Primary: To demonstrate the non-inferior antiviral activity of switching to DTG + RPV once daily compared to continuation of current antiretroviral regimen (CAR) over 48 weeks in HIV-1 infected antiretroviral therapy (ART) experienced subjects.…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
% of subjects with plasma HIV-1 RNA <50 copies/mL at week 48.
Secondary outcome
CD4+ lymphocyte count, % of subjects with plasma HIV-1 RNA <50 copies/mL at
week 24, adverse events, premature discontinuation rate, change in biomarkers
and lipids, incidence of resistance, pre-dose plasma concentrations. Previously
mentioned variables by 3rd agent treatment class. Symptom distress module, HIV
TSQ,
Background summary
There has been much discussion of NRTI-sparing regimens for long-term treatment
of HIV infection as a possible approach to avoid known NRTI-associated adverse
drug reactions and long-term toxicities. In addition, while there are no
currently approved two-drug regimens to maintain suppression, simplifying
treatment has long been a goal to increase treatment compliance and improve the
quality of life for patients with HIV. The overall objective of the clinical
development program of dolutegravir (DTG) + rilpivirine (RPV) is to develop a
FDC tablet. In addition to this goal, two-drug combination therapy with DTG +
RPV may also offer a better tolerability and resistance profile without the
requirement for a PK booster in virologically suppressed, treatment-experienced
subjects.
Study 201636 is being conducted to establish if HIV-1 infected adult subjects
with current virologic suppression on a regimen with 2 NRTIs + a third agent
remain suppressed upon switching to a two-drug regimen with DTG + RPV.
Study objective
Primary: To demonstrate the non-inferior antiviral activity of switching to DTG
+ RPV once daily compared to continuation of current antiretroviral regimen
(CAR) over 48 weeks in HIV-1 infected antiretroviral therapy (ART) experienced
subjects.
Secondary: immunological activity, antiviral activity, safety and tolerability,
biomarkers (renal, bone, CV), effects on lipids, viral resistance, trough
plasma concentrations, impact of baseline 3rd agent treatment class (INI,
NNRTI, PI) on efficacy and safety, treatment satisfaction.
Study design
Randomized open-label phase III parallel group non-inferiority study.
Randomization (1:1) to:
• DTG + RPV once daily;
• CAR (with 2 NRTIs + a 3rd agent).
Stratification by baseline 3rd agent.
At week 52 patients on CAR will also be switched to DTG + RPV.
Total duration148 weeks.
476 subjects.
Subjects who have fully completed the study may continue with DTG + RPV until
the combination is commercially available or until development is discontinued.
Intervention
Treatment with
• DTG + RPV or
• 2 NRTIs plus a 3rd agent (INI, NNRTI or a PI), followed by DTG + RPV.
Study burden and risks
Risk: adverse events of study treatment.
Burden:
Visits: 10 visits in the 1st year, 6 visits in the 2nd year and every 12 weeks
thereafter.
Physical examination nearly every visit.
Blood tests during nearly every visit until week 148 (approx. 35-95 ml per
visit), thereof 6 times fasting.
Urine tests 6 times.
ECG at screening.
Questionnaires (1-4).
Optional: genetic testing (6 ml of blood, once).
Great West Road 980
Brentford Middlesex TW8 9GS
GB
Great West Road 980
Brentford Middlesex TW8 9GS
GB
Listed location countries
Age
Inclusion criteria
• HIV1-infected males and females, 18 years and above.
• Uninterrupted current regimen (either the initial or second cART regimen) for at least 6 months.
Acceptable stable cART regimens prior to Screening include 2 NRTIs plus:
• INI
• NNRTI
• PI
See protocol section 5.1 (inclusion criteria) for details.
• Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening.
• Plasma HIV-1 RNA <50 c/mL at Screening.
• Females of childbearing potential: adequate method of contraception during study, see protocol section 5.1, item 5.
Exclusion criteria
• Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement >=50 c/mL
• Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL or 2 or more plasma HIV-1 RNA measurements >=50 c/mL.
• Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening. Exceptions: see protocol section 5.2, item 4..
• Any switch to a 2nd line regimen due to virologic failure to therapy. See protocol section 5.2, item 5 for details.
• Pregnancy or breastfeeding.
• Any evidence of an active CDC Category C disease. Exceptions: see protocol section 5.2, item 7 for details.
• Severe hepatic impairement, unstable liver disease, evidence of Hepatitis B virus. See protocol section 5.2, item 8 for details.
• Exclusionary treatments: medications associated with Torsades de Pointes, HIV-1 immunotherapeutic vaccine, radiation therapy, cytotoxic chemotherapeutic agents, any immunomodulators that alter immune responses, experimental drug or vaccine, any regimen consisting of only single NNRTI therapy or only single or dual NRTI therapy prior to starting cART, ETR, prohibited medication listed in protocol section 6.8.2. See protocol section 5.2, item 17-25 and 6.8.2 for details (e.g. interval until screening).
• Evidence of viral resistance. See protocol section 5.2, item 26 for details.
• Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-005147-40-NL |
| CCMO | NL53023.100.15 |
| Other | viiv-clinicalstudyregister.com 201636 |