A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.

NCT01328041 | Completed Phase 3 Results DMC

• 1 other identifier: 112574
• Study Type: interventional
• Target: 183
• Locations: 7 countries
• Sites: 89

Brief Summary

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.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

GSK1349572; resistance to raltegravir or elvitegravir; Integrase inhibitor; ART-experienced; dolutegravir

Outcome Measures

Primary Outcomes (7)

• Mean Change From Baseline in Plasma HIV-1 RNA at Day 8

  Mean change from Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 8 was calculated as the Day 8 value minus the Baseline value. The last observation was carried forward if a participant had missed the Day 8 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 8. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 8.

  Baseline and Day 8

• Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 24

  The number of participants who had viral load \<50 copies/mL at Week 24 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.

  Week 24

• Number of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48

  The number of participants who had viral load \<50 copies/mL at Week 48 based on the Food and Drug Administration's Snapshot algorithm was assessed. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI \[due to missing data/discontinuation of investigational product prior to the visit window\]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.

  Week 48

• Number of Participants With Any Adverse Event (AE) or Any Serious Adverse Event (SAE)

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.

  From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)

• Number of Participants With Adverse Events of the Indicated Severity, Per the Division of Acquired Immune Deficiency Syndrome (DAIDS) Grading Scale

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An 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, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. AE/SAE severity was graded according to the DAIDS grading scale. The DAIDS displays events as Grades 1-4 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, potentially life threatening.

  From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)

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

  The severity of clinical chemistry toxicities was graded according to the DAIDS toxicity scale. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.

  From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)

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

  The severity of hematology toxicities was graded according to the DAIDS. The DAIDS displays events as Grades 1-5 based on this general guideline: Grade (G) 1, mild; G2, moderate; G3, severe; G4, life threatening; G5, death related to toxicity.

  From the day of the first dose of study drug until end of treatment visit for each participant, up to Week 180 (median of 758 days)

Secondary Outcomes (12)

• Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL at Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48

  Baseline; Day 8; and Weeks 4, 8, 12, 16, 24, 32, 40, and 48

• Number of Participants With Plasma HIV-1 RNA Less Than 400 and 50 Copies/mL From Week 48 Every 12 Weeks up to Study Completion

  From Week 48 every 12 weeks up to study completion.

• Mean Change From Baseline in Plasma HIV-1 RNA at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study Completion

  Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks up to Study completion (Up to Week 180)

• Absolute Values for CD4+ Cell Counts at Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48 and for CD8+ Cell Counts at Baseline and Weeks 4, 12, 24, and 48

  Baseline, Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and 48

• Median Change From Baseline in CD4+ Cell Counts at Day 8 and Weeks 4, 8, 12, 16, 24, 32, 40, and From Week 48 Every 12 Weeks Until Study Completion

  Baseline; Day 8; Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168 and 180. v

Study Arms (1)

dolutegravir

EXPERIMENTAL

dolutegravir plus background antiretroviral therapy optimised at Day 8

Drug: dolutegravir

Interventions

dolutegravir DRUG

50 mg twice daily

dolutegravir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• Shionogi: collaborator
• GlaxoSmithKline: collaborator

Study Sites (89)

GSK Investigational Site

Beverly Hills, California, 90211, United States

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GSK Investigational Site

Fountain Valley, California, 92708, United States

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GSK Investigational Site

Los Angeles, California, 90033, United States

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GSK Investigational Site

Los Angeles, California, 90069, United States

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GSK Investigational Site

San Diego, California, 92103-8208, United States

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GSK Investigational Site

San Francisco, California, 94109, United States

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GSK Investigational Site

New Haven, Connecticut, 06510, United States

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GSK Investigational Site

Norwalk, Connecticut, 06850, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

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GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

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GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

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GSK Investigational Site

Miami Beach, Florida, 33139, United States

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GSK Investigational Site

Orlando, Florida, 32804, United States

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GSK Investigational Site

Atlanta, Georgia, 30308, United States

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GSK Investigational Site

Augusta, Georgia, 30912, United States

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GSK Investigational Site

Lafayette, Louisiana, 70506, United States

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GSK Investigational Site

Boston, Massachusetts, 02115, United States

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GSK Investigational Site

Jackson, Mississippi, 39216-4505, United States

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GSK Investigational Site

Las Vegas, Nevada, 89106, United States

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GSK Investigational Site

Newark, New Jersey, 07103, United States

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GSK Investigational Site

Albany, New York, 12209, United States

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GSK Investigational Site

Buffalo, New York, 14215, United States

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GSK Investigational Site

New York, New York, 10011, United States

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GSK Investigational Site

New York, New York, 10016, United States

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GSK Investigational Site

The Bronx, New York, 10461, United States

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GSK Investigational Site

The Bronx, New York, 10467, United States

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GSK Investigational Site

Valhalla, New York, 10595, United States

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GSK Investigational Site

Chapel Hill, North Carolina, 27599, United States

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GSK Investigational Site

Durham, North Carolina, 27710, United States

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GSK Investigational Site

Toledo, Ohio, 43614, United States

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GSK Investigational Site

Portland, Oregon, 97210, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

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GSK Investigational Site

Providence, Rhode Island, 02906, United States

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GSK Investigational Site

Austin, Texas, 78705, United States

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GSK Investigational Site

Dallas, Texas, 75204, United States

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GSK Investigational Site

Dallas, Texas, 75246, United States

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GSK Investigational Site

Houston, Texas, 77004, United States

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GSK Investigational Site

Houston, Texas, 77098, United States

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GSK Investigational Site

Annandale, Virginia, 22003, United States

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GSK Investigational Site

Seattle, Washington, 98104, United States

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GSK Investigational Site

Brussels, 1000, Belgium

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GSK Investigational Site

Liège, 4000, Belgium

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GSK Investigational Site

Vancouver, British Columbia, V6Z 1Y6, Canada

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GSK Investigational Site

Vancouver, British Columbia, V6Z 2C7, Canada

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GSK Investigational Site

Hamilton, Ontario, L8N 3Z5, Canada

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GSK Investigational Site

Toronto, Ontario, M4N 3M5, Canada

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GSK Investigational Site

Toronto, Ontario, M4T 3A7, Canada

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GSK Investigational Site

Toronto, Ontario, M5B 1L6, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 4P9, Canada

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GSK Investigational Site

Montreal, Quebec, H2L 5B1, Canada

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GSK Investigational Site

Montreal, Quebec, H2W 1T8, Canada

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GSK Investigational Site

Montreal, Quebec, H2X 2P4, Canada

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GSK Investigational Site

Montreal, Quebec, H3G 1A4, Canada

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GSK Investigational Site

Aulnay-sous-Bois, 93602, France

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GSK Investigational Site

Bobigny, 93009, France

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GSK Investigational Site

Bordeaux, 33000, France

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GSK Investigational Site

Garches, 92380, France

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GSK Investigational Site

Gonesse, 95503, France

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GSK Investigational Site

Marseille, 13003, France

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GSK Investigational Site

Marseille, 13009, France

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GSK Investigational Site

Nice, 06202, France

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GSK Investigational Site

Orléans, 45067, France

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GSK Investigational Site

Paris, 75018, France

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GSK Investigational Site

Paris, 75475, France

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GSK Investigational Site

Paris, 75651, France

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GSK Investigational Site

Paris, 75679, France

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GSK Investigational Site

Paris, 75743, France

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GSK Investigational Site

Paris, 75970, France

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GSK Investigational Site

Genoa, Liguria, 16138, Italy

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GSK Investigational Site

Bergamo, Lombardy, 24127, Italy

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GSK Investigational Site

Milan, Lombardy, 20127, Italy

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GSK Investigational Site

Turin, Piedmont, 10149, Italy

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GSK Investigational Site

Bagno A Ripoli (FI), Tuscany, 50011, Italy

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GSK Investigational Site

Florence, Tuscany, 50134, Italy

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GSK Investigational Site

Amadora, Portugal

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GSK Investigational Site

Coimbra, 3030, Portugal

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GSK Investigational Site

Lisbon, 1150, Portugal

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GSK Investigational Site

Lisbon, 1349-019, Portugal

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GSK Investigational Site

Lisbon, 1649-035, Portugal

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GSK Investigational Site

A Coruña, 15006, Spain

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GSK Investigational Site

Alicante, 03010, Spain

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Madrid, 28029, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Seville, 41013, Spain

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Related Publications (2)

• Eron JJ, Clotet B, Durant J, Katlama C, Kumar P, Lazzarin A, Poizot-Martin I, Richmond G, Soriano V, Ait-Khaled M, Fujiwara T, Huang J, Min S, Vavro C, Yeo J; VIKING Study Group. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study. J Infect Dis. 2013 Mar 1;207(5):740-8. doi: 10.1093/infdis/jis750. Epub 2012 Dec 7.

  PMID: 23225901 BACKGROUND

• Castagna A, Maggiolo F, Penco G, Wright D, Mills A, Grossberg R, Molina JM, Chas J, Durant J, Moreno S, Doroana M, Ait-Khaled M, Huang J, Min S, Song I, Vavro C, Nichols G, Yeo JM; VIKING-3 Study Group. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study. J Infect Dis. 2014 Aug 1;210(3):354-62. doi: 10.1093/infdis/jiu051. Epub 2014 Jan 19.

  PMID: 24446523 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2011
• First Posted: April 4, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2015
• Last Updated: January 7, 2016
• Results First Posted: July 21, 2014

Record last verified: 2015-12

Locations

BE (2); CA (11); IT (6); FR (15); US (42); PT (5); ES (8)