HIV-1 Infection Clinical Trial
— DolatavOfficial title:
A Pilot Phase II Study of a Nucleoside Sparing Regimen of Dolutegravir + Atazanavir/r in HIV-1 Infected Patients With Detectable Viremia (DOLATAV Study)
Verified date | February 2024 |
Source | IRCCS San Raffaele |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 10 |
Est. completion date | December 2017 |
Est. primary completion date | June 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 70 Years |
Eligibility | Inclusion Criteria: - 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 Exclusion Criteria: - 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 Moreover, all clinical conditions reported as an absolute contraindication in the summary of product characteristics of the study drugs, will be considered as exclusion criteria. |
Country | Name | City | State |
---|---|---|---|
Italy | Ospedale San Raffaele Scientific Institute | Milan |
Lead Sponsor | Collaborator |
---|---|
Castagna Antonella | Bristol-Myers Squibb, ViiV Healthcare |
Italy,
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; — View Citation
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 — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | proportion of patient with undetactable HIV RNA at week 4 (Virologic efficacy) | proportion of patient with undetactable HIV RNA at week 4 | 4 week | |
Secondary | Change from baseline CD4 cell counts (Immunological efficacy) | Change from baseline CD4 cell counts | 4,8,12,16,24 weeks | |
Secondary | Time to achieve undetectability (Virologic efficacy) | Time to achieve undetectability | Day 8, weeks 4,8,12,16,24 | |
Secondary | Occurrence of genotyping resistance mutations for PI and INSTI in isolates from patients with virological failure. | Occurrence of genotyping resistance mutations for PI and INSTI in isolates from patients with virological failure. | 24 week | |
Secondary | Atazanavir and Dolutegravir Ctrough (PK evaluation) | Atazanavir and Dolutegravir Ctrough | Day 8, weeks 4,8,12,16,24 | |
Secondary | Proportion of patients with adverse events (safety and tolerability). | Proportion of patients with adverse events (any grade, proportion of patients with more than or equal than grade 2 AE, proportion of patients with side effects leading to discontinuation, reason for treatment discontinuation. | Day 8, weeks 4,8,12,16,24 | |
Secondary | Changes in lipid, clearance creatinine and glycemic profile from baseline (safety and tolerability) | Changes in lipid, clearance creatinine and glycemic profile from baseline | weeks 4,8,12,16,24 | |
Secondary | Change in ECG parameters (safety and tolerability) | Change in ECG parameters | 24 week | |
Secondary | Adherence evaluation | Adherence changes since first evaluation using questionnaire | 8,12,16,24 weeks |
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