Clinical Trials

Date: 2013-03-06

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta, Georgia

Company: ViiV Healthcare (UK-USA) Shionogi (Japan)

Product: dolutegravir

Action mechanism:

• Dolutegravir is an investigational integrase inhibitor (INI) currently in development by Shionogi-ViiV Healthcare LLC for the treatment of HIV. It is currently the only once-daily, unboosted INI in Phase III clinical development. Integrase inhibitors block HIV replication by  preventing the viral DNA from integrating into the genetic material of human immune cells (T-cells). This step is essential in the HIV replication cycle and is also responsible for establishing chronic infection. Given the stage of development of this investigational HIV therapy, the full picture of the efficacy and safety of dolutegravir has not been conclusively determined.

Disease: Hiv-Aids

Therapeutic area: Infectious diseases

Country:

Trial details:

• VIKING-3 (ING112574) is an ongoing Phase III, multicentre, open-label, single arm study to assess the antiviral activity and safety of  dolutegravir 50mg twice-daily in treatment-experienced adults with HIV-1 and historical or current evidence of resistance to raltegravir or elvitegravir. SAILING (ING111762) is an ongoing Phase III, multicentre, double blind, double dummy study to compare the efficacy and safety of dolutegravir 50mg once-daily to raltegravir 400mg twice-daily in treatment-experienced, integrase inhibitor-naive adults with HIV-1. SPRING-2 (ING113086) is an ongoing Phase III, multicentre, double blind, double dummy study to compare the efficacy and safety of dolutegravir 50mg once-daily to  raltegravir 400mg twice-daily in treatment-naïve adults with HIV-1. Full  48-week data from SPRING-2 were presented at the International AIDS Conference in July 2012. SINGLE (ING114467) is an ongoing Phase III, multicentre, double blind, double dummy study to compare the efficacy and safety of once-daily dolutegravir 50mg plus abacavir/lamivudine versus Atripla® (tenofovir/emtricitabine/efavirenz). Full 48-week data from SINGLE were presented at ICAAC in September 2012. Together with data from an ongoing bioequivalence study (ING114580) , SINGLE is designed to support additional regulatory submissions for a fixed dose combination of dolutegravir/abacavir/lamivudine.

Latest news:

• • On March 6, 2013, ViiV Healthcare has announced 24-week data from the Phase III SAILING (ING111762) study evaluating the investigational integrase inhibitor dolutegravir in patients with HIV-1 who are failing on current therapy, but had not been treated with an integrase inhibitor. The SAILING study was designed to demonstrate non-inferiority of a regimen containing dolutegravir versus raltegravir (both with up to two background agents) and the analysis met this criterion; statistical superiority was concluded as part of a pre-specified testing procedure. At 24 weeks, 79% of study participants receiving the once-daily dolutegravir regimen were virologically suppressed (HIV-1 RNA <50 c/mL) vs. 70% of participants on the twice-daily raltegravir regimen. This difference in response was statistically significant with a 95% confidence interval for the difference of 3.4% to 15.9% (p=0.003). Differences in treatment outcome in favour of the dolutegravir arm were driven by greater virologic response: at Week 24, 15% of patients receiving the dolutegravir regimen had virologic non-response vs. 24% of patients receiving the raltegravir regimen. In addition, fewer subjects failed therapy with integrase inhibitor resistance on dolutegravir (n=2) than on raltegravir (n=10, p=0.016). Overall, the tolerability of dolutegravir (DTG) was similar to that of raltegravir (RAL). At 24 weeks, 2% of subjects on the dolutegravir regimen discontinued due to adverse events (AEs) vs. 4% of subjects on the raltegravir regimen. The rate of drug-related AEs was similar for both arms (DTG 20%, RAL 23%) and commonly reported AEs (defined as events that occurred in more than 10% of subjects) were similar on both arms, namely diarrhoea (20% DTG, 17% RAL) and upper respiratory tract infection (11% DTG, 8% RAL). The primary objective of the ongoing double-blind, double-dummy phase III SAILING study is to demonstrate the antiviral activity of once-daily dolutegravir 50mg compared to twice-daily raltegravir 400mg over 48 weeks in HIV-1 infected, antiretroviral-experienced, integrase inhibitor-naïve adults. At baseline, 715 study participants were randomised 1:1 to receive either dolutegravir or raltegravir plus investigator-selected background regimen of no more than 2 agents, one of which was fully active. All subjects had documented genotypic or phenotypic resistance to agents from at least two antiretroviral therapy drug classes, and ongoing virologic replication. Median baseline HIV-1 RNA levels were 4.18 log10 c/mL and median baseline CD4+ cell counts were 200 cells/mm3. The study population included 32% women, 42% were of African American/African heritage, and 46% of study participants were classified as CDC Class C (patients who have one or more AIDS-defining illness). The 48-week primary analysis of this study will be presented at a future scientific meeting.
• • On October 4, 2012, Shionogi-ViiV Healthcare has announced that the phase III data required for initial regulatory filings of the investigational integrase inhibitor dolutegravir in adults infected with HIV are in house. Data from the two phase III studies in treatment-experienced patients (VIKING-3 and SAILING) have been received and will be the subject of future presentations at scientific meetings. Together with previously disclosed data from the SPRING-2 and SINGLE studies in treatment-naive patients, these additional study data support Shionogi-ViiV Healthcare’s plans to commence global regulatory submissions for dolutegravir before the end of 2012. Several results from SPRING2 have been already reported and full results of  the VIKING-3 and SAILING studies in treatment-experienced adults with HIV-1 will be presented at upcoming scientific meetings.

Is general: Yes