count

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Hemoglobin Level

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Hematocrit Level

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Mean Corpuscle Volume

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

Title

Change From Baseline in Red Blood Cell Count

Description

Time Frame

Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Screening plasma HIV-1 RNA ≥1000 copies/mL ART-experienced, INI-experienced, DTG naïve Current virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen The subject's HIV-1 shows genotypic resistance to RAL or ELV at Screening Subject has been on stable ART for at least one month prior to Screening and through Day 1(with exceptions for ETV, EFV and NVP that can be interrupted within 14 days of Day 1, see Exclusion Criterion) Documented resistance to at least one drug from each of two or more of any approved classes of ART other than integrase inhibitors Be able to receive at least one fully active drug as part of the OBR from Day 8 Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol) Willing and able to understand and provide signed and dated written informed consent prior to Screening. Exclusion Criteria: Women who are pregnant or breast feeding An active AIDS-defining condition at Screening (except cutaneous Kaposi's sarcoma not requiring systemic therapy or CD4+ <200c/mm3) Moderate to severe hepatic impairment as defined by Child-Pugh classification Anticipated need for HCV therapy during the first 24 weeks of the study Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding Allergy or intolerance to the study drugs or their components or drugs of their class Malignancy within the past 6 months Treatment with an HIV-1 therapeutic vaccine within 90 days of Screening Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening Treatment with any agent, other than licensed ART, with documented in vitro/vivo activity against HIV-1 within 28 days of first dose of investigational product (with the exception of entecavir if required for Hep B treatment) Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine may be used if coadministered with lopinavir/ritonavir or darunavir/ritonavir) Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within 28 days prior to Screening Exposure to an experimental drug or vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, which ever is longer, prior to the first dose of IP. Any acute or verified Grade 4 laboratory abnormality (with the exception of Grade 4 lipids) at Screening ALT> 5 times the upper limit of normal (ULN) at Screening ALT ≥ 3X ULN and bilirubin > 1.5 X ULN (with 35% direct bilirubin) at Screening

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

ViiV Healthcare

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72207

Country

United States

Facility Name

GSK Investigational Site

City

Bakersfield

State/Province

California

ZIP/Postal Code

93301

Country

United States

Facility Name

GSK Investigational Site

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

GSK Investigational Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90069

Country

United States

Facility Name

GSK Investigational Site

City

San Diego

State/Province

California

ZIP/Postal Code

92103-8208

Country

United States

Facility Name

GSK Investigational Site

City

Norwalk

State/Province

Connecticut

ZIP/Postal Code

06850

Country

United States

Facility Name

GSK Investigational Site

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

GSK Investigational Site

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20009

Country

United States

Facility Name

GSK Investigational Site

City

Fort Lauderdale

State/Province

Florida

ZIP/Postal Code

33316

Country

United States

Facility Name

GSK Investigational Site

City

Fort Pierce

State/Province

Florida

ZIP/Postal Code

34982

Country

United States

Facility Name

GSK Investigational Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32803

Country

United States

Facility Name

GSK Investigational Site

City

Augusta

State/Province

Georgia

ZIP/Postal Code

30912

Country

United States

Facility Name

GSK Investigational Site

City

Savannah

State/Province

Georgia

ZIP/Postal Code

31401

Country

United States

Facility Name

GSK Investigational Site

City

Maywood

State/Province

Illinois

ZIP/Postal Code

60153

Country

United States

Facility Name

GSK Investigational Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

GSK Investigational Site

City

Hillsborough

State/Province

New Jersey

ZIP/Postal Code

08844

Country

United States

Facility Name

GSK Investigational Site

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Facility Name

GSK Investigational Site

City

Buffalo

State/Province

New York

ZIP/Postal Code

14215

Country

United States

Facility Name

GSK Investigational Site

City

New York

State/Province

New York

ZIP/Postal Code

10011

Country

United States

Facility Name

GSK Investigational Site

City

Valhalla

State/Province

New York

ZIP/Postal Code

10595

Country

United States

Facility Name

GSK Investigational Site

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

Facility Name

GSK Investigational Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19140

Country

United States

Facility Name

GSK Investigational Site

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

GSK Investigational Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

GSK Investigational Site

City

Annandale

State/Province

Virginia

ZIP/Postal Code

22003

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25321146

Citation

Akil B, Blick G, Hagins DP, Ramgopal MN, Richmond GJ, Samuel RM, Givens N, Vavro C, Song IH, Wynne B, Ait-Khaled M; VIKING-4 study team. Dolutegravir versus placebo in subjects harbouring HIV-1 with integrase inhibitor resistance associated substitutions: 48-week results from VIKING-4, a randomized study. Antivir Ther. 2015;20(3):343-8. doi: 10.3851/IMP2878. Epub 2014 Oct 16.

Results Reference

derived

Learn more about this trial

Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir

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Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir (VIKING-4)

HIV Infections

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial