Clinical trial NCT02383108: Strategy for Maintenance of HIV Suppression With Once Daily Integrate Inhibitor+Darunavir/Ritonavir in Children
Official title: A Two-arm, Phase 2/3 Multicentre, Open-label, Randomised Study Evaluating Safety and Antiviral Effect of Current Standard Antiretroviral Therapy Compared to Once Daily Integrase Inhibitor Administered With Darunavir/Ritonavir (DRV/r) in HIV-1 Infected, Virologically Suppressed Paediatric Participants.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: HIV Infection
Lead sponsor: PENTA Foundation
Sponsor class: NETWORK
Collaborators: name: Institut National de la Santé Et de la Recherche Médicale, France
name: MRC CTU at UCL
name: PHPT
First posted: 2015-03-09
Enrollment: 318
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A two-arm, Phase 2/3 multicentre, open-label, randomised study evaluating safety and antiviral effect of current standard antiretroviral therapy compared to once daily integrase inhibitor administered with darunavir/ritonavir (DRV/r) in HIV-1 infected, virologically suppressed paediatric participants.

Detailed description: A two arm parallel group, non-inferiority, open-label, multi-centre, randomised controlled trial.

Eligibility criteria: Inclusion Criteria:

1. HIV-1 infected children aged ≥ 12 years old and weighing ≥40kg\* at the screening visit
2. Aged 12 to \< 18 years old\*\*
3. Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
4. Children must have all HIV-1 RNA viral loads \<50c/mL for at least 12 months with a minimum of two separate results before screening.
5. Children on a 3-drug PI/r or NNRTI containing regimen for at least 24 weeks
6. Children/parents/guardians prepared to switch if randomised to once daily integrase inhibitor + DRV/RTV arm
7. Children and parents prepared to restart the current ART regimen after simplification if viral load restart criteria are met (see Section 5.5)
8. Be affiliated or beneficiary to Health Social security scheme (in countries where this is mandatory)

   * Initially enrolment will be of participants ≥ 12 years old and ≥40kg only. DTG 50 mg will be supplied by ViiV Healthcare.

     * As more data become available on younger children, a protocol amendment is planned to include younger children and/or lower weight bands.

Exclusion Criteria:

1. Receiving or requiring agents with interactions with DRV, RTV, or any once daily integrase inhibitor (Appendix 14)
2. Evidence of resistance to DRV or integrase inhibitors (for participants in clinical sites where resistance testing is standard of care)
3. Previous exposure to integrase inhibitors for more than 2 weeks
4. Intercurrent illness (randomisation can take place after the illness resolves)
5. Creatinine ≥ 1.8ULN or ALT ≥ 5ULN or ALT ≥ 3ULN and bilirubin ≥2ULN at screening.
6. Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
7. Diagnosis of tuberculosis and on anti-tuberculosis treatment (children can be enrolled after successful tuberculosis treatment)
8. Hepatitis B or Hepatitis C co-infection
9. Pregnancy or risk of pregnancy in girls of child-bearing potential unless committed to taking effective contraception
10. History or presence of known allergy or some other contraindication to the study drugs or their components as described in the SmPC

Primary outcomes:
measure: Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks)
timeFrame: at any time up to week 48
Secondary outcomes:
measure: Percentage of patients with HIV-1 RNA < 50 c/mL
timeFrame: at week 48
measure: Percentage of patients with HIV-1 RNA ≥ 50 c/mL
timeFrame: at week 24
measure: Percentage of patients withHIV-1 RNA ≥ 400c/mL
timeFrame: at week 24 and week 48
measure: Percentage of patients with any grade 3 or 4 clinical adverse events (particularly lipodystrophy); any grade 3 or 4 laboratory adverse events
timeFrame: over 48 weeks
measure: All grade 3 or 4 laboratory adverse events
timeFrame: over 48 weeks
measure: Any adverse event at least possibly related to study drugs or leading to treatment modifications
timeFrame: over 48 weeks
measure: Occurrence of new resistance mutations
timeFrame: over 48 weeks
measure: Changes in CD4 (absolute and percentage)
timeFrame: from baseline to weeks 24 and 48
measure: Change in ART (defined as any change from the ART regimen at randomisation)
timeFrame: at week 0
measure: New or recurrent CDC/WHO stage C or severe stage B event or death
timeFrame: over 48 weeks
measure: Blood lipids
timeFrame: over 48 weeks
measure: Adherence as measured by questionnaire and visual analogue scale
timeFrame: over 48 weeks
measure: Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
timeFrame: over 48 weeks
measure: Tanner scales (in participants aged over 8 years)
timeFrame: over 48 weeks
measure: Date of first menses
timeFrame: over 48 weeks
measure: Height
timeFrame: Over 48 weeks
measure: Weight
timeFrame: over 48 weeks
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital Garrahan
city: Cannes
country: France
facility: Centre Hospitalier Andrée Rosemon
city: Nantes
country: France
facility: CHU Hôtel Dieu - Nantes
city: Mexico City
country: Mexico
facility: Hospital General Mexico
city: Lisbon
country: Portugal
facility: Hospital de Dona Estefânia - CHLC
city: Porto
country: Portugal
facility: Centro Materno-Infantil de Norte
city: Cape Town
country: South Africa
facility: FAM-CRU
city: Soweto
country: South Africa
facility: PHRU
city: Barcelona
country: Spain
facility: Hospital San Joan de Deu
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital General Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital La Paz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario de Getafe
city: Bern
country: Switzerland
facility: Inselpital Bern
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St Gallen
city: Zürich
country: Switzerland
facility: Kinderspital Zurich
city: Chanthaburi
country: Thailand
facility: Prapokklao Hospital
city: Chiang Mai
country: Thailand
facility: Nakornping Hospital
city: Chiang Rai
country: Thailand
facility: Chiangrai Prachanukroh Hospital
city: Kalasin
country: Thailand
facility: Kalasin hospital
city: Khon Kaen
country: Thailand
facility: Khonkaen hospital
city: Phayao
country: Thailand
facility: Phayao hospital
city: Kampala
country: Uganda
facility: Baylor
city: Mbarara
country: Uganda
facility: JCRC
city: Kiev
country: Ukraine
facility: Kiev
city: Kryvyi Rih
country: Ukraine
facility: Kryvyi Rih
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Bristol
country: United Kingdom
facility: Bristol Hospital
city: London
country: United Kingdom
facility: Evelina Children Hospital, St Thomas's Hospital
city: London
country: United Kingdom
facility: King's College Hospital
Study officials:
References: