Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir (VIKING-4)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Infection, Human Immunodeficiency Virus |
Drug: dolutegravir 50 mg twice daily Drug: dolutegravir placebo twice daily Drug: Open-label dolutegravir 50mg twice daily |
Phase 3 |
Access to an investigational treatment associated with this study is available outside the clinical trial. More info ...
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Phase III Randomized, Double-blind Trial Investigating the Activity of Dolutegravir 50 mg BID vs Placebo Over 7 Days in HIV-1-infected Subjects With RAL/ELV Resistance, Followed by an Open-label Phase With an Optimized Background Regimen |
- Mean change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Day 8 [ Time Frame: Day 8 ] [ Designated as safety issue: No ]Mean change from baseline in plasma HIV-1 RNA (log10 copies/mL) at Day 8 analysis will use a last observation carried forward with discontinuation equals baseline (LOCFDB) dataset.
- Proportion of subjects with HIV-1 RNA <50c/mL and <400c/mL [ Time Frame: Week 24, 48 and beyond ] [ Designated as safety issue: No ]To assess the antiviral activity of DTG over time when administered with optimized background regimen (OBR) consisting of at least one fully active agent from Day 8
- Absolute value and change from baseline in CD4+ and CD8+ cell counts [ Time Frame: Week 24, 48 and beyond ] [ Designated as safety issue: No ]
- Incidence of HIV-1 disease progression [ Time Frame: Week 24, 48 and beyond ] [ Designated as safety issue: No ]
- Number of subjects with clinical and laboratory adverse events and severity of such events overtime [ Time Frame: Week 24, 48 and beyond ] [ Designated as safety issue: No ]
- Pharmacokinetic parameters of DTG as measured by Area Under the Curve, maximum and minimum concentrations of DTG [ Time Frame: Day 8, Day 28 and Week 24 ] [ Designated as safety issue: No ]
- Incidence of treatment emergent viral resistance to DTG, raltegravir and other on study ARTs in subjects experiencing virologic failure [ Time Frame: throughout the study at time of virologic failure ] [ Designated as safety issue: No ]
| Enrollment: | 30 |
| Study Start Date: | April 2012 |
| Estimated Study Completion Date: | June 2015 |
| Primary Completion Date: | October 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: dolutegravir 50mg twice daily
Active dolutegravir plus failing background regimen (Day 1 to Day 7)
|
Drug: dolutegravir 50 mg twice daily
Active dolutegravir plus failing background regimen (Day 1 to Day 7)
Other Name: GSK1349572
|
|
Experimental: dolutegravir placebo twice daily
Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)
|
Drug: dolutegravir placebo twice daily
Dolutegravir placebo plus failing background regimen (Day 1 to Day 7)
Other Name: GSK1349572 Placebo
|
|
Experimental: Open-label dolutegravir 50mg twice daily
Open label dolutegravir plus optimized background regimen (From Day 8)
|
Drug: Open-label dolutegravir 50mg twice daily
Open label dolutegravir plus optimized background regimen (from Day 8)
Other Name: GSK1349572
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, California | |
| GSK Investigational Site | |
| Bakersfield, California, United States, 93301 | |
| GSK Investigational Site | |
| Beverly Hills, California, United States, 90211 | |
| GSK Investigational Site | |
| Los Angeles, California, United States, 90069 | |
| United States, Connecticut | |
| GSK Investigational Site | |
| Norwalk, Connecticut, United States, 06850 | |
| United States, District of Columbia | |
| GSK Investigational Site | |
| Washington, District of Columbia, United States, 20007 | |
| GSK Investigational Site | |
| Washington, District of Columbia, United States, 20009 | |
| United States, Florida | |
| GSK Investigational Site | |
| Fort Lauderdale, Florida, United States, 33316 | |
| GSK Investigational Site | |
| Fort Pierce, Florida, United States, 34982 | |
| GSK Investigational Site | |
| Orlando, Florida, United States, 32803 | |
| United States, Georgia | |
| GSK Investigational Site | |
| Savannah, Georgia, United States, 31401 | |
| United States, Massachusetts | |
| GSK Investigational Site | |
| Boston, Massachusetts, United States, 02115 | |
| United States, New York | |
| GSK Investigational Site | |
| Bronx, New York, United States, 10467 | |
| GSK Investigational Site | |
| Buffalo, New York, United States, 14215 | |
| GSK Investigational Site | |
| New York, New York, United States, 10011 | |
| United States, North Carolina | |
| GSK Investigational Site | |
| Durham, North Carolina, United States, 27710 | |
| United States, Pennsylvania | |
| GSK Investigational Site | |
| Philadelphia, Pennsylvania, United States, 19140 | |
| United States, Texas | |
| GSK Investigational Site | |
| Dallas, Texas, United States, 75246 | |
| United States, Virginia | |
| GSK Investigational Site | |
| Annandale, Virginia, United States, 22003 | |
| Study Director: | GSK Clinical Trials | ViiV Healthcare |
More Information
No publications provided
| Responsible Party: | ViiV Healthcare |
| ClinicalTrials.gov Identifier: | NCT01568892 History of Changes |
| Other Study ID Numbers: | 116529 |
| Study First Received: | March 29, 2012 |
| Last Updated: | May 9, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by ViiV Healthcare:
|
ART-experienced GSK1349572 Integrase inhibitor resistance Dolutegravir |
Additional relevant MeSH terms:
|
Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes Lentivirus Infections Retroviridae Infections RNA Virus Infections |
Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Immune System Diseases |
ClinicalTrials.gov processed this record on May 19, 2013