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

HIV Infection Clinical Trial

— SMILE  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02383108
• Other study ID #: SMILE (PENTA 17)
• Secondary ID: ANRS1 52
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 2016
• Est. completion date: October 2020

Study information

• Verified date: March 2021
• Source: PENTA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: October 2020
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Drug:
• DTG +DRV/r
NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r)
• SOC
Standard of care (continuing triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI)

Locations

Country	Name	City	State
Argentina	Hospital Garrahan	Buenos Aires
France	Centre Hospitalier Andrée Rosemon	Cannes
France	CHU Hôtel Dieu - Nantes	Nantes
Mexico	Hospital General Mexico	Mexico City
Portugal	Hospital de Dona Estefânia - CHLC	Lisbon
Portugal	Centro Materno-Infantil de Norte	Porto
South Africa	FAM-CRU	Cape Town
South Africa	PHRU	Soweto
Spain	Hospital San Joan de Deu	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Gregorio Marañón	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de Getafe	Madrid
Switzerland	Inselpital Bern	Bern
Switzerland	Kantonsspital St Gallen	Saint Gallen
Switzerland	Kinderspital Zurich	Zürich
Thailand	Prapokklao Hospital	Chanthaburi
Thailand	Nakornping Hospital	Chiang Mai
Thailand	Chiangrai Prachanukroh Hospital	Chiang Rai
Thailand	Kalasin hospital	Kalasin
Thailand	Khonkaen hospital	Khon Kaen
Thailand	Phayao hospital	Phayao
Uganda	Baylor	Kampala
Uganda	JCRC	Mbarara
Ukraine	Kiev	Kiev
Ukraine	Kryvyi Rih	Kryvyi Rih
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Bristol Hospital	Bristol
United Kingdom	Evelina Children Hospital, St Thomas's Hospital	London
United Kingdom	King's College Hospital	London

Sponsors (4)

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

Countries where clinical trial is conducted

Argentina,  France,  Mexico,  Portugal,  South Africa,  Spain,  Switzerland,  Thailand,  Uganda,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with HIV-1 RNA ever = 50 c/mL (confirmed within 4 weeks)		at any time up to week 48
Secondary	Percentage of patients with HIV-1 RNA < 50 c/mL		at week 48
Secondary	Percentage of patients with HIV-1 RNA = 50 c/mL		at week 24
Secondary	Percentage of patients withHIV-1 RNA = 400c/mL		at week 24 and week 48
Secondary	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
Secondary	All grade 3 or 4 laboratory adverse events		over 48 weeks
Secondary	Any adverse event at least possibly related to study drugs or leading to treatment modifications		over 48 weeks
Secondary	Occurrence of new resistance mutations		over 48 weeks
Secondary	Changes in CD4 (absolute and percentage)		from baseline to weeks 24 and 48
Secondary	Change in ART (defined as any change from the ART regimen at randomisation)		at week 0
Secondary	New or recurrent CDC/WHO stage C or severe stage B event or death		over 48 weeks
Secondary	Blood lipids		over 48 weeks
Secondary	Adherence as measured by questionnaire and visual analogue scale		over 48 weeks
Secondary	Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires		over 48 weeks
Secondary	Tanner scales (in participants aged over 8 years)		over 48 weeks
Secondary	Date of first menses		over 48 weeks
Secondary	Height		Over 48 weeks
Secondary	Weight		over 48 weeks