A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen. (VIKING-3)
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Purpose
The purpose of this trial is to assess the antiviral activity and safety of a dolutegravir (DTG) containing regimen in HIV-1 infected, antiretroviral therapy (ART)-experienced adults with current or historical failure on an integrase inhibitor (INI) containing regimen. The study will assess DTG 50mg twice daily administered initially with the current failing ART regimen but then with an optimised background ART regimen (OBR) after Day 7. The first analyses will be conducted after the last subject enrolled has completed 24 weeks. Subjects may remain on study after Week 24.
| Condition | Intervention | Phase |
|---|---|---|
|
Infection, Human Immunodeficiency Virus |
Drug: dolutegravir |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase III Study to Demonstrate the Antiviral Activity and Safety of Dolutegravir in HIV-1 Infected Adult Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen. |
- The mean change from Baseline in plasma HIV-1 RNA at Day 8 [ Time Frame: Baseline and Day 8 ] [ Designated as safety issue: No ]
- The proportion of subjects with HIV-1 RNA <50copies/mL at Week 24 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
- The number of subjects with clinical or laboratory adverse events and the severity of such events over time [ Time Frame: 24 weeks and beyond ] [ Designated as safety issue: No ]
- The proportion of subjects with HIV-RNA <400copies/mL and <50copies/mL over time as well as changes from Baseline in HIV-RNA [ Time Frame: Baseline, Weeks 24, 48 ] [ Designated as safety issue: No ]
- The absolute values and change from baseline in CD4+ and CD8+ cell counts over time [ Time Frame: Baseline and Weeks 24, 48 ] [ Designated as safety issue: No ]
- The incidence of HIV-1 disease progression (AIDS and death) [ Time Frame: Weeks 24, 48 ] [ Designated as safety issue: No ]
- Pharmacokinetic parameters of DTG over time as measured by Area Under the Curve, maximum and minimum concentrations of DTG [ Time Frame: Day 8, Weeks 4, 24 ] [ Designated as safety issue: No ]
- Development of genotypic and phenotypic viral resistance to DTG, raltegravir and other on study ARTs [ Time Frame: throughout the study at time of virological failure and up to Week 48 ] [ Designated as safety issue: No ]
| Enrollment: | 175 |
| Study Start Date: | May 2011 |
| Estimated Study Completion Date: | January 2016 |
| Primary Completion Date: | May 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: dolutegravir
dolutegravir plus background antiretroviral therapy optimised at Day 8
|
Drug: dolutegravir
50 mg twice daily
|
Detailed Description:
ING112574 is a Phase 3, multicentre, open-label, single arm study to assess the antiviral activity and safety of DTG containing regimen in HIV-1 infected ART-experienced adults with historical or current evidence of resistance to RAL or ELV. Initially, a minimum of 100 subjects will be enrolled to receive DTG 50mg twice daily with the current failing regimen for 7 days but with OBR from Day 8. Subjects must also have documented genotypic and/or phenotypic resistance to at least one compound in two or more of the other approved classes of ART but must also be able to include at least one fully active drug in the OBR to be started Day 8. The first data cut will take place after the (approximate) 100th subject enrolled completes the Week 24 visit. Enrollment will continue until a further 50 to 100 subjects have been recruited. All subjects who successfully complete 24 weeks of treatment will continue to have access to DTG until it is locally available as long as they continue to derive clinical benefit.
ViiV Healthcare is the sponsor of this study.
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 ≥500 copies/mL
- ART-experienced, INI-experienced, DTG naïve
- Experienced virological failure on raltegravir (RAL) or elvitegravir (ELV) regimen
- The subject's HIV-1 shows resistance to RAL or ELV at Screening or at prior time point of virological failure on RAL or ELV
- Documented resistance to at least one drug from each of three or more of all approved classes of ART
- 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 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 activity against HIV-1 in vitro within 28 days of first dose of investigational product
- Treatment with etravirine, efavirenz, or nevirapine within 14 days of Day 1(etravirine may be used if coadministered with lopinivir/ritonavir or darunavir/ritonavir)
- Treatment with tipranivir/ritonavir, fosamprenavir, or fosamprenavir/ritonavir within 28 days prior to Screening
- Verified Grade 4 laboratory abnormality 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
Show 65 Study Locations| Study Director: | GSK Clinical Trials | ViiV Healthcare |
More Information
No publications provided
| Responsible Party: | ViiV Healthcare |
| ClinicalTrials.gov Identifier: | NCT01328041 History of Changes |
| Other Study ID Numbers: | 112574 |
| Study First Received: | March 31, 2011 |
| Last Updated: | May 16, 2013 |
| Health Authority: | Italy: AIFA - Italian Ministry of Health Spain: Agencia Española del Medicamento y Productos Sanitarios Portugal: Infarmed - Autoridade Nacional do Medicamento e Produtos de Saúde, I.P. Belgium: Agence Fédérale des Medicaments et des Produits de la Santé United States: Food and Drug Administration Canada: Health Canada France: Agence Française de Sécurité Sanitaire des Produits de Santé |
Keywords provided by ViiV Healthcare:
|
GSK1349572 resistance to raltegravir or elvitegravir Integrase inhibitor ART-experienced 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 Integrase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013