Clinical Trials

MainTitle

The Late Presenter Treatment Optimisation Study (LAPTOP)

This study is currently recruiting participants. (see Contacts and Locations)

Verified August 2019 by NEAT ID Foundation

Sponsor
NEAT ID Foundation

Collaborator
Gilead Sciences
Janssen Pharmaceuticals

Information provided by (Responsible Party)
NEAT ID Foundation
ClinicalTrials.gov Identifier
NCT03696160

First received: September 24, 2018
Last updated: August 27, 2019
Last Verified: August 2019
History of Changes
Purpose

Purpose

The main purpose of this study is to compare two different types of HIV treatments, in terms of effectiveness and improvement of side effects, for patients who are diagnosed with a more advanced HIV infection. Patients with advanced HIV infections are otherwise known as 'late presenters'.

There are many effective treatments for HIV available; however, for late presenting patients the investigators do not know which type of treatment performs best. This is the first large study to compare treatments for patients in this situation, and the investigators hope that the results of this study will help doctors decide which treatments to use in the future.

The two different types of treatment the investigators are comparing both contain a mixture of drugs that work together to combat HIV:

The Boosted Protease Inhibitor combination (PI) which is a combination tablet containing: darunavir, cobicistat, emtricitabine and tenofovir alafenamide. It was approved for use in Europe under the brand name Symtuza®.

The Integrase Inhibitor combination (INI). Which is a combination tablet containing: bictegravir, emtricitabine and tenofovir alafenamide. This is a a newer combination which was approved for use in Europe in June 2018 under the brand name of Biktarvy®.

The main difference between the two treatments is how each one fights a HIV infection. They both stop a part of the virus from working (i.e. inhibit it), to prevent it from making copies of itself. The PI treatment contains drugs to stop the protease part of the virus, whereas the INI treatment contains drugs to stop the integrase part.

In recent studies, it appears that treatments containing integrase inhibitors may be better for late presenting patients. They have been shown to quickly bring down the amount of virus in the body, and the side effects may be more acceptable to late presenters.

To compare the two treatments, half of the participants on this study will be given the PI treatment, and the other half will be given the INI treatment.

Condition Intervention Phase
HIV/AIDS

Drug : Biktarvy
Drug : Symtuza
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multi-Centre, Randomised Study to Investigate Integrase Inhibitor Versus Boosted Protease Inhibitor Antiretroviral Therapy for Patients With Advanced HIV Disease

Further study details as provided by NEAT ID Foundation:

Primary Outcome Measures

  • Time to treatment failure [ Time Frame: Earliest at 12 weeks, latest 48 weeks ]
    Composite outcome: time to treatment failure due to either virological or clinical reasons. Virological reasons can either be insufficient virological response or viral rebound. Clinical reasons can be death related to HIV/AIDS/opportunistic infection or severe bacterial infection, new or recurrent AIDS defining event, any serious non-AIDS defining event or clinically relevant adverse events of any grade or immune reconstitution inflammatory syndrome requiring treatment
Secondary Outcome Measures:
  • Proportion of patients with HIV-RNA viral load <50 copies/mL [ Time Frame: Week 24, 36 and 48 ]
  • HIV-1 drug resistance confirmed [ Time Frame: Through study completion, an average of 1 year ]
  • Time to reach CD4 (cluster of differentiation 4) count >200/µL [ Time Frame: Through study completion, an average of 1 year ]
  • CD4/CD8 (cluster of differentiation 8) ratio [ Time Frame: Week 4, 8, 12, 24, 36, 48 ]
  • Incidence of Immune Reconstitution Inflammatory Syndrome [ Time Frame: Week 48 ]
  • Incidence and duration of hospitalisation or rate of relapse of specific opportunistic or bacterial infection [ Time Frame: Week 48 ]
    Start/Stop of hospitalization for any reason Start/Stop of opportunistic infections as listed within Appendix 3 (AIDS defining events according to https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a2.htm) Start/Stop of severe BI, which consists of any of bacterial pneumonia, invasive bacterial infection (IBI) or any bacterial infectious disorder with grade 3 severity or requiring unscheduled hospital admission. An IBI is defined as the isolation of a bacterial organism from a normally sterile body site, or for bacterial nucleic acid to be detected at a normally sterile body site. Sterile body sites include blood, cerebrospinal fluid, pleural fluid, pericardial fluid, peritoneal fluid, joint fluid, bone aspirate, or a deep tissue abscess.
  • Number of participants with treatment-related adverse events as assessed by Division of AIDS Adverse Event (AE) Grading Table Corrected Version 2.1-July 2017 [ Time Frame: Week 48 ]
  • Antiretroviral therapy and opportunistic or bacterial infection treatment changes and dose modifications due to toxicities and drug-drug interaction with antiretroviral therapy, and Immune Reconstitution Inflammatory Syndrome [ Time Frame: Week 48 ]
  • Health care resource use, including total inpatient days and emergency room visits [ Time Frame: Week 48 ]
  • Quality of life questionnaire outcomes [ Time Frame: Week 48 ]
    EQ-5D-3L (European Quality of life - 5 Dimensions - 3 Levels) questionnaires will be completed by patients throughout the study to assess any change throughout their treatment
  • Discontinuation or modification of study medication due to insufficient virological response or resistance mutation development [ Time Frame: Week 48 ]
    Discontinuation or modification of the single tablet regimen due virological reasons defined as a) Insufficient virological response, either: HIV-1 RNA reduction < 1 log 10 copies/mL at week 12, or Viral load > 50 HIV-1 RNA copies/mL at week 48 b) Viral rebound, which is subsequently confirmed at the following scheduled or unscheduled visit, defined as either: a. Rebound of HIV-1 RNA to >200 copies/mL after having achieved HIV-1 RNA <50 copies/mL b. Rebound of HIV RNA by >1 log 10 copies/mL from nadir value, for patients whose viral load has never been suppressed below 50 copies/mL
Other Outcome Measures:
  • Mutations detected by deep sequencing compared with those detected by population sequencing [ Time Frame: Week 48 ]
    The resistance associated mutations in genes encoding the reverse transcriptase, protease and integrase of HIV as detected by ultra-deep sequencing and sanger sequencing.
  • Proportion of patients with HIV-RNA viral load < 50 copies/mL [ Time Frame: Week 4, 8, 12 ]

Estimated Enrollment: 440
Study Start Date: March 5, 2019
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Biktarvy
Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food.
Drug: Biktarvy

Integrase inhibitor used to treat HIV-1 infection

Experimental: Symtuza
Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food.
Drug: Symtuza

Protease inhibitor used to treat HIV-1 infection

Detailed Description:

The effectiveness of HIV antiretroviral therapy (ART) has consistently improved over the years. This is largely due to newer drugs having improved antiviral effectiveness and more tolerable side effect profiles; resulting in better viral suppression and improved treatment adherence. On the other hand, most recent clinical trials look at the effectiveness of ART in patients with less advanced disease. These patients usually suffer from less related diseases, drug-drug interactions, and other risks for treatment failure. Outside of these trials, the number of patients who present to clinic with a more developed advanced HIV infection, known as 'late presenters', remains high across Europe. Trials for these patients have tended to focus on the time of starting treatment and the management of infections.
Much less is known about which ART treatments perform best for these late presenting patients; particularly in terms of virus suppression, immune system recovery, side effects and improvement of AIDs related diseases. No specific drug combinations have been compared in appropriate clinical trials before, and the international guidelines for first line treatment judge all therapies as equal standard of care for these patients.
The investigators anticipate that Integrase inhibitor containing regimes may be better suited to patients with advanced disease, due to their beneficial side-effect profile and ability to rapidly decrease viral load levels. Therefore the investigators are conducting this clinical trial to compare an integrase inhibitor regime, against a protease inhibitor regime in patients with advanced HIV infection. The aim of the study is to demonstrate the non-inferiority of Biktarvy® against Symtuza®.
Patients will be recruited from sites across Europe, and randomized onto either arm of the study. After randomisation onto either treatment regime, patients will attend approximately 9 follow-up visits over the course of a year. During these visits, patients will be asked to complete two questionnaires, to assess their quality of life and HIV symptoms. They will also be asked to provide a number of blood samples. These samples are to ensure that the patient is not resistant to the study drug and that their disease is not worsening. Samples to test for study drug resistance will be shipped to a laboratory for analysis in the even that the patient experiences virological failure.
Biktarvy® will be supplied from Gilead and Symtuza® will be provided by Janssen Pharmaceuticals.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria:

    1. The ability to understand and sign a written informed consent form (ICF) and must be willing to comply with all study requirements.
    2. Male or non-pregnant, non-lactating females.
    3. Age ≥ 18 years.
    4. Has documented, untreated HIV-1 infection with either:
        1. AIDS with any CD4 cell count (AIDS-defining conditions are listed within Appendix 3).

        Or
      1. Severe bacterial infection (BI) and must have a CD4 cell count < 200/µl within 30 days prior to study entry.

      Or
    5. Are asymptomatic with CD4 cell count < 100/µL within 30 days prior to study entry and must have an entry HIV viral load > 1000 copies/mL.

    Or
  1. Currently receiving treatment for opportunistic infection (OI) i. Subjects with other serious OIs, including other AIDS-defining and AIDS-related OIs for which appropriate therapy other than ART exists are eligible, but Investigator approval must be obtained.

ii. Current OI treatment must have been started ≤ 14 days prior to study entry, but can have been discontinued prior to study entry.
  • Have the ability to take oral medications.
  • If female and of childbearing potential, is using effective birth control methods (see Appendix 7) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the last dose of study medication. Note:
      Non-childbearing potential is defined as either post-menopausal (12 months of spontaneous amenorrhoea and ≥45 years) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy.
    1. If a heterosexually active male, is using effective birth control methods and is willing to continue practising these birth control methods during the trial and for at least 30 days after the last dose of study medication.


    Exclusion Criteria:
      1. Any antiretroviral prior to study entry.
      2. Systemic cancer chemotherapy within 30 days prior to study entry, or current treatment for cancer (with the exception of Kaposi's sarcoma) or lymphoma.
      3. Current or anticipated use of contraindicated medications (see Summary of Product Characteristics (SmPC) for Symtuza® and Investigator's Brochure (IB) for Biktarvy®) or anticipated systemic chemotherapy during study enrolment (administration of any contraindicated medication must be discontinued at least 30 days prior to the baseline visit and for the duration of the study).
      4. Known resistance to the components of study medications (see section 6.1.3 for more details).
      5. History or symptoms of advanced renal and/or hepatic impairment. Such as, kidney failure requiring dialysis; eGFR (epidermal growth factor receptor) <30 mL/min; hepatic transaminases (AST and ALT) > 5 x upper limit of normal (ULN); or, platelet count <50,000.
      6. Current drug or alcohol use that, in the opinion of the Investigator, would cause interference with the study.
      7. Cryptococcal meningitis or active tuberculosis (TB) or current or expected treatment requiring Rifampicin or Rifabutin (patients with expected latent TB will have a TB test (IGRAs e.g. ELISPOT, QuantiFERON etc.) at their screening visit).
      8. History or presence of allergy to the study drugs or their components, or drugs of their class.
      9. Using any concomitant therapy disallowed as per the reference safety information (RSI) and product labelling for the study drugs.
      10. Any investigational drug within 30 days prior to the study drug administration.
      11. Patients with severe (Child Pugh class C) hepatic impairment.
      12. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
      13. Females of childbearing potential and heterosexually active males must be willing to
      use a highly effective method of contraception. See Appendix 7 for further details. Such methods include:

    a. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

  • i. oral
    ii.intravaginal
    iii.transdermal
    b.progestogen-only hormonal contraception associated with inhibition of ovulation
    i.oral
    ii. injectable
    iii.implantable
    c. intrauterine device (IUD)
    d. intrauterine hormone-releasing system (IUS)
    e. bilateral tubal occlusion
    f. vasectomised partner
    g. sexual abstinence (with male partners)

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT03696160

    Contacts

    Contact:   LAPTOP Project Manager +44 203 859 7747 laptop@rokcservices.com
    Contact:   LAPTOP Project Manager +44 203 859 7747 laptop@neat-id.com

    Locations

    Belgium
    Institute of Tropical Medicine Not yet recruiting
    Antwerp, Belgium
    Contact: Eric Florence
    Principal Investigator: Eric Florence
    CHU Saint-Pierre Not yet recruiting
    Brussels, Belgium
    Contact: Stephane De Wit
    Principal Investigator: Stephane De Wit
    University Hospital Ghent Not yet recruiting
    Gent, Belgium
    Contact: Linos Vandekerckhove
    Principal Investigator: Linos Vandekerckhove
    France
    Hôpital Gui de Chauliac Not yet recruiting
    Montpellier, France
    Contact: Jacques Reynes
    Principal Investigator: Jacques Reynes
    CHU de Nantes Not yet recruiting
    Nantes, France
    Contact: Francois Raffi
    Principal Investigator: Francois Raffi
    Hopital Saint-Louis Not yet recruiting
    Paris, France
    Contact: Jean-Michael Molina
    Principal Investigator: Jean-Michael Molina
    Hôpital Saint Antoine Not yet recruiting
    Paris, France
    Contact: Karine Lacombe
    Principal Investigator: Karine Lacombe
    Pitié-Salpêtrière Hospital Not yet recruiting
    Paris, France
    Contact: Christine Katlama
    Principal Investigator: Christine Katlama
    Germany
    Medizinische Klinik und Poliklinik Universitätsklinikum Bonn Not yet recruiting
    Bonn, Germany
    Contact: Juergen Rockstroh
    Principal Investigator: Juergen Rockstroh
    Goethe University Hospital Frankfurt Not yet recruiting
    Frankfurt, Germany
    Contact: Christoph Stephan
    Principal Investigator: Christoph Stephan
    ICH Study Center Gmbh & Co. KG Not yet recruiting
    Hamburg, Germany
    Contact: Hans-Jürgen Stellbrink
    Principal Investigator: Hans-Jürgen Stellbrink
    Medizinische Hochschule Hannover Not yet recruiting
    Hannover, Germany
    Contact: Georg Behrens
    Principal Investigator: Georg Behrens
    Sub-Investigator: Mattias Stoll
    University Hospital Klinikum rechts der Isar der TUM Not yet recruiting
    Munich, Germany
    Contact: Christoph Spinner
    Principal Investigator: Christoph Spinner
    Ireland
    Mater Misericordiae University Hospital Not yet recruiting
    Dublin, Ireland
    Contact: Patrick Mallon
    Principal Investigator: Patrick Mallon
    St Vincent's University Hospital Not yet recruiting
    Dublin, Ireland
    Contact: Patrick Mallon
    Principal Investigator: Patrick Mallon
    Italy
    Università di Brescia Not yet recruiting
    Brescia, Italy
    Contact: Francesco Castelli
    Principal Investigator: Francesco Castelli
    ASST Santi Paolo Not yet recruiting
    Milano, Italy
    Contact: Antonella d'Arminio Monforte
    Principal Investigator: Antonella d'Arminio Monforte
    Luigi Sacco Hospital Not yet recruiting
    Milan, Italy
    Contact: Stefano Rusconi
    Principal Investigator: Stefano Rusconi
    Ospedale San Raffaele Not yet recruiting
    Milan, Italy
    Contact: Antonella Castagna
    Principal Investigator: Antonella Castagna
    Clinica of Infectious Diseases Not yet recruiting
    Modena, Italy
    Contact: Giovanni Guaraldi
    Principal Investigator: Giovanni Guaraldi
    INMI Lazzaro Spallanzani, Rome Not yet recruiting
    Rome, Italy
    Contact: Andrea Antinori
    Principal Investigator: Andrea Antinori
    Spain
    Hospital General Universatario Alicante Not yet recruiting
    Alicante, Spain
    Contact: Joaquín Portilla Sogorb
    Principal Investigator: Joaquín Portilla Sogorb
    Hospital Clinic (Helios Building) Recruiting
    Barcelona, Spain
    Contact: Josep Mallolas
    Principal Investigator: Josep Mallolas
    Hospital de la Santa Creu i Sant Pau Not yet recruiting
    Barcelona, Spain
    Contact: Pere Domingo
    Principal Investigator: Pere Domingo
    Hospital Universitari Vall d'Herbon Not yet recruiting
    Barcelona, Spain
    Contact: Adrian Curran
    Principal Investigator: Adrian Curran
    Hospital General Universitatrio de Elche Recruiting
    Elche, Spain
    Contact: Mar Masia
    Principal Investigator: Mar Masia
    Hospital Ramon y Cajal Not yet recruiting
    Madrid, Spain
    Contact: José Luis Casado Osorio
    Principal Investigator: José Luis Casado Osorio
    Hospital Universitatrio La Paz Not yet recruiting
    Madrid, Spain
    Contact: Ignacio Perez Valero
    Principal Investigator: Ignacio Perez Valero
    United Kingdom
    Royal Bournemouth Hospital Recruiting
    Bournemouth, United Kingdom
    Contact: Elbushra Herieka
    Principal Investigator: Elbushra Herieka
    Southmead Hospital Recruiting
    Bristol, United Kingdom
    Contact: Mark Gompels
    Principal Investigator: Mark Gompels
    Leeds Teaching Hospital Recruiting
    Leeds, United Kingdom
    Contact: Jane Minton
    Principal Investigator: Jane Minton
    Barts Health Recruiting
    London, United Kingdom
    Contact: Chloe Orkin
    Principal Investigator: Chloe Orkin
    Chelsea and Westminister Recruiting
    London, United Kingdom
    Contact: Alessia Dalla Pria
    Principal Investigator: Alessia Dalla Pria
    Guy's Hospital Recruiting
    London, United Kingdom
    Contact: Julie Fox
    Principal Investigator: Julie Fox
    Homerton University Hospital Recruiting
    London, United Kingdom
    Contact: Iain Reeves
    Principal Investigator: Iain Reeves
    Imperial College Healthcare Trust Recruiting
    London, United Kingdom
    Contact: Alan Winston
    Principal Investigator: Alan Winston
    Kings College London Recruiting
    London, United Kingdom
    Contact: Frank Post
    Principal Investigator: Frank Post
    Mortimer Market Centre Recruiting
    London, United Kingdom
    Contact: Rob Miller
    Principal Investigator: Rob Miller
    Royal Free Hospital Recruiting
    London, United Kingdom
    Contact: Margaret Johnson
    Principal Investigator: Margaret Johnson
    St George's Hospital Not yet recruiting
    London, United Kingdom
    Contact: Lisa Hamzah
    Principal Investigator: Lisa Hamzah
    University Hospital Lewisham Recruiting
    London, United Kingdom
    Contact: Stephen Kegg
    Principal Investigator: Stephen Kegg
    North Manchester General Hospital Recruiting
    Manchester, United Kingdom
    Contact: Andrew Ustianowski
    Principal Investigator: Andrew Ustianowski
    Sheffield Teaching Hospital Not yet recruiting
    Sheffield, United Kingdom
    Contact: Karen Rogstad
    Principal Investigator: Karen Rogstad

    Sponsors and Collaborators

    NEAT ID Foundation
    Gilead Sciences
    Janssen Pharmaceuticals

    Investigators

    Study Director: Georg Behrens Hannover Medical School
    More Information

    More Information


    Responsible Party: NEAT ID Foundation  
    ClinicalTrials.gov Identifier: NCT03696160   History of Changes  
    Other Study ID Numbers: NEAT44  
    Study First Received: September 24, 2018  
    Last Updated: August 27, 2019  
    Individual Participant Data    
    Plan to Share IPD: Undecided  

    Studies a U.S. FDA-regulated Drug Product: No  
    Studies a U.S. FDA-regulated Device Product: No  
    Product Manufactured in and Exported from the U.S.: No  

    Additional relevant MeSH terms:
    Protease Inhibitors
    Integrase Inhibitors

    ClinicalTrials.gov processed this data on October 15, 2019
    This information is provided by ClinicalTrials.gov.