|Activity of Dolutegravir (DTG) 50mg BID versus Placebo (PBO)
over 7 Days of Functional Monotherapy in Patients Harbouring Raltegravir and/or
Elvitegravir Resistance Virus: Primary Endpoint Results of the VIKING-4 Study
|B. Akil1, G. Blick2, D. Hagins3, M. Ramgopal4, G. Richmond5, R. Samuel6, N. Givens7, C. Vavro8, B. Wynne9, M. Ait-Khaled7, for the VIKING-4 Study Team|
|1Chelsea Village Medical, P.C., New York, United States, 2Circle Care Center, Norwalk, United States, 3Chatham County Health Department, Savannah, United States, 4Midway Immunology and Research Center, Fort Pierce, United States, 5Gary J. Richmond, M.D.,P.A., Fort Lauderdale, United States, 6Temple University, Philadelphia, United States, 7GlaxoSmithKlilne, London, United Kingdom, 8GlaxoSmithKline, Research Triangle Park, United States, 9GlaxoSmithKline, Philadelphia, United States|
|Objectives: DTG 50mg BID efficacy in RAL/EVG resistant patients was demonstrated in the VIKING-3 open-label, single arm study. The uncontrolled design may not exclude the potential contribution of failing ARTs to the observed Day 8 response (Mean= -1.43 log10 c/mL). The VIKING-4 study which includes a placebo-controlled phase was conducted to address this issue.|
Methods: VIKING-4 is a Phase III, randomised, double-blind, placebo-controlled, superiority study. Thirty ART-experienced adults, with Screening resistance to RAL/EVG and to ≥ two other ART classes, were randomised to DTG 50mg BID or PBO while continuing their failing regimen (without RAL/EVG). From Day 8, all patients received open-label DTG with an optimised regimen. The Day 8 antiviral activity and safety/tolerability data are presented.
Results: Patients were highly ART-experienced with a 14 years prior median ART duration comprising a median 15 prior ARVs. The proportion of Q148 viruses at Baseline was higher in VIKING-4 DTG arm (9/14; 64%) than in VIKING-3 (57/183; 31%). The DTG Day 8 mean change from Baseline in Plasma HIV-1 RNA was statistically superior to that of PBO.
| || ||Mean* Change from Baseline in Plasma HIV-1 RNA at Day 8 (log10 c/mL)||Standard Error||Difference**||95% CI for difference||p-value|
|Placebo||16||+0.10||0.183|| || || |
|*Primary endpoint: Mean (LOCFDB, ITT-E population), adjusted for Baseline plasma HIV-1 RNA, Baseline DTG FC, OSS of failing regimen and the interaction between DTG FC in susceptibility and treatment. Means and differences calculated using the average Baseline DTG FC of the whole ITTE population.|
|**Superiority of DTG over PBO demonstrated with upper bound of 95% CI below 0 and p<0.05.|
|***One patient (DTG arm) had no result for baseline DTG FC and hence was excluded from the analysis.|
[Mean Change from Baseline in HIV-1 RNA at Day 8]
DTG activity was consistent between studies. The Day 8 mean response was best for viruses without Q148 mutation: -1.43 log10
c/mL (n=5) in VIKING-4 and -1.59 log10
c/mL (n=126) in VIKING-3. Response for viruses with 'Q148 + 1' and 'Q148+ ≥2' mutations was lower [-0.9 log10
c/mL for each (n=6 and n=3 respectively)] and similar to VIKING-3 (Nichols et al. HIV11, Glasgow. Abstract O232). The most frequent AEs were diarrhoea (4/30), nausea (4/30) and headache (4/30), 5 subjects developed a SAE (one fatal), all considered unrelated to study drug.Conclusion:
Superior Day 8 antiviral activity of DTG vs. PBO confirms that activity was attributable to DTG and not to the failing regimen. DTG activity was consistent with the larger VIKING-3 pivotal Phase III study results.
Mounir Ait-Khaled , GlaxoSmithKlilne , London , United Kingdom
Assigned in sessions:
17.10.2013, 12:00-14:00, Poster Session, Poster Session 1, Exhibition
18.10.2013, 12:00-14:00, Poster Session, Poster Session 2, Exhibition