SMILE: Strategy for Maintenance of HIV suppression with dolutegravir + darunavir/ritonavir in children (PENTA 17)

• Register: ISRCTN
• Last refreshed on: 26 June 2023
• Main ID: ISRCTN11193709
• Date of registration: 06/03/2015
• Prospective Registration: Yes
• Primary sponsor: PENTA Foundation
• Public title: SMILE: Strategy for Maintenance of HIV suppression with dolutegravir + darunavir/ritonavir in children (PENTA 17)
• Scientific 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.
• Date of first enrolment: 01/09/2015
• Target sample size: 300
• Recruitment status: Completed
• URL: https://www.isrctn.com/ISRCTN11193709
• Study type: Interventional
• Study design: A two arm parallel group, non-inferiority, open-label, multi-centre, randomised controlled trial. (Treatment)
• Phase: Phase II/III

Countries of recruitment

Argentina, Belgium, Brazil, Denmark, England, France, Germany, Greece, Ireland, Italy, Mexico, Netherlands, Poland, Portugal, Romania, South Africa, Spain, Sweden, Switzerland, Thailand, Uganda, United Kingdom

Contacts

• Name: Luigi Comacchio

Key inclusion & exclusion criteria

Inclusion criteria: 1. HIV-1 infected children weighing = 17 kg at the screening visit
2. Aged 6 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 load <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 6 months.
6. Children/parents/guardians prepared to switch if randomised to elvitegravir + darunavir/ritonavir 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. For children aged 6-12 either:
8.1. Children and caregivers are willing to participate in the lead-in PK study if the child is aged 6-12 and the PK study is still enrolling children in their weight band* OR
8.2. Data from the lead-in PK study have been analysed and children aged 6-12 can be enrolled directly into the main study

* only children randomised to Arm 1 will take part
Exclusion criteria: 1. Receiving or requiring agents with interactions with darunavir, RTV, or EVG
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. History of previous encephalopathy
5. Intercurrent illness (randomisation can take place after the illness resolves)
6. Creatinine, AST or ALT of grade 3 or above at screening.
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

HIV infection
Infections and Infestations

Intervention(s)

Current intervention as of 06/08/2019:
Eligible participants will be randomised in a 1:1 ratio to switch to once daily INSTI + DRV/r or continue triple therapy. Randomisation will be stratified by age (6 to <12 years, 12 to <18 years) and region (African sites vs non-African sites) using permuted blocks of randomly varying sizes.The once-daily INSTI to be used is dolutegravir. Children weighing 40 kg or more will receive 800 mg darunavir, 100 mg ritonavir and 50 mg dolutegravir.

Previous intervention:
Arm 1: NRTI-sparing regimen - elvitegravir (EVG) + darunavir/ritonavir (DRV/r)
Arm 2: Standard of care (triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI)

Primary Outcome(s)

Percentage of patients with HIV-1 RNA ever =50 copies/ml (confirmed within 4 weeks) at any time up to week 48

Secondary Outcome(s)

Percentage of patients with HIV-1 RNA ever = 50 c/mL (confirmed within 4 weeks) at any time up to week 48
1. Percentage of patients with HIV-1 RNA < 50 c/mL at week 48
2. Percentage of patients with HIV-1 RNA = 50 c/mL at week 24
3. Percentage of patients withHIV-1 RNA = 400c/mL at week 24 and week 48
4. All grade 3 or 4 clinical adverse events (particularly lipodystrophy)
5. All grade 3 or 4 laboratory adverse events
6. Any adverse event at least possibly related to study drugs or leading to treatment modifications
7. Occurrence of new resistance mutations
8. Changes in CD4 (absolute and percentage) from baseline to weeks 24 and 48
9. Change in ART (defined as any change from the ART regimen at randomisation)
10. New or recurrent CDC/WHO stage C or severe stage B event or death
11. Blood lipids
12. Adherence as measured by questionnaire and visual analogue scale
13. Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
14. Height and weight
15. Tanner scales (in participants aged over 8 years)
16. Date of first menses

Secondary ID(s)

2013-001476-37

PENTA 17

Source(s) of Monetary Support

PENTA Foundation (Italy)

Ethics review

Status:
Approval date:
Contact:

Old ethics approval format; French Ethics Committee - submitted

Results

• Results available: Yes
• Date Completed: 30/09/2020