Efficacy and Safety Study of Darunavir for the Treatment of HIV/AIDS (MANET)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Liverpool
Sponsor:
Collaborators:
Janssen Pharmaceutica
Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS
Yaounde Central Hospital
Information provided by (Responsible Party):
Judith Torimiro, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS
ClinicalTrials.gov Identifier:
NCT02155101
First received: June 2, 2014
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

The aim of this pilot study is to assess the feasibility, efficacy and safety of Darunavir/ritonavir 800/100 mg once daily (DRV/r) monotherapy as a switch-maintenance strategy for patients receiving second-line ART at Yaoundé Central Hospital in Cameroon. HIV-infected adults receiving second-line antiretroviral therapy (ART) for ≥3 months with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus either lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r) will undergo plasma HIV-1 RNA ("viral") load testing. Those with a viral load below 50 copies/ml (<50 cps/ml) will undergo a repeat test ideally 4-6 weeks later (allowed up to 12 weeks); if the viral load is confirmed as <50 cps/ml the patient will be invited to join the randomised phase of the study. Patients (n=150) will be randomised 1:2 to either continue the current triple ART regimen (n=50) or switch to DRV/r monotherapy (n=100). The primary end-point will be viral load suppression <400 cps/ml at week 24; secondary end-points will be viral load suppression <50 cps/ml at week 12 and week 24, safety, tolerability, and emergence of protease inhibitor (PI) drug-resistance. Patients will continue observational follow-up depending on the treatment arm they are randomized to. After week 48, patients will return to local standard of care. Pharmacokinetics (PK) and pharmacogenomics sub-study to correlate plasma concentrations of DRV to outcomes, HIV-1 drug resistance testing sub study to detect mutants archived at the time of first-line ART failure and measuring HIV DNA load will be performed, as well as a cost-effectiveness analysis will test the hypothesis that savings can be achieved by switching to DRV/r monotherapy without affecting quality of care. The primary virological objective is to evaluate efficacy in terms of the percentage of subjects who have plasma HIV-1 RNA levels <400 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r) (FDA Snapshot method).

Study hypothesis:

we propose that maintenance therapy with DRV/r monotherapy is a feasible, effective and safe treatment option for patients receiving second-line ART in Yaoundé.


Condition Intervention Phase
HIV/AIDS
Drug: Darunavir
Drug: ART with 2 NRTIs plus LPV/r (or ATV/r)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Monotherapy in Africa: Evaluation of New Therapy

Resource links provided by NLM:


Further study details as provided by University of Liverpool:

Primary Outcome Measures:
  • HIV-1 RNA viral load [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Percentage of subjects who have plasma HIV-1 RNA levels <400 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r) (FDA Snapshot method).


Secondary Outcome Measures:
  • HIV-1 RNA viral load [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Percentage of subjects who have plasma HIV-1 RNA levels <50 cps/ml after 12 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r), using the FDA "Time to Loss of Virologic Response" method.


Other Outcome Measures:
  • HIV-1 RNA Viral load [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Percentage of subjects who have plasma HIV-1 RNA levels <50 cps/ml after 24 weeks of follow-up following a switch to DRV/r monotherapy versus continuing triple therapy containing 2 NRTIs + LPV/r (or ATV/r), using the FDA "Time to Loss of Virologic Response" method.


Estimated Enrollment: 150
Study Start Date: May 2014
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ART with 2 NRTIs plus LPV/r (or ATV/r)

2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus either lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r).

Following Cameroon AIDS Treatment Guidelines.

Drug: ART with 2 NRTIs plus LPV/r (or ATV/r)
Following the Cameroon AIDS Treatment Guidelines for adults, patients on second line antiretroviral therapy take 2 NRTIs and either protease inhibitor lopinavir/ritonavir or atazanavir/ritonavir.
Other Name: NRTI, lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r)
Experimental: Darunavir

Dosage form: Darunavir (PREZISTA) is a film coated, oval shaped, light orange 19.1mm tablet, debossed with "400 mg" on one side and trimethylene carbonate on the other side.

Darunavir/ritonavir dosage: 800/100mg once daily monotherapy Duration: 48 weeks

Drug: Darunavir
Darunavir (PREZISTA) is a film coated, oval shaped, light orange 19.1mm tablet, debossed with 400 mg on one side and trimethylene carbonate on the other side.
Other Name: PREZISTA

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with documented HIV-1 infection.
  2. Male or female aged > 21 years old.
  3. Subjects receiving ART with 2 NRTIs + LPV/r (or ATV/r) for at least 3 months at the time of Screening 1.
  4. Nadir T lymphocyte cluster of differentiation 4 (CD4) >100 cells/mm3
  5. Plasma HIV-1 RNA <50 copies/ml at Screening 1 confirmed ideally 4-6 weeks later at Screening 2 (two results must be documented; a first result obtained up to 12 weeks earlier will be accepted).
  6. Subjects can comply with the protocol requirements. In particular, subjects should be willing to be followed up at least until week 24 (discontinuation prior to week 24) and for the DRV/r arm up to week 48 (discontinuation after week 24) even if they discontinue randomized treatment.
  7. Subjects who have voluntarily signed and dated the consent form.

Exclusion Criteria:

  1. Clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (liver insufficiency).
  2. Co-infection with hepatitis B (HBsAg positive).
  3. Grade 3 or 4 laboratory abnormality as defined by AIDS, including haemoglobin ≤8mg/dL; platelets ≤50 000/mm3; estimated creatinine clearance ≤60ml/ minute, aspartate aminotransferase; alanine aminotransferase and alkaline phosphatase >3 times the upper limit of normal; and total bilirubin >2.5 times the upper limit of normal; with the following exceptions unless clinical assessment foresees an immediate health risk to the subject:

    • Pre-existing diabetes or asymptomatic glucose grade 3 or 4 elevations.
    • Asymptomatic triglyceride or cholesterol elevations of grade 3 or 4.
  4. Presence of any currently active AIDS defining illness (Category C conditions according to the Centers for Disease Control Classification System for HIV Infection 1993) with the following exceptions:

    • Stable cutaneous Kaposi's Sarcoma (i.e., no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the study.
    • Wasting syndrome due to HIV infection. Note: An AIDS defining illness that is not clinically stabilized for at least 30 days will be considered as currently active.
  5. Pregnant or breastfeeding women.
  6. Active substance abuse, including alcohol or recreational drugs.
  7. Any clinically significant disease (e.g., tuberculosis, cardiac dysfunction, pancreatitis, acute viral infections) or life threatening disease in the previous 14 days, or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study.
  8. Any medical or psychiatric condition which, in the opinion of the investigator, could compromise the subject's safety or adherence to the trial protocol.
  9. Previously demonstrated clinically allergy or hypersensitivity to any of the excipients of the investigational medication (DRV).

    Note: DRV is a sulfonamide. Subjects who have previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and DRV has been identified in subjects participating in phase II trials.

  10. Participation in any other clinical trials that involve administration of antiretrovirals or other drugs within the last 4 weeks and during the participation in this trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02155101

Contacts
Contact: Charles kouanfack, MD, PhD 23771962799 charleskouanfack@yahoo.fr
Contact: Victoire Fokom, MD 23776333402 victoire.fokom@yahoo.fr

Locations
Cameroon
Yaounde Central Hospital Recruiting
Yaounde, Centre, Cameroon, 5777
Contact: Charles Kouanfack, MD, PhD    23771962799    charleskouanfack@yahoo.fr   
Contact: Victoire Fokom, MD    23776333402    victoire.fokom@yahoo.fr   
Principal Investigator: Judith N Torimiro, MSc, PhD         
Sponsors and Collaborators
University of Liverpool
Janssen Pharmaceutica
Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS
Yaounde Central Hospital
Investigators
Principal Investigator: Anna Maria Geretti, MD, PhD University of Liverpool
  More Information

No publications provided

Responsible Party: Judith Torimiro, Senior Scientist, Chantal Biya International Reference Centre for Research on Prevention and Management of HIV/AIDS
ClinicalTrials.gov Identifier: NCT02155101     History of Changes
Other Study ID Numbers: ChantalIRCB
Study First Received: June 2, 2014
Last Updated: July 16, 2014
Health Authority: Cameroon: National Ethics Committee

Keywords provided by University of Liverpool:
Efficacy
Safety
Darunavir
HIV-1 RNA level
Cameroon

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Reverse Transcriptase Inhibitors
Ritonavir
Lopinavir
Atazanavir
Darunavir
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 28, 2014