Clinical trial NCT02346487: Prospective Study of Lopinavir Based ART for HIV Infected childreN Globally (LIVING Study)
Official title: Prospective Study of Lopinavir Based ART for HIV Infected childreN Globally
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Keywords: children
Lead sponsor: Drugs for Neglected Diseases
Sponsor class: OTHER
Collaborators: name: UNITAID
name: French Development Agency
First posted: 2015-01-27
Enrollment: 1003
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
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
timeFrame: 48 weeks
Secondary outcomes:
measure: Treatment effectiveness based on virologic, immunologic and clinical endpoints
timeFrame: 96 weeks
measure: Rate of AEs/SAEs as measure of safety
timeFrame: 96 weeks
measure: Pharmacokinetics - Plasma AUC
timeFrame: 96 weeks
measure: Feasibility and acceptability questionnaires
timeFrame: 96 weeks
measure: Pharmacokinetics - Tmax
timeFrame: 96 weeks
measure: Pharmacokinetics - C12/Cmin
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Eldoret
country: Kenya
facility: AMPATH - Moi Teaching and Referral Hospital
city: Kisumu
country: Kenya
facility: FACES Lumumba Clinic
city: Nairobi
country: Kenya
facility: Gertrude's Children Hospital
city: Nairobi
country: Kenya
facility: Kenyatta National Hospital
city: Dar es salaam
country: Tanzania
facility: Management and Development for Health(MDH) , at Temeke and Amana Hospitals
city: Morogoro
country: Tanzania
facility: Ifakara health Institute
city: Fort Portal
country: Uganda
facility: Joint Clinical research Centre
city: Gulu
country: Uganda
facility: Joint Clinical Research Centre
city: Kampala
country: Uganda
facility: Baylor College of Medicine, Children's Foundation - Uganda
city: Kampala
country: Uganda
facility: Joint Clinical research Centre
city: Mbarara
country: Uganda
facility: Epicentre Mbarara Research Centre
Study officials:
affiliation: University of Nairobi, P.O Box 19676 00202 Nairobi
name: Dalton Wamalwa, MD
role: PRINCIPAL_INVESTIGATOR
References: