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

Sponsor
PENTA Foundation (Other)
Overall Status
Completed
CT.gov ID
NCT02383108
Collaborator
Institut National de la Santé Et de la Recherche Médicale, France (Other), MRC CTU at UCL (Other), PHPT (Other)
318
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2
52
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Study Details

Study Description

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
Phase 2/Phase 3

Detailed Description

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

Study Design

Study Type:
Interventional
Actual Enrollment :
318 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 :
Jun 1, 2016
Actual Primary Completion Date :
Aug 1, 2020
Actual Study Completion Date :
Oct 1, 2020

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

  1. Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks) [at any time up to week 48]

Secondary Outcome Measures

  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. Percentage of patients with any grade 3 or 4 clinical adverse events (particularly lipodystrophy); any grade 3 or 4 laboratory adverse events [over 48 weeks]

  5. All grade 3 or 4 laboratory adverse events [over 48 weeks]

  6. Any adverse event at least possibly related to study drugs or leading to treatment modifications [over 48 weeks]

  7. Occurrence of new resistance mutations [over 48 weeks]

  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) [at week 0]

  10. New or recurrent CDC/WHO stage C or severe stage B event or death [over 48 weeks]

  11. Blood lipids [over 48 weeks]

  12. Adherence as measured by questionnaire and visual analogue scale [over 48 weeks]

  13. Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires [over 48 weeks]

  14. Tanner scales (in participants aged over 8 years) [over 48 weeks]

  15. Date of first menses [over 48 weeks]

  16. Height [Over 48 weeks]

  17. Weight [over 48 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 17 Years
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 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hospital Garrahan Buenos Aires Argentina
2 Centre Hospitalier Andrée Rosemon Cannes France
3 CHU Hôtel Dieu - Nantes Nantes France
4 Hospital General Mexico Mexico City Mexico
5 Hospital de Dona Estefânia - CHLC Lisbon Portugal
6 Centro Materno-Infantil de Norte Porto Portugal
7 FAM-CRU Cape Town South Africa
8 PHRU Soweto South Africa
9 Hospital San Joan de Deu Barcelona Spain
10 Hospital Clínico San Carlos Madrid Spain
11 Hospital General Gregorio Marañón Madrid Spain
12 Hospital La Paz Madrid Spain
13 Hospital Universitario 12 de Octubre Madrid Spain
14 Hospital Universitario de Getafe Madrid Spain
15 Inselpital Bern Bern Switzerland
16 Kantonsspital St Gallen Saint Gallen Switzerland
17 Kinderspital Zurich Zürich Switzerland
18 Prapokklao Hospital Chanthaburi Thailand
19 Nakornping Hospital Chiang Mai Thailand
20 Chiangrai Prachanukroh Hospital Chiang Rai Thailand
21 Kalasin hospital Kalasin Thailand
22 Khonkaen hospital Khon Kaen Thailand
23 Phayao hospital Phayao Thailand
24 Baylor Kampala Uganda
25 JCRC Mbarara Uganda
26 Kiev Kiev Ukraine
27 Kryvyi Rih Kryvyi Rih Ukraine
28 Birmingham Heartlands Hospital Birmingham United Kingdom
29 Bristol Hospital Bristol United Kingdom
30 Evelina Children Hospital, St Thomas's Hospital London United Kingdom
31 King's College Hospital London United Kingdom

Sponsors and Collaborators

  • PENTA Foundation
  • Institut National de la Santé Et de la Recherche Médicale, France
  • MRC CTU at UCL
  • PHPT

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
PENTA Foundation
ClinicalTrials.gov Identifier:
NCT02383108
Other Study ID Numbers:
  • SMILE (PENTA 17)
  • ANRS1 52
First Posted:
Mar 9, 2015
Last Update Posted:
Mar 30, 2021
Last Verified:
Mar 1, 2021
Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 30, 2021