Clinical Trials

MainTitle

Strategy for Maintenance of HIV Suppression With Once Daily Integrate Inhibitor+Darunavir/Ritonavir in Children (SMILE)

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

Verified November 2017 by PENTA Foundation

Sponsor
PENTA Foundation


Information provided by (Responsible Party)
PENTA Foundation
ClinicalTrials.gov Identifier
NCT02383108

First received: February 19, 2015
Last updated: November 14, 2017
Last Verified: November 2017
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV Infection

Drug : DTG +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 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.

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 ]
  • Percentage of patients with any grade 3 or 4 clinical adverse events (particularly lipodystrophy); any grade 3 or 4 laboratory adverse events [ 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 ]
  • Tanner scales (in participants aged over 8 years) [ Time Frame: over 48 weeks ]
  • Date of first menses [ Time Frame: over 48 weeks ]
  • Height [ Time Frame: Over 48 weeks ]
  • Weight [ 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: Standard of Care group (SOC)
triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI
Drug: SOC

Standard of care (continuing triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI)

Experimental: DTG+DRV/r
NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r)
Drug: DTG +DRV/r

NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r)

Detailed Description:

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

Eligibility

Eligibility

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

Criteria

Inclusion Criteria:

  1. HIV-1 infected children aged ≥ 12 years old and weighing ≥40kg* 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 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:
  • Receiving or requiring agents with interactions with DRV, RTV, or any once daily integrase inhibitor (Appendix 14)
  • 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
  • Intercurrent illness (randomisation can take place after the illness resolves)
  • Creatinine ≥ 1.8ULN or ALT ≥ 5ULN or ALT ≥ 3ULN and bilirubin ≥2ULN at screening.
  • 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)
  • 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
  • History or presence of known allergy or some other contraindication to the study drugs or their components as described in the SmPC

    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 ClinicalTrials.gov identifier: NCT02383108

    Contacts

    Contact:   Alexandra Compagnucci, MD +33(0)145595290 alexandra.compagnucci@inserm.fr

    Locations

    Spain
    Hospital Universitario 12 de Octubre Recruiting
    Madrid, Spain
    Contact: Pablo Rojo    pablorojoconejo@netscape.net

    Sponsors and Collaborators

    PENTA Foundation
    More Information

    More Information


    Responsible Party: PENTA Foundation  
    ClinicalTrials.gov Identifier: NCT02383108   History of Changes  
    Other Study ID Numbers: SMILE (PENTA 17)  
    Study First Received: February 19, 2015  
    Last Updated: November 14, 2017  

    Additional relevant MeSH terms:
    HIV Infections
    Ritonavir
    Darunavir
    Integrase Inhibitors

    ClinicalTrials.gov processed this data on December 15, 2017
    This information is provided by ClinicalTrials.gov.