Comparative efficacy and safety study of dolutegravir and lopinavir/ritonavir in second-line treatment

• Register: REBEC
• Last refreshed on: 29 May 2023
• Main ID: RBR-3m6cny
• Date of registration: 22/02/2016
• Prospective Registration: No
• Primary sponsor: ViiV Healthcare
• Public title: Comparative efficacy and safety study of dolutegravir and lopinavir/ritonavir in second-line treatment
• Scientific title: 200304 - A phase 3b,randomised,open-label study of the antiviral activity and safety of dolutegravir compared to lopinavir/ritonavir both administered with dual nucleoside reverse transcriptase inhibitor therapy in HIV-1 (Type I virus of acquired immunodeficiency syndrome) infected adult subjects with treatment failure on first line therapy
• Date of first enrolment: 29/07/2015
• Recruitment status: Recruitment completed
• URL: http://ensaiosclinicos.gov.br/rg/RBR-3m6cny
• Study type: Intervention
• Study design: Clinical Trial for treatment, randomized, controled, pararell, open, two arms, phase 3
• Phase: 3

Countries of recruitment

Argentina, Brazil, Chile, China, Colombia, Kenya, Mexico, Peru, Romania, Russian Federation, South Africa, Thailand, Ukraine

Contacts

• Name: Pesquisador Responsável Contato Científico
• Affiliation: GlaxoSmithKline Brasil

• Name: Pesquisador Responsável - Contato Público
• Affiliation: GlaxoSmithKline Brasil

Key inclusion & exclusion criteria

Inclusion criteria: HIV-1 infected subjects greater or equal to 18 years of age;

A female subject may be eligible to enter and participate in the study if she: is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and greater or equal to 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, is of child-bearing potential, with a negative pregnancy test at both screening and day 1 and agrees to use one of the protocol-defined methods of contraception to avoid pregnancy;

HIV-1 infection as documented by HIV-1 RNA greater or equal than 400 c/mL at screening; subject has been on a first-line treatment regimen consisting of an NNRTI plus two NRTIs for at least 6 months and is currently experiencing virologic failure to this first-line regimen defined as two consecutive (greater or equal to 7 days apart) HIV-1 RNA results of greater or equal to 400 c/mL; subjects must receive at least one fully active agent within the dual-NRTI background regimen for second line treatment; fully active is defined by the screening genotypic resistance report of the central laboratory (or a laboratory contracted by the central laboratory) showing no evidence of full or of partial resistance for a given NRTI which will be taken on study; subject is PI-naïve and Integrase inhibitor (INI)-naïve, defined as no prior or current exposure to any PI or INI; subject or the subject's legal representative is willing and able to understand and provide signed and dated written informed consent prior to screening

Exclusion criteria: Women who are breastfeeding; any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic or current CD4+ cell levels less than 200 cells per cubic millimeter; subjects with severe hepatic impairment, class C, as determined by Child-Pugh classification; unstable liver disease, as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, cirrhosis, known biliary abnormalities, with the exception of Gilbert's syndrome or asymptomatic gallstones; anticipated need for hepatitis C virus, HCV, therapy during the randomised phase of the study; history or presence of allergy or intolerance to the study drugs or their components or drugs of their class; ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localised malignancies require agreement between the investigator and the study medical monitor for inclusion of the subject; subjects who in the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behaviour and/or suicidal ideation may be considered as evidence of serious suicide risk; treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening; treatment with any of the following agents within 28 days of screening: radiation therapy, cytotoxic chemotherapeutic agents, systemically administered immunomodulators; treatment with any agent, other than licensed ART as allowed above with documented activity against HIV-1 in vitro/vivo within 28 days of first dose of investigational product. The exception is use of entecavir, in appropriate clinical situations, for treatment of hepatitis B, e.g. prior intolerance to Tenofovir, viral resistance to lamivudine (3TC)/Emtricitabine (FTC), after discussion and agreement between the investigator and the medical monitor; exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product; any evidence of primary viral resistance to protease inhibitors or integrase inhbitors based on the presence of any major resistance-associated mutation; the subject's virus does not yield results using genotype at screening, assay data is essential for eligibility determination; any verified grade 4 laboratory abnormality, with the exception of grade 4 triglycerides. A single repeat test is allowed during the screening period to verify a 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; alanine aminotransferase, ALT, greater or equal than 5 times the upper limit of normal, ULN, or ALT greater or equal than 3xULN and bilirubin greater or equal than 1.5xULN (with more than 35% direct bilirubin)

Age minimum: 18Y
Age maximum:
Gender: -

Health Condition(s) or Problem(s) studied

C02.782.815.616.400

infection, human immunodeficiency virus

Intervention(s)

It will be included 612 subjects randomized on proportion of 1:1 divided on 2 treatment's arms (306 subjects alocated on arm 1 and 306 subjects alocated on arm 2). Brazil will include 80 subjects.

Arm 1 drug: Subject will receive dolutegarvir oral tablets of 50 mg once daily plus two nucleoside reverse transcriptase inhibitors selected by the study investigator. On Brazil it' will be included 80 subjects.

Arm 2 drug: Subject will receive lopinavir/ritonavir 4 oral tablets 200/50mg once daily or two tablets of 200/50mg lopinavir/ritonavir twice daily plus two nucleoside reverse transcriptase inhibitors selected by the study investigator.

D27.505.519.389.375

Drug

D27.505.519.389.745.420

D27.505.519.389.375.400

Primary Outcome(s)

The proportion of subjects responsive from the randomized subjects that received at least one dose of study medication (intention to treat population):
It will be analize on time frame: 48 week;
Using the Snapshot algorithm of FDA;
Plasma HIV-1 ribonucleic acid (RNA) less than 50 copies per millilitre (c/mL)

The proportion of subjects non responsive:
Subjects with HIV-1 RNA greater or equal than 50 c/mL; Without HIV RNA data at week 48, subjects with background ART substitutions not permitted per protocol and subjects with background ART substitutions permitted per protocol after week 4 but where their last HIV-1 RNA result prior to the date of decision to switch was greater or equal than 50 c/mL

Secondary Outcome(s)

Proportion of subjects with plasma HIV-1 RNA <50 c/mL using the Snapshot algorithm on week 24; Proportion of subjects with plasma HIV-1 RNA <400 c/mL using the Snapshot algorithm on week 24; Proportion of subjects without virologic or tolerability failure by Weeks 24 and 48;Incidence of disease progression;

Source(s) of Monetary Support

GlaxoSmithKline

ViiV Healthcare

Secondary Sponsor(s)

GlaxoSmithKline