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

March 25, 2021 updated by: PENTA Foundation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
318

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

12 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard of Care group (SOC)
triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI
Drug: SOC
Standard of care (continuing triple anti-retroviral therapy including 2 NRTIs + boosted PI/NNRTI)
Experimental: DTG+DRV/r
NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r)
Drug: DTG +DRV/r
NRTI-sparing regimen: Once daily integrase inhibitor (INSTI) + darunavir/ritonavir (DRV/r)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Percentage of patients with HIV-1 RNA ever ≥ 50 c/mL (confirmed within 4 weeks)
Time Frame: at any time up to week 48
at any time up to week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentage of patients with HIV-1 RNA < 50 c/mL
Time Frame: at week 48
at week 48
Percentage of patients with HIV-1 RNA ≥ 50 c/mL
Time Frame: at week 24
at week 24
Percentage of patients withHIV-1 RNA ≥ 400c/mL
Time Frame: at week 24 and week 48
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
over 48 weeks
All grade 3 or 4 laboratory adverse events
Time Frame: over 48 weeks
over 48 weeks
Any adverse event at least possibly related to study drugs or leading to treatment modifications
Time Frame: over 48 weeks
over 48 weeks
Occurrence of new resistance mutations
Time Frame: over 48 weeks
over 48 weeks
Changes in CD4 (absolute and percentage)
Time Frame: from baseline to weeks 24 and 48
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
at week 0
New or recurrent CDC/WHO stage C or severe stage B event or death
Time Frame: over 48 weeks
over 48 weeks
Blood lipids
Time Frame: over 48 weeks
over 48 weeks
Adherence as measured by questionnaire and visual analogue scale
Time Frame: over 48 weeks
over 48 weeks
Acceptability and quality of life over 48 weeks as assessed by patient completed questionnaires
Time Frame: over 48 weeks
over 48 weeks
Tanner scales (in participants aged over 8 years)
Time Frame: over 48 weeks
over 48 weeks
Date of first menses
Time Frame: over 48 weeks
over 48 weeks
Height
Time Frame: Over 48 weeks
Over 48 weeks
Weight
Time Frame: over 48 weeks
over 48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PENTA Foundation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Institut National de la Santé Et de la Recherche Médicale, France
MRC CTU at UCL
PHPT

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 19, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 3, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 9, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SMILE (PENTA 17)
  • ANRS1 52 (Other Identifier: France Agency for research on AIDS and viral hepatitis)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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