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

February 9, 2024 updated by: Castagna Antonella

A Pilot Phase II Study of a Nucleoside Sparing Regimen of Dolutegravir + Atazanavir/r in HIV-1 Infected Patients With Detectable Viremia (DOLATAV Study)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study design;

• 24-week prospective, single-arm, monocentric, open label, pilot study Participants will be seen at screening, baseline, day 8 and at week 4, 8, 12, 16, 24.

At each visit the following evaluations will be performed:

  • clinical assessment.
  • routine laboratory tests (hematological tests and clinical chemistry) including hemochromocytometric examination with leukocytic formula, creatinine, creatine kinase, transaminases, phosphorus, calcium, alkaline phosphatase, total and direct bilirubin, gammaGT, uric acid, lactate dehydrogenase, urine analysis, glucose, lipid profile, HIV-RNA and CD4 cell counts.

Additional blood samples will be collected at each visit for storage and further determinations.

During follow-up, at different timepoints, patients will additionally undergo:

  • HbA1c and fasting insulin levels and HOMA-IR determination (baseline, week 12, week 24)
  • Adherence assessment (questionnaire and/or pills counts) at week 4, 12 and 24.
  • ECG (baseline and week 24)

Protocol virologic failure is defined as

  • < 1 log10 decrease in plasma HIV-1 RNA by week 12, with subsequent confirmation, unless plasma HIV-RNA < 200 copies/ml OR
  • a confirmed rebound in plasma HIV-RNA levels ≥ 50 copies/ml after prior confirmed suppression to < 50 copies/ml OR a confirmed plasma increase in HIV-1 RNA levels > 1log10 copies/ml above the nadir value where nadir is ≥ 50 copies/ml OR
  • a plasma HIV-1 RNA level ≥ 50 copies/ml at week 24

Subjects who meet a protocol-defined virologic failure during follow-up will be discontinued from the study.

Patients who suppress HIV-1 RNA < 50 cp/ml before week 24 and have a viral blip ≥ 50 copies/ml at week 24 will undergo a plasma HIV-1 RNA re-test to confirm the virologic failure. At virologic failure subjects will perform genotypic and phenotypic tests and a plasma determination of ATV and DTG Cthrough.

No changes in study treatment are allowed with the exception of ritonavir (RTV) discontinuation in patients with hyperbilirubinemia and/or gastrointestinal adverse events judged as RTV-related by the Investigator. In this case, subjects will remain on study using the regimen ATV 400mg QD + DTG 50mg QD. The discontinuation of RTV will not be considered as treatment failure.

In subjects with plasma HIV-RNA < 50 copies/ml at week 24, the study treatment will be successively provided by Italian National Health system.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Milan, Italy, 20127
        • Ospedale San Raffaele Scientific Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Open label single arm
Introduction of treatment regimen with atazanavir 300mg qd + ritonavir 100mg qd + dolutegravir 50mg qd
Drug: atazanavir 300 mg + ritonavir 100 mg + dolutegravir 50 mg
Switch to single arm treatment atazanavir-ritonavir 300-100 mg + dolutegravir 50 mg therapy for 24 weeks
Other Names:
  • Reyataz 300 mg + norvir 100 mg + tivicay 50 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary endpoint - The proportion of patients with undetectable HIV RNA viral load ( < 50 copies/ml) at week 24
Time Frame: 24 weeks
The proportion of patients with undetectable HIV RNA viral load ( < 50 copies/ml) at week 24.
24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
proportion of patient with undetactable HIV RNA at week 4 (Virologic efficacy)
Time Frame: 4 week
proportion of patient with undetactable HIV RNA at week 4
4 week
Change from baseline CD4 cell counts (Immunological efficacy)
Time Frame: 4,8,12,16,24 weeks
Change from baseline CD4 cell counts
4,8,12,16,24 weeks
Time to achieve undetectability (Virologic efficacy)
Time Frame: Day 8, weeks 4,8,12,16,24
Time to achieve undetectability
Day 8, weeks 4,8,12,16,24
Occurrence of genotyping resistance mutations for PI and INSTI in isolates from patients with virological failure.
Time Frame: 24 week
Occurrence of genotyping resistance mutations for PI and INSTI in isolates from patients with virological failure.
24 week
Atazanavir and Dolutegravir Ctrough (PK evaluation)
Time Frame: Day 8, weeks 4,8,12,16,24
Atazanavir and Dolutegravir Ctrough
Day 8, weeks 4,8,12,16,24
Proportion of patients with adverse events (safety and tolerability).
Time Frame: Day 8, weeks 4,8,12,16,24
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
Changes in lipid, clearance creatinine and glycemic profile from baseline (safety and tolerability)
Time Frame: weeks 4,8,12,16,24
Changes in lipid, clearance creatinine and glycemic profile from baseline
weeks 4,8,12,16,24
Change in ECG parameters (safety and tolerability)
Time Frame: 24 week
Change in ECG parameters
24 week
Adherence evaluation
Time Frame: 8,12,16,24 weeks
Adherence changes since first evaluation using questionnaire
8,12,16,24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Castagna Antonella

Collaborators

Bristol-Myers Squibb
ViiV Healthcare

Investigators

  • Principal Investigator: Adriano Lazzarin, Prof, Ospedale San Raffaele

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

August 3, 2015

First Submitted That Met QC Criteria

September 4, 2015

First Posted (Estimated)

September 7, 2015

Study Record Updates

Last Update Posted (Estimated)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 9, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Dolatav Study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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