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Prospective Study of Lopinavir Based ART for HIV Infected childreN Globally (LIVING Study) (LIVING)

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ClinicalTrials.gov Identifier: NCT02346487
Recruitment Status : Recruiting
First Posted : January 27, 2015
Last Update Posted : November 11, 2016
Sponsor:
Collaborators:
Information provided by (Responsible Party):

Study Description
Brief Summary:
The study will be carried out to provide supportive clinical data on the feasibility, efficacy, safety, and PK of LPV based therapies in routine treatment setting and will be based on the existing LPV/r pellets which already represent a clear advantage in comparison with the liquid formulation.

Condition or disease Intervention/treatment Phase
HIV Drug: LPV/RTV pellets and AZT/3TC or ABC/3TC Phase 3

Detailed Description:

The primary objective is to evaluate the effectiveness of LPV/r pellets in addition to AZT/3TC (or ABC/3TC) paediatric fixed dose combination (FDCs) tablet under routine treatment conditions in HIV infected infants and young children who cannot swallow tablets.

As secondary objectives:

  • Document the safety of LPV/r pellets and AZT/3TC or ABC/3TC
  • Assess the population pharmacokinetics of LPV/r and NRTIs when administered as LPV/r pellets plus AZT/3TC or ABC/3TC
  • Measure adherence to the new formulation
  • Evaluate children acceptability of the LPV/r pellets and associated dual NRTIs as well as ease of use by the care giver.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3000 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Study of Lopinavir Based ART for HIV Infected childreN Globally
Study Start Date : September 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Lopinavir
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: LPV/RTV pellets and AZT/3TC or ABC/3TC
Only 1 arm. No comparator
Drug: LPV/RTV pellets and AZT/3TC or ABC/3TC

Drug: LPV/r pellets 40/10 mg: orally taken twice a day. Dosage according to patient's weight:

  • Between 3 and 5.9kg: 2 capsules twice a day
  • Between 6 and 9.9kg: 3 capsules twice a day
  • Between 10 and 13.9kg: 4 capsules twice a day
  • Between 14 and 19.9kg: 5 capsules twice a day
  • Between 20 and 24.9kg: 6 capsules twice a day

Drug: NRTIs (AZT/3TC 60/30mg tablet or ABC/3TC 60/30mg tablet). Dosage according to patient's weight:

  • Between 3 and 5.9kg: 1 tablet twice a day
  • Between 6 and 9.9kg: 1.5 tablets twice a day
  • Between 10 and 13.9kg: 2 tablets twice a day
  • Between 14 and 19.9kg: 2.5 tablets twice a day
  • Between 20 and 24.9kg: 3 tablets twice a day


Outcome Measures

Primary Outcome Measures :
  1. Treatment effectiveness at 48 weeks based on a composite endpoint of: i) virologic response <1000 copies/ml ii) being alive and iii) on study drug [ Time Frame: 48 weeks ]
    • Treatment effectiveness at 48 weeks based on a composite endpoint of: i) virologic response <1000 copies/ml ii) being alive and iii) on study drug


Secondary Outcome Measures :
  1. Treatment effectiveness based on virologic, immunologic and clinical endpoints [ Time Frame: 96 weeks ]
    • Viral load suppression <1000 copies/ml (as well as <400 &<50 copies/ml where viral load can be measured on plasma) 48 weeks, 96 weeks, after treatment initiation among children under LPV/r based therapy (i.e. in completers) and at the end of the follow-up
    • Clinical failure at 48 weeks and at the end of follow-up defined as new or recurrent disease progression (WHO AIDS definition), death,
    • Immunologic failure as defined by the presence of any of the following:

      1. CD4 percentage fails to rise by 5 percentiles (or CD4 count fails to rise by at least 50 cells/mm3) during the first year of HAART.
      2. CD4 count drops by more than 50% of the peak achieved on HAART.
      3. Decline below age dependent CD4% or CD4 cells count/ml (WHO thresholds for severe immunodeficiency)
    • Retention on therapy

  2. Rate of AEs/SAEs as measure of safety [ Time Frame: 96 weeks ]
    • Rate of severe adverse events
    • Rate of AE/serious AE leading to treatment discontinuation
    • Rate of targeted AEs for lopinavir/ritonavir as well as NRTIs (examples: GI side effects, liver toxicity, ABC-associated hypersensitivity reaction, ZDV-related anaemia and neutropenia…)

  3. Pharmacokinetics - Plasma AUC [ Time Frame: 96 weeks ]
    • Plasma AUC, Tmax and C12/Cmin upon population PK modelling upon using sparse sampling
    • Exposure to LPV/r & adherence as measured by ARV levels in hair

  4. Feasibility and acceptability questionnaires [ Time Frame: 96 weeks ]
    • Questionnaire on Acceptability by caregivers and children of the new LPV based formulation , in particular taste, ease of swallowing, ease of administration, adherence

  5. Pharmacokinetics - Tmax [ Time Frame: 96 weeks ]
    • Plasma AUC, Tmax and C12/Cmin upon population PK modelling upon using sparse sampling
    • Exposure to LPV/r & adherence as measured by ARV levels in hair

  6. Pharmacokinetics - C12/Cmin [ Time Frame: 96 weeks ]
    • Plasma AUC, Tmax and C12/Cmin upon population PK modelling upon using sparse sampling
    • Exposure to LPV/r & adherence as measured by ARV levels in hair


Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

• Past or current documentation of a confirmed diagnosis of HIV infection defined as two positive assays from two different samples taken at a different date as preferred option.

  • At any age: HIV-1 DNA PCR positivity
  • At any time >4 weeks of age: HIV-1 p24 antigen detection or HIV-1 RNA viral load > 5,000 copies/mL plasma
  • At any age >18 months: HIV-1 antibody reactive on two different manufacturers' licensed rapid tests based on a different antigen preparation and/or different test principal, or repeatedly reactive on a licensed enzyme immune assay (EIA)and confirmed on a second sample by any one of the following assays: rapid test (a third manufacturer), licensed EIA, Western blot, chemi-luminescence assay, or plasma RNA with a viral load > 5,000 copies/mL

One single positive PCR assay result will be acceptable for inclusion of a child less than 18 months in the study Although the 2nd PCR assay would not be performed at the time of treatment initiation/treatment switch,

  • In case the test is RNA PCR viral load), the sample should be taken before treatment initiation and analyzed as soon as possible thereafter,
  • In case the child is already on treatment, the test should be DNA PCR based, the blood sample can be taken while on treatment and the results be made available as soon as possible.
  • ARV treatment eligible children with LPV-based treatment indication* as defined by country-specific guidelines or the WHO pediatric treatment guidelines confirmed by investigator:

    1. ARV naïve, or
    2. Already on first line liquid lopinavir based treatment, or
    3. Failing first line NNRTI based therapy
  • Weight ≥3 and <25 kg at the time of enrolment.
  • Inability to swallow tablets*
  • Parent or legal guardian able and willing to provide written informed consent. *Age is not an inclusion criterion. Children older than 5 years who need a LPV/r based treatment and cannot swallow tablets are eligible. Analysis will be stratified according to study entry point (naïve, first line, failure)

Exclusion criteria

  • Planned or concurrent use of NNRTIs, integrase inhibitors, entry inhibitors, or PIs other than LPV/r.
  • PIs treatment failure with the presence or strong suspicion of a PI resistance mutation.
  • Clinical condition requiring the use of a prohibited medication in association with LPV/r
  • Any clinically significant disease or finding during screening that, in the investigator's opinion, would compromise participation in this study.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02346487


Contacts
Contact: Francois Simon, MSc +41 22 907 77 25 fsimon@dndi.org
Contact: Olawale Salami, MD +254 020 3995024 osalami@dndi.org

Locations
Kenya
AMPATH - Moi Teaching and Referral Hospital Recruiting
Eldoret, Kenya
Contact: Winstone Nyandiko, MD    +254722763832    nyandikom@yahoo.com   
FACES Lumumba Clinic Recruiting
Kisumu, Kenya
Contact: Elizabeth Bukusi, MD    +254733617503    EBukusi@kemri.org   
Contact: Patrick Oyaro, MD    +254721245564    poyaro@kemri-ucsf.org   
Gertrude's Children Hospital Recruiting
Nairobi, Kenya
Contact: Joseph Mbuthia, MD    +254720963887    jmbuthia@africaonline.co.ke   
Kenyatta National Hospital Recruiting
Nairobi, Kenya
Contact: Elizabeth Obimbo, MD    +254722720402    eobimbo@hcc.or.ke   
Uganda
Joint Clinical research Centre Recruiting
Fort Portal, Uganda
Contact: Victor Musiime, MD    +256 772401749    vmusiime@jcrc.org.ug   
Contact: Allan Musinguzi, MD    +256774848012    allmussin2@gmail.com   
Joint Clinical Research Centre Recruiting
Gulu, Uganda
Contact: Victor Musiime, MD    +256 772401749    vmusiime@jcrc.org.ug   
Contact: James Abach, MD    +256705204036    jabach@jcrc.org.ug   
Baylor College of Medicine, Children's Foundation - Uganda Recruiting
Kampala, Uganda
Contact: Adeodata Kekitiinwa, MD    +256772462686    akekitiinwa@baylor-uganda.org   
Joint Clinical research Centre Recruiting
Kampala, Uganda
Contact: Victor Musiime, MD    +256 772401749    vmusiime@jcrc.org.ug   
Contact: Grace Mirember, MD    gmirembe@jcrc.org.ug      
Epicentre Mbarara Research Centre Recruiting
Mbarara, Uganda
Contact: Juliet Mwanga, MD    +256793328748    juliet.mwanga@epicentre.msf.org   
Sponsors and Collaborators
Drugs for Neglected Diseases
UNITAID
French Development Agency
Investigators
Principal Investigator: Dalton Wamalwa, MD University of Nairobi, P.O Box 19676 00202 Nairobi
More Information

Responsible Party: Drugs for Neglected Diseases
ClinicalTrials.gov Identifier: NCT02346487     History of Changes
Other Study ID Numbers: DNDiHIVPed002
First Posted: January 27, 2015    Key Record Dates
Last Update Posted: November 11, 2016
Last Verified: November 2016

Keywords provided by Drugs for Neglected Diseases:
children

Additional relevant MeSH terms:
Lopinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors