A Clinical Research Study for Assessing the Effectiveness of the New Integrase Inhibitor GSK1349572 in HIV-infected Persons With Prior Antiretroviral Treatment and Resistance to Raltegravir - Full Text View

Sponsor:	ViiV Healthcare
Collaborator:	GlaxoSmithKline
Information provided by:	ViiV Healthcare
ClinicalTrials.gov Identifier:	NCT00950859

Purpose

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.

Condition	Intervention	Phase
Infection, Human Immunodeficiency Virus	Drug: GSK1349572 (Cohort I) Drug: GSK1349572 (Cohort II)	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pilot Study to Assess the Antiviral Activity of GSK1349572 Containing Regimen in Antiretroviral Therapy (ART)-Experienced, HIV-1-infected Adult Subjects With Raltegravir Resistance

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Raltegravir Raltegravir potassium

U.S. FDA Resources

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:

HIV viral load [ Time Frame: Day 1 to Day 11 functional monotherapy phase ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

HIV viral load [ Time Frame: Day 11 and Week 24 ] [ Designated as safety issue: No ]
CD4 T-cell count [ Time Frame: Throughout the study up to 24 and 48 weeks ] [ Designated as safety issue: No ]
Pharmacokinetic parameters (GSK1349572 Cmax and Cmin) [ Time Frame: Day 10/11, Week 4 and Week 24 ] [ Designated as safety issue: No ]
Genotypic resistance (treatment emergent mutation in integrase gene) [ Time Frame: Throughout the study at time of virologic failure up to Week 48 ] [ Designated as safety issue: No ]
Incidence and severity of all grades clinical and laboratory adverse event [ Time Frame: Throughout the study up to 24 and 48 weeks ] [ Designated as safety issue: No ]
CD4 T-cell percentage [ Time Frame: Throughout the study up to 24 and 48 weeks ] [ Designated as safety issue: No ]
Pharmacokinetic parameters (GSK1349572 AUC) [ Time Frame: Day 10/11, Week 4 and Week 24 ] [ Designated as safety issue: No ]
Phenotypic resistance (Fold change in GSK1349572 IC50) [ Time Frame: Thoughout the study at time of virologic failure and up to Week 48 ] [ Designated as safety issue: No ]

Enrollment:	51
Study Start Date:	August 2009
Estimated Study Completion Date:	January 2013
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GSK1349572 Cohort I Single Arm, Cohort I	Drug: GSK1349572 (Cohort I) 50 mg once daily
Experimental: GSK1349572 Cohort II Single Arm, Cohort II	Drug: GSK1349572 (Cohort II) 50 mg twice daily

Detailed Description:

Study (ING112961) is a Phase IIb, multicentre, open-label, single arm, two cohorts, pilot study to assess the antiviral activity of GSK1349572 containing regimen in HIV-1 infected ART-experienced adults with raltegravir (RAL) resistance. The study will include approximately 50 ART-experienced subjects with either current or past virologic failure to RAL. All subjects must harbour isolates with RAL resistance mutations at Screening. Subjects should also have documented genotypic and/or phenotypic resistance to at least one compound from each of three or more of the approved classes of ART (including integrase inhibitors [INIs]). Subjects with current RAL virologic failure will substitute RAL with GSK1349572 50mg once daily and continue the remaining components of their failing regimen through Day 10. Subjects with historical RAL virologic failure will add GSK1349572 50mg once daily to their failing regimen through Day 10. On Day 11 all subjects will continue GSK1349572 and optimize their background therapy. Antiviral activity, safety and tolerability of GSK1349572 will be evaluated at Day 11 and over time through at least Week 24.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
Screening alanine aminotransferase (ALT) >5xULN
Screening ALT 3xULN and bilirubin 1.5xULN (with 35% direct bilirubin)
Personal or family history of prolonged QT syndrome.
Any clinically significant finding, as specified in the protocol, on screening or baseline electrocardiograph (ECG)
History of allergy to the study drugs or their components or drugs of their class
Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or future need of treatment with these agents during the study
Treatment with immunomodulators within 28 days prior to screening or subject has received an HIV-1 vaccine within 90 days prior to screening

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950859

Show 26 Study Locations

Sponsors and Collaborators

ViiV Healthcare

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

ViiV Healthcare

More Information

No publications provided

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier:	NCT00950859 History of Changes
Other Study ID Numbers:	112961
Study First Received:	July 23, 2009
Last Updated:	January 5, 2012
Health Authority:	Italy: AIFA - Italian Ministry of Health; Spain: Agencia Española del Medicamento y Productos Sanitarios; Canada: Health Canada; France: Agence Française de Sécurité Sanitaire des Produits de Santé; United States: Food and Drug Administration

Keywords provided by ViiV Healthcare:

treatment experienced
HIV Infection
raltegravir resistance

GSK1349572
optimized background regimen
integrase inhibitor

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 February 09, 2012