The Late Presenter Treatment Optimisation Study (LAPTOP)
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|ClinicalTrials.gov Identifier: NCT03696160|
Recruitment Status : Recruiting
First Posted : October 4, 2018
Last Update Posted : August 28, 2019
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 or disease||Intervention/treatment||Phase|
|HIV/AIDS||Drug: Biktarvy Drug: Symtuza||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||440 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||March 5, 2019|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||December 2021|
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.
Integrase inhibitor used to treat HIV-1 infection
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.
Protease inhibitor used to treat HIV-1 infection
- 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
- 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
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03696160
|Contact: LAPTOP Project Manager||+44 203 859 firstname.lastname@example.org|
|Contact: LAPTOP Project Manager||+44 203 859 email@example.com|
|Study Director:||Georg Behrens||Hannover Medical School|