Study Evaluating the Efficacy of a Reduced Dose Atazanavir in HIV-1-infected Patients

NCT02473328 | Completed Phase 2 DMC

• 1 other identifier: CREPATS 003
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of antiretroviral therapy should be maintaining undetectable plasma viral load, only present condition to prevent the progression of the disease, improve immune restoration and prevent the emergence of viral resistance mutations. In addition to the individual benefit, antiretroviral treatment reduces the transmission of HIV from an infected person to sexual partners. There is to date no alternative strategy to antiretroviral treatment and antiretroviral therapy, even extended, does not allow viral eradication. The need to maintain antiretroviral therapy for life raises the long-term safety concerns of it, even with the latest molecules. Also, one of the key issues in clinical research is whether after reaching undetectable viral load, antiretroviral treatment can be reduced in order to reduce exposure to molecules. Indeed, this treatment of "maintenance" could potentially need a smaller antiviral potency. On the other hand, reduction of antiretroviral treatment reduces costs, an important consideration in light of new global recommendations of treatment for all patients with T-cells CD4 below 500 / mm3. The alleviation of antiretroviral therapy is to either reduce the number of molecules by making monotherapies or dual therapy, or to realize or intermittent treatment is to reduce the doses of molecules such as randomized ENCORE -1 showing the equivalence of a dose of Efavirenz 400mg instead of 600mg in naive patients. Atalow study has the sense to lower the dose of Atazanavir / Ritonavir in combination with two NRTI to reduce exposure to this molecule and its cost while maintaining an undetectable viral load.

Conditions

HIV-1 Infection

Keywords

dose reduction study

Outcome Measures

Primary Outcomes (8)

• Measure of effectiveness assessed by maintaining undetectable plasma HIV viral load (viral load ≤ 50 copies / ml) during the all period of this study of treatment with ATV / r 200/100 mg + 2 NRTIs, for all patients.

  one year

• Measure of safety (adverse events)

  Number of participant with adverse events

  one year

• Measure of tolerability assessed by number of patient interrupting the study treatment for virological failure

  one year

• Measure of effectiveness assessed by number of patient maintaining a target trough plasma concentration of atazanavir associated to efficacy:

  Residual plasma concentrations of ATV / r (Dates and last dose of antiretroviral schedules and the association or not with food ) will be performed at day 0 before changing dose reduction of atazanavir, week 12 and week 24 for all patients.

  one year

• Measure of effectiveness assessed in patient with virological failure number of patient dysplaing HIV strains with mutations associated to treatment resistance

  one year

• Measure of tolerability assessed by number of patient interrupting the study treatment for in tolerance

  one year

• Measure of tolerability assessed by quantification of bilirubinemia

  one year

• Measure of tolerability assessed by quantification of creatininemia

  one year

Study Arms (1)

non comparative open study

EXPERIMENTAL

In patients signed an informed consent and meeting all the eligibility criteria at the time of the run-in (S-4), switch of antiretroviral therapy Atazanavir 300 mg/ritonavir 100 mg once a day to Atazanavir 200 mg/ritonavir 100 mg once a day without changing the combination of 2 NRTIs associated. The administration will be done once a day orally for 48 weeks.

Drug: Atazanavir 200 mg/r

Interventions

Atazanavir 200 mg/r DRUG

1. In patients signed an informed consent and meeting all the eligibility criteria at the time of the run-in (S-4), 2. switch of antiretroviral therapy Atazanavir 300 mg/ritonavir 100 mg once a day to Atazanavir 200 mg/ritonavir 100 mg once a day without changing the combination of 2 NRTIs associated. The administration will be done once a day orally for 48 weeks. The usual recommended dose of atazanavir is 300 mg once daily with 100 mg of ritonavir once daily with food. Ritonavir acts by potentiating the pharmacokinetics of atazanavir.

Also known as: ritonavir 100mg

non comparative open study

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented HIV-1 infection.
• Age ≥ 18 years
• Plasma HIV-RNA level ≤ 50 copies/mL during the last 24 months prior to screening visit (W-4), documented by at least 4 time-points
• Stable antiretroviral treatment with 2 NRTI + ATV/r 300/100 for at least 6 month
• CD4+ lymphocytes \> 300 cells/mm3
• Negative urinary pregnancy test and use of efficient contraception for women of childbearing potential
• Signed informed consent
• Patient affiliated or beneficiary of a national insurance scheme (article L1121-11 of the Public health code) (the Medical aid of State or SOUL is not a national insurance scheme)

You may not qualify if:

• HIV-2 infection.
• Patient with resistant mutation for ATV and/or NRTI used on the available genotypic test
• Concomitant treatment using one or more molecules interacting with hepatic cytochromes
• Ongoing cancer. Patients with cancer considered cured for at least six months may be included.
• Active viral hepatitis C requiring a specific treatment during the 48 weeks of the trial
• hemodialysis patients
• Pregnant women, breastfeeding women or women wishing to be pregnant during the study period
• Patient with a history of non-compliance or irregular follow-up
• Subjects under "Backup justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship
• All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance
• Non-attendance which could impede the trial participation (travel abroad, moving, impending transfer...)

Sponsors & Collaborators

• Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida: lead
• INSERM UMR S 1136: collaborator

Study Sites (1)

DUDOIT Yasmine

Paris, 75013, France

Location

MeSH Terms

Interventions

Atazanavir Sulfate; Ritonavir

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

• Christine Katlama, MD

  Groupe Hospitalier Pitié-Salpêtrière

  PRINCIPAL INVESTIGATOR

• Claudine Duvivier, MD

  Hôpital Necker-Enfants Malades

  PRINCIPAL INVESTIGATOR

• Yazdan Yazdanpanah, MD

  Groupe hospitalier Bichat-Claude Bernard

  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

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 16, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

FR (1)