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

NCT02383108 | Completed Phase 2 DMC

• 2 other identifiers: SMILE (PENTA 17)ANRS1 52
• Study Type: interventional
• Target: 318
• Locations: 11 countries
• Sites: 31

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.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks)

  at any time up to week 48

Secondary Outcomes (17)

• Percentage of patients with HIV-1 RNA < 50 c/mL

  at week 48

• Percentage of patients with HIV-1 RNA ≥ 50 c/mL

  at week 24

• Percentage of patients withHIV-1 RNA ≥ 400c/mL

  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

  over 48 weeks

• All grade 3 or 4 laboratory adverse events

  over 48 weeks

Study Arms (2)

Standard of Care group (SOC)

ACTIVE COMPARATOR

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

Drug: SOC

DTG+DRV/r

EXPERIMENTAL

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

Drug: DTG +DRV/r

Interventions

DTG +DRV/r DRUG

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

DTG+DRV/r

SOC DRUG

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

Standard of Care group (SOC)

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• HIV-1 infected children aged ≥ 12 years old and weighing ≥40kg\* at the screening visit
• Aged 12 to \< 18 years old\*\*
• Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol
• 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.
• Children on a 3-drug PI/r or NNRTI containing regimen for at least 24 weeks
• Children/parents/guardians prepared to switch if randomised to once daily integrase inhibitor + DRV/RTV arm
• Children and parents prepared to restart the current ART regimen after simplification if viral load restart criteria are met (see Section 5.5)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (31)

Hospital Garrahan

Buenos Aires, Argentina

Location

Centre Hospitalier Andrée Rosemon

Cannes, France

Location

CHU Hôtel Dieu - Nantes

Nantes, France

Location

Hospital General Mexico

Mexico City, Mexico

Location

Hospital de Dona Estefânia - CHLC

Lisbon, Portugal

Location

Centro Materno-Infantil de Norte

Porto, Portugal

Location

FAM-CRU

Cape Town, South Africa

Location

PHRU

Soweto, South Africa

Location

Hospital San Joan de Deu

Barcelona, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital General Gregorio Marañón

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario de Getafe

Madrid, Spain

Location

Inselpital Bern

Bern, Switzerland

Location

Kantonsspital St Gallen

Sankt Gallen, Switzerland

Location

Kinderspital Zurich

Zurich, Switzerland

Location

Prapokklao Hospital

Chanthaburi, Thailand

Location

Nakornping Hospital

Chiang Mai, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiang Rai, Thailand

Location

Kalasin hospital

Kalasin, Thailand

Location

Khonkaen hospital

Khon Kaen, Thailand

Location

Phayao hospital

Phayao, Thailand

Location

Baylor

Kampala, Uganda

Location

JCRC

Mbarara, Uganda

Location

Kiev

Kiev, Ukraine

Location

Kryvyi Rih

Kryvyi Rih, Ukraine

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Bristol Hospital

Bristol, United Kingdom

Location

Evelina Children Hospital, St Thomas's Hospital

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

Related Publications (1)

• Compagnucci A, Chan MK, Saidi Y, Cressey TR, Bamford A, Riault Y, Coelho A, Nolan A, Chalermpantmetagul S, Morkunaite G, Amuge P, Musiime V, Violari A, Cotton M, Kekitiinwa AR, Kaudha E, Groenewald M, Liberty AA, Kanjanavanit S, Volokha A, Bologna R, Pavia Ruz N, Prieto Tato L, Paioni P, Marques L, Reliquet V, Niehues T, Welch SB, Ford D, Giaquinto C, Gibb DM, Babiker A, Ramos Amador JT; SMILE-PENTA17-ANRS 152 Trial Group. Nucleoside/nucleotide reverse transcriptase inhibitor sparing regimen with once daily integrase inhibitor plus boosted darunavir is non-inferior to standard of care in virologically-suppressed children and adolescents living with HIV - Week 48 results of the randomised SMILE Penta-17-ANRS 152 clinical trial. EClinicalMedicine. 2023 Jun 2;60:102025. doi: 10.1016/j.eclinm.2023.102025. eCollection 2023 Jun.

  PMID: 37304494 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: March 9, 2015
• Study Start: June 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: October 1, 2020
• Last Updated: March 30, 2021

Record last verified: 2021-03

Locations

TH (6); AR (1); ME (1); PT (2); GB (4); ZA (2); UG (2); ES (6); FR (2); UA (2); CH (3)