A Study of a Nucleoside Sparing Regimen in HIV-1 Infected Patients With Detectable Viremia

NCT02542852 | Completed Phase 2

• 1 other identifier: Dolatav Study
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Research ipotesis is to assess the efficacy and safety of a nucleos(t)ide sparing regimen of atazanavir/ritonavir 300 mg /100 mg QD + Dolutegravir 50 mg QD for the management of virological failure in HIV-1 infected patients. The Primary Objective is to explore the 24-week efficacy of a nucleos(t)ide sparing regimen of atazanavir 300 mg QD/ ritonavir 100 mg QD + Dolutegravir 50 mg QD for the management of virologic failure in HIV-1 infected, integrase inhibitor-naïve subjects.

Conditions

HIV-1 Infection

Keywords

HIV-1

Outcome Measures

Primary Outcomes (1)

• Primary endpoint - The proportion of patients with undetectable HIV RNA viral load ( < 50 copies/ml) at week 24

  The proportion of patients with undetectable HIV RNA viral load ( \< 50 copies/ml) at week 24.

  24 weeks

Secondary Outcomes (9)

• proportion of patient with undetactable HIV RNA at week 4 (Virologic efficacy)

  4 week

• Change from baseline CD4 cell counts (Immunological efficacy)

  4,8,12,16,24 weeks

• Time to achieve undetectability (Virologic efficacy)

  Day 8, weeks 4,8,12,16,24

• Occurrence of genotyping resistance mutations for PI and INSTI in isolates from patients with virological failure.

  24 week

• Atazanavir and Dolutegravir Ctrough (PK evaluation)

  Day 8, weeks 4,8,12,16,24

Study Arms (1)

Open label single arm

EXPERIMENTAL

Introduction of treatment regimen with atazanavir 300mg qd + ritonavir 100mg qd + dolutegravir 50mg qd

Drug: atazanavir 300 mg + ritonavir 100 mg + dolutegravir 50 mg

Interventions

atazanavir 300 mg + ritonavir 100 mg + dolutegravir 50 mg DRUG

Switch to single arm treatment atazanavir-ritonavir 300-100 mg + dolutegravir 50 mg therapy for 24 weeks

Also known as: Reyataz 300 mg + norvir 100 mg + tivicay 50 mg

Open label single arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with age more than 18 years
• Willing and able to provide informed consent
• Failing a stable (at least 3 months) antiretroviral therapy (HIV-RNA more than 200 copies/ml)
• Any CD4 cell count
• Virus susceptible to atazanavir, defined as a genotypic mutation score inferior to 15 according to the HIV drug resistance database (Stanford University)
• No previous documented virologic failure during an atazanavir-containing regimen
• No previous exposure to integrase inhibitors
• Absolute neutrophil count (ANC) more than 500/mm3
• Haemoglobin more than 8.0 g/dL
• Platelet count more than 60,000/mm3
• e-GFR\> 60 ml/min using CKD-EPI equation

You may not qualify if:

• Active AIDS-defining condition at Screening
• Serious illness requiring systemic treatment and/or hospitalization
• Current use of immunomodulant or immunosuppressive drugs
• Requirement for any concomitant medications that are prohibited with any study drugs (protocol section 3.6)
• History or presence of hypersensitivity to any of the active substances or to the excipients
• Alanine aminotransferase (ALT) more than 5 times the upper limit of normal (ULN), OR ALT more than 3xULN and bilirubin more than 1.5xULN (with more than 35 percent direct bilirubin)
• Subjects positive for Hepatitis B at screening (HBsAg positive)
• Subjects with anticipated need for Hepatitis C virus (HCV) therapy during the study
• Presence of moderate or severe hepatic impairment (defined as a Class B or C at Child Pugh Classification) or presence of unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice) or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Pregnancy or pregnancy wish; breastfeeding

Sponsors & Collaborators

• Castagna Antonella: lead
• Bristol-Myers Squibb: collaborator
• ViiV Healthcare: collaborator

Study Sites (1)

Ospedale San Raffaele Scientific Institute

Milan, 20127, Italy

Location

Related Publications (8)

• 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

• Rathbun RC, Lockhart SM, Miller MM, Liedtke MD. Dolutegravir, a second-generation integrase inhibitor for the treatment of HIV-1 infection. Ann Pharmacother. 2014 Mar;48(3):395-403. doi: 10.1177/1060028013513558. Epub 2013 Nov 19.

  PMID: 24259658 BACKGROUND

• Kozal MJ, Lupo S, DeJesus E, Molina JM, McDonald C, Raffi F, Benetucci J, Mancini M, Yang R, Wirtz V, Percival L, Zhang J, Zhu L, Arikan D, Farajallah A, Nguyen BY, Leavitt R, McGrath D, Lataillade M, The Spartan Study Team. A nucleoside- and ritonavir-sparing regimen containing atazanavir plus raltegravir in antiretroviral treatment-naive HIV-infected patients: SPARTAN study results. HIV Clin Trials. 2012 May-Jun;13(3):119-30. doi: 10.1310/hct1303-119.

  PMID: 22592092 BACKGROUND

• Song I, Borland J, Chen S, Lou Y, Peppercorn A, Wajima T, Min S, Piscitelli SC. Effect of atazanavir and atazanavir/ritonavir on the pharmacokinetics of the next-generation HIV integrase inhibitor, S/GSK1349572. Br J Clin Pharmacol. 2011 Jul;72(1):103-8. doi: 10.1111/j.1365-2125.2011.03947.x.

  PMID: 21342217 BACKGROUND

• Molina JM, Lamarca A, Andrade-Villanueva J, Clotet B, Clumeck N, Liu YP, Zhong L, Margot N, Cheng AK, Chuck SL; Study 145 Team. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis. 2012 Jan;12(1):27-35. doi: 10.1016/S1473-3099(11)70249-3. Epub 2011 Oct 18.

  PMID: 22015077 BACKGROUND

• SECOND-LINE Study Group; Boyd MA, Kumarasamy N, Moore CL, Nwizu C, Losso MH, Mohapi L, Martin A, Kerr S, Sohn AH, Teppler H, Van de Steen O, Molina JM, Emery S, Cooper DA. Ritonavir-boosted lopinavir plus nucleoside or nucleotide reverse transcriptase inhibitors versus ritonavir-boosted lopinavir plus raltegravir for treatment of HIV-1 infection in adults with virological failure of a standard first-line ART regimen (SECOND-LINE): a randomised, open-label, non-inferiority study. Lancet. 2013 Jun 15;381(9883):2091-9. doi: 10.1016/S0140-6736(13)61164-2.

  PMID: 23769235 BACKGROUND

• Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S; extended SAILING Study Team. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3.

  PMID: 23830355 RESULT

• 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 RESULT

MeSH Terms

Interventions

Atazanavir Sulfate; Ritonavir; dolutegravir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• Adriano Lazzarin, Prof

  Ospedale San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sub Investigator

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: September 7, 2015
• Study Start: September 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2017
• Last Updated: February 13, 2024

Record last verified: 2024-02

Locations

IT (1)