HIV InfectionPhase 2/3SMILENCT02383108
Strategy for Maintenance of HIV Suppression With Once Daily Integrate Inhibitor+Darunavir/Ritonavir in Children
A Phase 2/3 study testing DTG +DRV/r and SOC in people with HIV Infection, run by PENTA Foundation at 31 sites in 11 countries.
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. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- HIV Infection
- What is being tested?
- DTG +DRV/r and SOC
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 318 participants
- Where
- 31 sitesin 11 countries
- Study dates
- Jun 2016to Oct 2020
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
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- 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
Trial locations and contacts
31 sites in 11 countries.
31 sites in 11 countries
Spain6 sites
Hospital San Joan de Deu
Barcelona
Hospital Clínico San Carlos
Madrid
Hospital General Gregorio Marañón
Madrid
Hospital La Paz
Madrid
Hospital Universitario 12 de Octubre
Madrid
Hospital Universitario de Getafe
Madrid
Thailand6 sites
Prapokklao Hospital
Chanthaburi
Nakornping Hospital
Chiang Mai
Chiangrai Prachanukroh Hospital
Chiang Rai
Kalasin hospital
Kalasin
Khonkaen hospital
Khon Kaen
Phayao hospital
Phayao
United Kingdom4 sites
Birmingham Heartlands Hospital
Birmingham
Bristol Hospital
Bristol
Evelina Children Hospital, St Thomas's Hospital
London
King's College Hospital
London
Switzerland3 sites
Inselpital Bern
Bern
Kantonsspital St Gallen
Sankt Gallen
Kinderspital Zurich
Zurich
France2 sites
Centre Hospitalier Andrée Rosemon
Cannes
CHU Hôtel Dieu - Nantes
Nantes
Portugal2 sites
Hospital de Dona Estefânia - CHLC
Lisbon
Centro Materno-Infantil de Norte
Porto
About this study
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.
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.
Read the detailed description
A two arm parallel group, non-inferiority, open-label, multi-centre, randomised controlled trial.
- Conditions
- HIV Infection
- Being tested
- DTG +DRV/r, SOC
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DTG +DRV/rDrug
NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r)
SOCDrug
Standard of care (continuing triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI)
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care group (SOC) | Active comparator | triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI Receives: Drug: SOC |
| DTG+DRV/r | Experimental | NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r) Receives: Drug: DTG +DRV/r |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks)
Measured: at any time up to week 48
Secondary outcomes (17)
Percentage of patients with HIV-1 RNA < 50 c/mL
Measured: at week 48
Percentage of patients with HIV-1 RNA ≥ 50 c/mL
Measured: at week 24
Percentage of patients withHIV-1 RNA ≥ 400c/mL
Measured: 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
Measured: over 48 weeks
All grade 3 or 4 laboratory adverse events
Measured: over 48 weeks
Any adverse event at least possibly related to study drugs or leading to treatment modifications
Measured: over 48 weeks
Occurrence of new resistance mutations
Measured: over 48 weeks
Changes in CD4 (absolute and percentage)
Measured: from baseline to weeks 24 and 48
Change in ART (defined as any change from the ART regimen at randomisation)
Measured: at week 0
New or recurrent CDC/WHO stage C or severe stage B event or death
Measured: over 48 weeks
Blood lipids
Measured: over 48 weeks
Adherence as measured by questionnaire and visual analogue scale
Measured: over 48 weeks
Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
Measured: over 48 weeks
Tanner scales (in participants aged over 8 years)
Measured: over 48 weeks
Date of first menses
Measured: over 48 weeks
Height
Measured: Over 48 weeks
Weight
Measured: over 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2015 (estimated)
- Study startJun 2016
- Primary completionAug 2020
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 318 participants (actual)
Sponsor and investigators
- Lead sponsor
- PENTA Foundation
- Sponsor type
- Research network
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, University College, London, PHPT
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02383108
- Sponsor's protocol ID
- SMILE (PENTA 17)
- Other IDs
- ANRS1 52
- Acronym
- SMILE
- Status last verified
- Mar 2021
- First submitted
- 19 Feb 2015
- Last updated
- 30 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37304494
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02383108
- Acronym / sponsor ID
- SMILE / SMILE (PENTA 17)
- Conditions
- HIV Infection
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 318 participants (actual)
- Lead sponsor
- PENTA FoundationResearch network
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, University College, London, PHPT
- Study start
- Jun 2016
- Primary completion
- Aug 2020 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 9 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
A two arm parallel group, non-inferiority, open-label, multi-centre, randomised controlled trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard of Care group (SOC) | Active comparator | Drug: SOCtriple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI |
| DTG+DRV/r | Experimental | Drug: DTG +DRV/rNRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r) |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DTG +DRV/rNRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r) | Drug | DTG+DRV/r |
| SOCStandard of care (continuing triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI) | Drug | Standard of Care group (SOC) |
Primary outcome
Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks)
Time frame: at any time up to week 48
17 secondary outcomes
Percentage of patients with HIV-1 RNA < 50 c/mL
Time frame: at week 48
Percentage of patients with HIV-1 RNA ≥ 50 c/mL
Time frame: at week 24
Percentage of patients withHIV-1 RNA ≥ 400c/mL
Time frame: 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
Time frame: over 48 weeks
All grade 3 or 4 laboratory adverse events
Time frame: over 48 weeks
Any adverse event at least possibly related to study drugs or leading to treatment modifications
Time frame: over 48 weeks
Occurrence of new resistance mutations
Time frame: over 48 weeks
Changes in CD4 (absolute and percentage)
Time frame: from baseline to weeks 24 and 48
Change in ART (defined as any change from the ART regimen at randomisation)
Time frame: at week 0
New or recurrent CDC/WHO stage C or severe stage B event or death
Time frame: over 48 weeks
Blood lipids
Time frame: over 48 weeks
Adherence as measured by questionnaire and visual analogue scale
Time frame: over 48 weeks
Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
Time frame: over 48 weeks
Tanner scales (in participants aged over 8 years)
Time frame: over 48 weeks
Date of first menses
Time frame: over 48 weeks
Height
Time frame: Over 48 weeks
Weight
Time frame: over 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2021.
- Derived from this study: PubMed 37304494Compagnucci 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
31 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing DTG +DRV/r and SOC in people with HIV Infection, run by PENTA Foundation at 31 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in Spain, Thailand, United Kingdom, Switzerland, France and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks) (time frame: at any time up to week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02383108, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2021.