HIV-1 infection MedDRA version: 20.1 Level: LLT Classification code 10000808 Term: Acute human immunodeficiency virus type I infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Juluca 50 mg/25 mg film-coated tablets dolutegravir/rilpivirine
Product Name: Dolutegravir 50mg / 25mgRilpivirine FDC
Product Code: DTG+RPV FDC
Pharmaceutical Form: Tablet
INN or Proposed
Sponsors
European AIDS Treatment Network Infectious Disease Foundation (NEAT ID)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is male or female aged 18 years or over. 2. Has documented HIV-1 infection 3. Is capable of giving informed consent, or if appropriate, subjects having an acceptable individual capable of giving consent on the subject’s behalf. 4. Is willing to comply with the protocol requirements 5. Virologically suppressed (plasma HIV-RNA 24 weeks) and on a stable regimen. 6. Subjects are required to have a history of the K103N mutation. 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. Study sites may ask the coordinating centre for advice as required. 7. Subjects must have never failed INSTI (2 x VL >200 >2 weeks apart) but current regimen can include INSTI. 8. A female, may be eligible to enter and participate in the study if she: a. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and = 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, b. is of child-bearing potential with a negative pregnancy test at Screening (& baseline visit) and agrees to use one of the following methods of contraception to avoid pregnancy: • True abstinence from penile-vaginal intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications (When this is in line with the preferred and usual lifestyle of the subject.) (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception]. • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide); • Any intrauterine device (IUD) with published data showing that the expected failure rate is =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Infected with HIV-2 2. Detectable HIV-1 RNA at screening (HIV-1 RNA measurement >=50 c/mL). 3. 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. 4. Use of medications which are associated with Torsades de Pointes 5. 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). 6. Unstable health conditions (i.e. opportunistic infections, cancers, unstable liver disease etc). 7. 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 35% direct bilirubin) 21. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbum
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare efficacy of DTG/RPV combined tablet versus continued antiretroviral treatment regimen at 48 weeks in individuals with the K103N resistance mutation.;Secondary Objective: To investigate whether switching patients to DTG/RPV FDC is associated with improvement of lipid profile, patient satisfaction, quality of life and potential for drug-drug interactions, investigated over time through 96 weeks with evaluation (and comparison to control arm) at week 24, 48 and 96. To evaluate DTG & RPV concentrations in blood. To evaluate changes in cell associated virus.;Primary end point(s): 1. Virological suppression (50 copies at least 2 weeks apart, investigated over 96 weeks.;Timepoint(s) of evaluation of this end point: Virological suppression after 48 weeks Virological failure after 96 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1a. Proportion of participants with plasma HIV-1 RNA <50 c/mL at week 24, 48 and 96. b. Changes in laboratory parameter from baseline c. Changes in renal markers, bone markers, and fasting lipids from baseline, week 24, week 48 and week 96. d. Resistance in failures (descriptive analysis) and baseline factors associated with failures. e. Changes in QoL and patient satisfaction from baseline. f. Number of participants with adverse events (AEs), Severity of AEs, and treatment discontinuations due to AEs. g. Number of potential DDIs avoided. h. Virological suppression (<200 copies/ml HIV RNA) at week 24, 48, 96 in individuals with previous NNRTIs virological failure and/or baseline transmitted resistance with the k103N resistance mutation, switching to DTG/RPV FDC. Analysed in line with FDA Snapshot method. i. Pre-dose plasma concentrations of DTG and RPV at week 4 (experimental arm only), 48 (experimental arm only) & 96. Plus pre/post-dose (as appropriate) at early termination visit and /or in the event of virological failure (see section 6.12) a post dose sample will be taken within 20-28 hours. j. Changes in cell associated virus using PBMC Illumina MiSeq sequencing at week 48 and week 96.;Timepoint(s) of evaluation of this end point: 24, 48 & 96 weeks | — |
Countries
Belgium, France, Germany, Italy, Spain, United Kingdom
Contacts
Public ContactAssociate Director
European AIDS Treatment Network Infectious Disease Foundation (NEAT ID)
Outcome results
None listed