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HIVPhase 3LIVINGNCT02346487

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

A Phase 3 study testing LPV/RTV pellets and AZT/3TC or ABC/3TC in people with HIV, run by Drugs for Neglected Diseases at 11 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
Conditions the study is for
HIV
What is being tested?
LPV/RTV pellets and AZT/3TC or ABC/3TC
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,003 participants
Where
11 sitesin 3 countries
Study dates
Sep 2015to 14 May 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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,
Show all 14Show fewer
  • 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:
  • ARV naïve, or
  • Already on first line liquid lopinavir based treatment, or
  • 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)

Who cannot join

  • 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.

Trial locations and contacts

11 sites in 3 countries.

11 sites in 3 countries

Uganda5 sites

  • Joint Clinical research Centre

    Fort Portal

  • Joint Clinical Research Centre

    Gulu

  • Baylor College of Medicine, Children's Foundation - Uganda

    Kampala

  • Joint Clinical research Centre

    Kampala

  • Epicentre Mbarara Research Centre

    Mbarara

Other trials in Uganda

Kenya4 sites

  • AMPATH - Moi Teaching and Referral Hospital

    Eldoret

  • FACES Lumumba Clinic

    Kisumu

  • Gertrude's Children Hospital

    Nairobi

  • Kenyatta National Hospital

    Nairobi

Other trials in Kenya

Tanzania2 sites

  • Management and Development for Health(MDH) , at Temeke and Amana Hospitals

    Dar es Salaam

  • Ifakara health Institute

    Morogoro

Other trials in Tanzania

About this study

Official title: Prospective Study of Lopinavir Based ART for HIV Infected childreN Globally

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.

Read the 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.
Conditions
HIV
Being tested
LPV/RTV pellets and AZT/3TC or ABC/3TC
Keywords
children

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LPV/RTV pellets and AZT/3TC or ABC/3TCDrug

    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
Study groups in NCT02346487
Study groupRoleWhat they receive
LPV/RTV pellets and AZT/3TC or ABC/3TCExperimentalOnly 1 arm. No comparator
Receives: Drug: LPV/RTV pellets and AZT/3TC or ABC/3TC

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    • 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

    Measured: 48 weeks

Secondary outcomes (6)

  1. Treatment effectiveness based on virologic, immunologic and clinical endpoints

    • 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

    Measured: 96 weeks

  2. Rate of AEs/SAEs as measure of safety

    • 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…)

    Measured: 96 weeks

  3. Pharmacokinetics - Plasma AUC

    • 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

    Measured: 96 weeks

  4. Feasibility and acceptability questionnaires

    • Questionnaire on Acceptability by caregivers and children of the new LPV based formulation , in particular taste, ease of swallowing, ease of administration, adherence

    Measured: 96 weeks

  5. Pharmacokinetics - Tmax

    • 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

    Measured: 96 weeks

  6. Pharmacokinetics - C12/Cmin

    • 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

    Measured: 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2015 (estimated)
  2. Study startSep 2015
  3. Primary completion14 May 2019
  4. Study completion14 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1,003 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02346487
Sponsor's protocol ID
DNDiHIVPed002
Acronym
LIVING
Status last verified
May 2019
First submitted
13 Jan 2015
Last updated
20 May 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Chupradit S, Wamalwa DC, Maleche-Obimbo E, Kekitiinwa AR, Mwanga-Amumpaire J, Bukusi EA, Nyandiko WM, Mbuthia JK, Swanson A; DNDi Clinical Team; Cressey TR, Punyawudho B, Musiime V; LIVING Study Team. Population Pharmacokinetics of Pediatric Lopinavir/Ritonavir Oral Pellets in Children Living with HIV in Africa. Clin Pharmacol Ther. 2024 May;115(5):1105-1113. doi: 10.1002/cpt.3174. Epub 2024 Jan 21.

    PubMed 38247190

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LPV/RTV pellets and AZT/3TC or ABC/3TC in people with HIV, run by Drugs for Neglected Diseases at 11 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in Uganda, Kenya, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02346487, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2019.

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