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

PENTA Foundation

Status and phase: Completed; Phase 3; Phase 2

Conditions: HIV Infection

Treatments: Drug: DTG +DRV/r; Drug: SOC

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT02383108

SMILE (PENTA 17)

ANRS1 52 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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

Enrollment: 318 patients

Sex: All

Ages: 12 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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318 participants in 2 patient groups

Standard of Care group (SOC)

Active Comparator group

Description:

triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI

Treatment:

Drug: SOC

DTG+DRV/r

Experimental group

Description:

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

Treatment:

Drug: DTG +DRV/r