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Clinical Trials


Strategy for Maintenance of HIV Suppression With Elvitegravir + Darunavir/Ritonavir in Children (SMILE)

This study is currently recruiting participants. (see Contacts and Locations)

Verified September 2016 by PENTA Foundation

PENTA Foundation

Information provided by (Responsible Party)
PENTA Foundation Identifier

First received: February 19, 2015
Last updated: September 15, 2016
Last Verified: September 2016
History of Changes


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

Condition Intervention Phase
HIV Infection

Drug : EVG +DRV/r
Drug : SOC
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Multicentre, Open-label, Randomised Study Evaluating Safety and Antiviral Effect of Elvitegravir (EVG) Administered With Darunavir/Ritonavir (DRV/r)Compared to Current Standard Antiretroviral Therapy in HIV-1 Infected, Virologically Suppressed Paediatric Participants.

Further study details as provided by PENTA Foundation:

Primary Outcome Measures

  • Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks) [ Time Frame: at any time up to week 48 ]
Secondary Outcome Measures:
  • Percentage of patients with HIV-1 RNA < 50 c/mL [ Time Frame: at week 48 ]
  • Percentage of patients with HIV-1 RNA ≥ 50 c/mL [ Time Frame: at week 24 ]
  • Percentage of patients withHIV-1 RNA ≥ 400c/mL [ Time Frame: at week 24 and week 48 ]
  • All grade 3 or 4 clinical adverse events (particularly lipodystrophy) [ Time Frame: over 48 weeks ]
  • All grade 3 or 4 laboratory adverse events [ Time Frame: over 48 weeks ]
  • Any adverse event at least possibly related to study drugs or leading to treatment modifications [ Time Frame: over 48 weeks ]
  • Occurrence of new resistance mutations [ Time Frame: over 48 weeks ]
  • Changes in CD4 (absolute and percentage) [ Time Frame: from baseline to weeks 24 and 48 ]
  • Change in ART (defined as any change from the ART regimen at randomisation) [ Time Frame: at week 0 ]
  • New or recurrent CDC/WHO stage C or severe stage B event or death [ Time Frame: over 48 weeks ]
  • Blood lipids [ Time Frame: over 48 weeks ]
  • Adherence as measured by questionnaire and visual analogue scale [ Time Frame: over 48 weeks ]
  • Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires [ Time Frame: over 48 weeks ]

Estimated Enrollment: 300
Study Start Date: June 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Active Comparator: SOC
triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI
Drug: SOC
Experimental: EVG +DRV/r
NRTI-sparing regimen - elvitegravir (EVG) + darunavir/ritonavir (DRV/r)
Drug: EVG +DRV/r


Ages Eligible for Study: 6 Years to 17 Years  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  


Inclusion Criteria:

  • HIV-1 infected children weighing ≥ 17 kg at the screening visit
  • Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
  • 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.
  • Children on a 3-drug PI/r or NNRTI containing regimen for at least 6 months.
  • Children/parents/guardians prepared to switch if randomised to elvitegravir + darunavir/ritonavir arm
  • Children and parents prepared to restart the current ART regimen after simplification if viral load restart criteria are met (see Section 5.5)
  • For children aged 6-12 either: 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 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:
  • Receiving or requiring agents with interactions with darunavir, RTV, or EVG
  • Evidence of resistance to DRV or integrase inhibitors (for participants in clinical sites where resistance testing is standard of care)
  • Previous exposure to integrase inhibitors for more than 2 weeks
  • History of previous encephalopathy
  • Intercurrent illness (randomisation can take place after the illness resolves)
  • Creatinine, AST or ALT of grade 3 or above at screening.
  • Diagnosis of tuberculosis and on anti-tuberculosis treatment (children can be enrolled after successful tuberculosis treatment)
  • Hepatitis B or Hepatitis C co-infection
  • Pregnancy or risk of pregnancy in girls of child-bearing potential unless committed to
taking effective contraception

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02383108


Contact:   Alexandra Compagnucci, MD +33(0)145595290


Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Pablo Rojo

Sponsors and Collaborators

PENTA Foundation
More Information

More Information

Responsible Party: PENTA Foundation Identifier: NCT02383108   History of Changes  
Other Study ID Numbers: SMILE (PENTA 17)  
Study First Received: February 19, 2015  
Last Updated: September 15, 2016  

Additional relevant MeSH terms:
HIV Infections
Darunavir processed this data on October 17, 2017
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