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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02383108
Recruitment Status : Recruiting
First Posted : March 9, 2015
Last Update Posted : November 17, 2017
Information provided by (Responsible Party):
PENTA Foundation

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.

Condition or disease Intervention/treatment Phase
HIV Infection Drug: DTG +DRV/r Drug: SOC Phase 2 Phase 3

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
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.
Study Start Date : June 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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)

Primary Outcome Measures :
  1. 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 :
  1. Percentage of patients with HIV-1 RNA < 50 c/mL [ Time Frame: at week 48 ]
  2. Percentage of patients with HIV-1 RNA ≥ 50 c/mL [ Time Frame: at week 24 ]
  3. Percentage of patients withHIV-1 RNA ≥ 400c/mL [ Time Frame: at week 24 and week 48 ]
  4. 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 ]
  5. All grade 3 or 4 laboratory adverse events [ Time Frame: over 48 weeks ]
  6. Any adverse event at least possibly related to study drugs or leading to treatment modifications [ Time Frame: over 48 weeks ]
  7. Occurrence of new resistance mutations [ Time Frame: over 48 weeks ]
  8. Changes in CD4 (absolute and percentage) [ Time Frame: from baseline to weeks 24 and 48 ]
  9. Change in ART (defined as any change from the ART regimen at randomisation) [ Time Frame: at week 0 ]
  10. New or recurrent CDC/WHO stage C or severe stage B event or death [ Time Frame: over 48 weeks ]
  11. Blood lipids [ Time Frame: over 48 weeks ]
  12. Adherence as measured by questionnaire and visual analogue scale [ Time Frame: over 48 weeks ]
  13. Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires [ Time Frame: over 48 weeks ]
  14. Tanner scales (in participants aged over 8 years) [ Time Frame: over 48 weeks ]
  15. Date of first menses [ Time Frame: over 48 weeks ]
  16. Height [ Time Frame: Over 48 weeks ]
  17. Weight [ Time Frame: over 48 weeks ]

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

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:

  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02383108

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

Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: Pablo Rojo   
Sponsors and Collaborators
PENTA Foundation

Responsible Party: PENTA Foundation Identifier: NCT02383108     History of Changes
Other Study ID Numbers: SMILE (PENTA 17)
First Posted: March 9, 2015    Key Record Dates
Last Update Posted: November 17, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
HIV Infections
Anti-HIV Agents
Anti-Retroviral Agents
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Integrase Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors