A Pilot Study Assessing the Integrase Inhibitor GSK1349572 in HIV-infected Persons With Virus Resistant to Raltegravir

NCT00950859 | Completed Phase 2 Results

• 1 other identifier: 112961
• Study Type: interventional
• Target: 51
• Locations: 5 countries
• Sites: 26

Brief Summary

Integrase is an enzyme produced by HIV so that the virus can multiply in the human body. GSK1349572 is a new drug in the integrase inhibitor class that prevents the enzyme from working properly and therefore prevents the virus from multiplying. GSK1349572 has shown to be effective against viruses in a short-term monotherapy study in adults with no previous exposure to integrase inhibitors. The purpose of this study is to determine whether GSK1349572 is effective in the treatment of HIV-infected patients who no longer respond to treatment with the approved integrase inhibitor raltegravir and carry viruses with resistance to this drug. The safety and efficacy of GSK1349572 50mg once daily in combination with the background HIV drugs previously administered (unless discontinuation of a particular drug is required) will be assessed over 10 days (functional monotherapy phase), followed by the evaluation of the safety and efficacy of GSK1349572 given with a new optimised background regimen from Day 11 through at least Week 24.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

treatment experienced; HIV Infection; raltegravir resistance; GSK1349572; optimized background regimen; integrase inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved HIV-1 RNA <400 Copies (c)/Milliliter (mL) or at Least 0.7 log10 c/mL Below Their Baseline Value at Day 11

  The number of participants who acheived Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) \<400 c/mL or at least 0.7 log10 c/mL below their Baseline value at Day 11 was assessed. The last observation was carried forward if a participant had missed the Day 11 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 11. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 11.

  Baseline (Day 1) and Day 11

Secondary Outcomes (17)

• Mean Change From Baseline in Plasma HIV-1 RNA at Day 6 to 8, Day 11, Weeks 4, 12, 24, 48, 72, 96, From Week 108 Every 12 Weeks up to Study Completion

  Baseline; Day 6 to 8; Day 11; Weeks 4, 12, 24, 48, 72, 96, from 108 every 12 weeks up to study completion

• Number of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL at Baseline and Weeks 4, 12, 24, 48, 72, and 96: TLOVR Analysis.

  Baseline; Weeks 4, 12, 24, 48, 72, and 96

• Proportion of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL From Week 48 Every 12 Weeks up to Study Completion

  From Week 48 every 12 weeks up to study completion

• Change From Baseline in CD4+ Cell Count at Day 11 and Weeks 4, 12, 24, 48, 72, 96, Week 108 Every 12 Weeks up to Study Completion

  Baseline; Day 11; Weeks 4, 12, 24, 48, 72, 96, from Week 108 every 12 weeks up to study completion

• Cmax, Cmin, and Ctau of DTG

  Day 10

Study Arms (2)

GSK1349572 Cohort I

EXPERIMENTAL

Single Arm, Cohort I

Drug: GSK1349572 (Cohort I)

GSK1349572 Cohort II

EXPERIMENTAL

Single Arm, Cohort II

Drug: GSK1349572 (Cohort II)

Interventions

GSK1349572 (Cohort I) DRUG

50 mg once daily

Also known as: Dolutegravir

GSK1349572 Cohort I

GSK1349572 (Cohort II) DRUG

50 mg twice daily

Also known as: Dolutegravir

GSK1349572 Cohort II

Eligibility Criteria

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

You may qualify if:

• HIV-1 infected male or female adults at least 18 years of age with a plasma HIV-1 RNA \> 1,000 copies/mL at study entry. Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
• ART-experienced (defined as on stable ART for at least the last 2 months) and is either currently experiencing virologic failure to RAL or experienced virologic failure to RAL \> 8 weeks prior to Screening
• Must have documented RAL genotypic resistance on study entry genotype
• Must have documented genotypic or phenotypic resistance to at least one drug from each of three or more of all approved classes of ART
• For Cohort II, Subjects MUST be able to receive at least one fully active drug as part of the Day 11 optimised background regimen
• Willing and able to understand and provide signed and dated written informed consent prior to screening

You may not qualify if:

• Any pre-existing mental, physical, or substance abuse disorder which, which could compromise ability to comply with the protocol or compromise subject safety
• Women who are pregnant or breastfeeding
• An active AIDS-defining condition at the screening visit
• Currently take and/or anticipated need for EFV, NVP, FPV/RTV or TPV/RTV during the study
• Treatment with any of the following medications within 15 days of starting study drug, or anticipated to need, during the course of the study: Etravirine (unless co-administered with LPV/RTV or DRV/RTV), rifampin, rifabutin, phenytoin, phenobarbital, barbiturates, glucocorticoids, modafinil, oxcarbazepine, pioglitazone, troglitazone, carbamazepine, St. Johns wort
• Previous participation in an experimental drug and/or vaccine trial(s) within 30 days or 5 half-lives
• History of ongoing or clinically relevant pancreatitis or hepatitis within the previous 6 months
• Expected to require treatment for HCV infection during the first 24 weeks of the study
• Evidence of cirrhosis with or without hepatitis viral co-infection
• History of upper gastrointestinal bleed and/or active peptic ulcer disease
• Screening haemoglobin \<10g/dL (100g/L)
• Subject suffers from a serious medical condition which could compromise the safety of the subject.
• Any condition that could interfere with the absorption, distribution, metabolism or excretion of the drug or render the subject unable to take oral medication
• Screening lipase 3 times the upper limit of normal (ULN)
• Any acute or Grade 4 laboratory abnormality at screening

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (26)

GSK Investigational Site

Phoenix, Arizona, 85012, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Denver, Colorado, 80220, United States

Location

GSK Investigational Site

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

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33308, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Orlando, Florida, 32804, United States

Location

GSK Investigational Site

Santa Fe, New Mexico, 87505, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H3G 1A4, Canada

Location

GSK Investigational Site

Bordeaux, 33000, France

Location

GSK Investigational Site

Le Kremlin-Bicêtre, 94275, France

Location

GSK Investigational Site

Lyon, 69437, France

Location

GSK Investigational Site

Marseille, 13009, France

Location

GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Nice, 06202, France

Location

GSK Investigational Site

Paris, 75651, France

Location

GSK Investigational Site

Milan, Lombardy, 20127, Italy

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Madrid, 28029, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: August 3, 2009
• Study Start: August 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: January 1, 2015
• Last Updated: December 4, 2015
• Results First Posted: October 21, 2013

Record last verified: 2015-09

Locations

US (12); IT (1); ES (4); CA (2); FR (7)