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

NCT ID: NCT02383108

Last Updated: 2021-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

318 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-30

Study Completion Date

2020-10-31

Brief Summary

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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.

Detailed Description

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

Conditions

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HIV Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard of Care group (SOC)

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

Group Type ACTIVE_COMPARATOR

SOC

Intervention Type DRUG

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

DTG+DRV/r

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

Group Type EXPERIMENTAL

DTG +DRV/r

Intervention Type DRUG

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

Interventions

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DTG +DRV/r

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

Intervention Type DRUG

SOC

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

12 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

MRC CTU at UCL

UNKNOWN

Sponsor Role collaborator

PHPT

UNKNOWN

Sponsor Role collaborator

PENTA Foundation

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Garrahan

Buenos Aires, , Argentina

Site Status

Centre Hospitalier Andrée Rosemon

Cannes, , France

Site Status

CHU Hôtel Dieu - Nantes

Nantes, , France

Site Status

Hospital General Mexico

Mexico City, , Mexico

Site Status

Hospital de Dona Estefânia - CHLC

Lisbon, , Portugal

Site Status

Centro Materno-Infantil de Norte

Porto, , Portugal

Site Status

FAM-CRU

Cape Town, , South Africa

Site Status

PHRU

Soweto, , South Africa

Site Status

Hospital San Joan de Deu

Barcelona, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital General Gregorio Marañón

Madrid, , Spain

Site Status

Hospital La Paz

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario de Getafe

Madrid, , Spain

Site Status

Inselpital Bern

Bern, , Switzerland

Site Status

Kantonsspital St Gallen

Sankt Gallen, , Switzerland

Site Status

Kinderspital Zurich

Zurich, , Switzerland

Site Status

Prapokklao Hospital

Chanthaburi, , Thailand

Site Status

Nakornping Hospital

Chiang Mai, , Thailand

Site Status

Chiangrai Prachanukroh Hospital

Chiang Rai, , Thailand

Site Status

Kalasin hospital

Kalasin, , Thailand

Site Status

Khonkaen hospital

Khon Kaen, , Thailand

Site Status

Phayao hospital

Phayao, , Thailand

Site Status

Baylor

Kampala, , Uganda

Site Status

JCRC

Mbarara, , Uganda

Site Status

Kiev

Kiev, , Ukraine

Site Status

Kryvyi Rih

Kryvyi Rih, , Ukraine

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

Bristol Hospital

Bristol, , United Kingdom

Site Status

Evelina Children Hospital, St Thomas's Hospital

London, , United Kingdom

Site Status

King's College Hospital

London, , United Kingdom

Site Status

Countries

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

References

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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.

Reference Type DERIVED
PMID: 37304494 (View on PubMed)

Other Identifiers

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ANRS1 52

Identifier Type: OTHER

Identifier Source: secondary_id

SMILE (PENTA 17)

Identifier Type: -

Identifier Source: org_study_id

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