A Phase III Randomized, Double-blind Study of the Safety and Efficacy of GSK1349572 50 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Both Administered with an Investigator-selected Background Regimen Over 48 Weeks in HIV-1 Infected, Integrase Inhibitor-Naïve, Antiretroviral Therapy-Experienced Adults. - SAILING

• Register: EUCTR
• Last refreshed on: 17 May 2021
• Main ID: EUCTR2009-018001-51-PL
• Date of registration: 31/01/2011
• Prospective Registration: Yes
• Primary sponsor: Viiv Healthcare
• Public title: A Phase III Randomized, Double-blind Study of the Safety and Efficacy of GSK1349572 50 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Both Administered with an Investigator-selected Background Regimen Over 48 Weeks in HIV-1 Infected, Integrase Inhibitor-Naïve, Antiretroviral Therapy-Experienced Adults. - SAILING
• Scientific title: A Phase III Randomized, Double-blind Study of the Safety and Efficacy of GSK1349572 50 mg Once Daily Versus Raltegravir 400 mg Twice Daily, Both Administered with an Investigator-selected Background Regimen Over 48 Weeks in HIV-1 Infected, Integrase Inhibitor-Naïve, Antiretroviral Therapy-Experienced Adults. - SAILING
• Date of first enrolment: 07/06/2011
• Target sample size: 688
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-018001-51
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; Other trial design description: 48 week double blind randomised phase followed by open label phase for subjects receiving GSK1349572; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Other specify the comparator: Isentress (Raltegravir)
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Greece, Hungary, Italy, Netherlands, Poland, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1.HIV-1 infected subjects >18 years of age.
2.A female subject is eligible to enter and participate in the study if she:
a.is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and >45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or,
b.is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy:
•Complete abstinence from intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications.
•Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide).
•Approved hormonal contraception may be administered with GSK1349572 (see the SPM for a listing of examples of approved hormonal contraception).
•Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see the SPM for an example listing of approved IUDs).
•Any other method with published data showing that the expected failure rate is <1% per year.
Any contraception method must be used consistently and in accordance with the approved product label.
All subjects participating in the study should be counseled on safer sexual practices including the use of effective barrier methods (e.g. male condom/spermicide).
3.HIV-1 infection as documented by HIV-1 RNA >400 c/mL at Screening and with at least one consecutive HIV-1 RNA >400 c/mL within the four months prior to Screening (unless the Screening HIV-1 RNA is > 1000 c/mL where no additional plasma HIV-1 RNA assessment is needed). (If an additional HIV-1 RNA within four months prior to Screening is not available, a second HIV-1 RNA must be performed during the Screening period [after the first result is available] to serve as a confirmatory sample.)
4.Has documented resistance (via Screening resistance test) to two or more different classes of antiretroviral agents; genotypic resistance is defined by current [IAS] primary mutations; phenotypic resistance is defined as values greater than lower cut off for agents where available and by a clinical/biological cut off if an upper cut off is not available; entry resistance is defined by an assay which identifies any CXCR4-utilizing virus, e.g. Trofile; T20 resistance is defined as IC50 > susceptibility cutoff in PhenoSense entry assay. Historical resistance tests should be used to aid in selection of background therapy. Note: retests of Screening genotypes/phenotypes/tropism assays are not allowed.
5.Is INI-naïve, defined as no prior exposure to any INI (e.g. RAL, elvitegravir, or GSK1349572).
6.Signed and dated written informed consent is obtained from the subject or the subject’s legal representative prior to screening.
7.For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
Exclusionary medical conditions
1.Screening resistance test result indicates no fully active antiviral agents are available for design of the background regimen.
2.Subject-virus is not evaluable using genotype/phenotype/tropism at Screening (assay data is essential for determination of inclusion and/or background therapy).
3.Women who are breastfeeding.
4.Any evidence of an active Center for Disease and Prevention Control (CDC) Category C disease [CDC, 1993], except cutaneous Kaposi’s sarcoma not requiring systemic therapy or historic or current CD4+ cell count <200 cells/mm3 are not exclusionary.
5.Subjects with moderate to severe hepatic impairment as defined by Child-Pugh classification (see Appendix 11.1).
6.Recent history (<3 months) of upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding.
7.Anticipated need for HCV therapy during the study.
8.History or presence of allergy or intolerance to the study drugs or their components or drugs of their class.
9.History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and study medical monitor for inclusion of the subject.
Exclusionary Treatments prior to Screening or Day 1
10.Treatment with an HIV-1 immunotherapeutic vaccine within 90 days prior to Screening.
11.Treatment with any of the following agents within 28 days of Screening:
•radiation therapy,
•cytotoxic chemotherapeutic agents,
•any immunomodulator.
12.Treatment with any agent, other than licensed ART, which has documented activity against HIV-1 in vitro within 28 days of first dose of IP administration.
13.Exposure to an experimental drug and/or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the experimental test agent - whichever is longer, prior to the first dose of IP.
14.French subjects recruited at sites in France will be excluded if the subject has participated in any study using an investigational drug and/or vaccine within 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine – whichever is longer - prior to screening for the study or the subject plans to participate simultaneously in another clinical study.
Exclusionary Lab Values or Clinical Assessments at Screening
15.Any verified Grade 4 laboratory abnormality (a single repeat test is allowed during the Screening period to verify a Grade 4 result). Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject’s participation in the study of an investigational compound is exclusionary.
16.Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN).
17.ALT > 3xULN and bilirubin > 1.5xULN (with >35% direct bilirubin).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

HIV-1 infection
MedDRA version: 14.0 Level: LLT Classification code 10008922 Term: Chronic infection with HIV System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: GSK1349572
Pharmaceutical Form: Film-coated tablet
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Trade Name: ISENTRESS® 400 mg film-coated tablets
Product Name: Raltegravir
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RALTEGRAVIR
CAS Number: 518048-05-0
Other descriptive name: Raltegravir
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 400-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To demonstrate the antiviral efficacy of GSK1349572 50 mg once daily compared to RAL 400 mg BID both in combination with a background regimen consisting of one to two (1-2) fully active single agents in HIV-1 infected, integrase inhibitor-naïve, therapy-experienced subjects at 48 weeks.

Secondary Objective: •To demonstrate antiviral efficacy of GSK1349572 50 mg once daily compared to RAL 400 mg BID both in combination with a background regimen consisting of one to two fully active single agents in HIV-1 infected, integrase inhibitor-naïve, therapy-experienced subjects at 24 weeks.
•To compare the tolerability, long-term safety, antiviral efficacy, and immunologic activity of GSK1349572 50 mg once daily to RAL 400 mg BID, both in combination with a background regimen, over time.
•To assess the development of viral resistance in subjects experiencing virological failure.
•To characterize the PK of GSK1349572 using sparse PK sampling strategy and population-modeling approach.
•To explore exposure-response relationships (e.g., the relationship between GSK1349572 plasma exposure and virologic response or occurrence of AEs) over time.
For remaining secondary objectives please see: page 21 of Protocol.

Primary end point(s): The primary endpoint for this study is the proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using a Missing, Switch, or Discontinuation = Failure (MSDF) algorithm as codified by the FDA’s “snapshot” algorithm (see Section 8.3.2 of Protocol).

Secondary ID(s)

2009-018001-51-ES

ING111762

Ethics review

Status: Approved
Approval date: 14/02/2011
Contact:

Results

• Results available: Yes
• Date Posted: 18/09/2020
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-018001-51/results