Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of … (NCT05349838) | Clinical Trial Compass
CompletedPhase 3
Open-Label Multi-Centre Randomised Switch Study to Evaluate Virological Efficacy Over 96Weeks Of 2-Drug Therapy With Dolutegravir(DTG)/Rilpivirine(RPV) Fixed Dose Combination(FDC) in Antiretroviral Treatment-Experienced HIV-1 Infected Subjects Virologically Suppressed With NNRTI Mutation K103N
Belgium, France140 participantsStarted 2018-11-05
Plain-language summary
HIV-1 infected subjects that experience virological failure while on non nucleoside reverse-transcriptase inhibitors (NNRTIs), including those with the K103N mutation, are usually switched to a boosted Protease Inhibitor (PI)-based regimen or other antiretroviral (ARV) combinations. The same is true for subjects who need to start antiretroviral therapy and have acquired virus that is already resistant to antiretrovirals. These "second line" combinations are often associated with numerous issues that can have a potential impact on the quality of life (QoL) of these patients. Therefore a simpler and better tolerated alternative second line treatment option would be a useful tool for the clinical management of these patients.
The aim of this study is to assess the efficacy and tolerability of a dual combined therapy of Dolutegravir (DTG) 50 mg Once Daily (OD) + Rilpivirine (RPV) 25 mg OD in virologically suppressed participants with previous virological failure with NNRTIs and having the clinically significant mutation K103N. The secondary objective of the study is to assess whether a simplification of the treatment in terms of pill burden, long term metabolic toxicity and potential for drug interactions improves the QOL of the participants. The study will also evaluate DTG \& RPV concentrations in the blood plus changes in cell associated virus.
In order to compare the first line treatment (boosted PI and/or other antiretroviral combinations) and the DTG+RPV combination, two thirds of study participants will be switched to DTG+RPV immediately and receive DTG+RPV for 96 weeks. The other third will be switched after 48 weeks of continuing on their first line treatment and receive DTG+RPV for 48 weeks. All participants will then be followed up for a further 30 days. Participants will be recruited from sites across Europe, and randomised onto either arm of the study. After randomisation, participants will attend approximately 10 visits over the course of two years.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Is male or female aged 18 years or over.
✓. Has documented HIV-1 infection
✓. Is capable of giving informed consent
✓. Is willing to comply with the protocol requirements
✓. Virologically suppressed (plasma HIV-RNA \<50 copies/mL for \>24 weeks) and on a stable regimen.
✓. Subjects are required to have a history of the K103N mutation (acquired or selected). Subjects who at any time have had the mutations 100I, 101E/P, 106A/M, 138K/G/Q, 181C/I/V, 188L, 190A/S/E/Q, 230L mutations are to be excluded. Other NNRTI region variants can be included. All PI and NRTI mutations are acceptable. Study sites may ask the coordinating centre for advice as required.
✓. Subjects must have never failed INSTI (2 x VL \>200 \>2 weeks apart) but current regimen can include Integrase Strand Transfer Inhibitor(INSTI).
✓. A female, may be eligible to enter and participate in the study if she:
Exclusion criteria
What they're measuring
1
Number of Participants With and Without Virological Suppression
✕. Subjects requiring regular dosing doing with H2 or PPI antacid medications or a history of achlorhidria or drug known to interact with RPV or DTG.
✕. Use of medications which are associated with Torsades de Pointes
✕. Corrected QT interval (QTc \[Bazett\]) \>450 milliseconds or QTc (Bazett) \>480 milliseconds for participants with bundle branch block. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB).
✕. Any evidence of an active Centers for Disease Control and Prevention Category C disease. Exceptions include cutaneous Kaposi's sarcoma not requiring systemic therapy and historic CD4+ lymphocyte counts of \<200 cells/millimeter3.
✕. History or presence of allergy to the study drugs or their components or drugs of their class;