Clinical Trials

Date: 2018-07-24

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the 22nd International AIDS conference

Company: ViiV Healthcare (UK - USA)

Product: dolutegravir and lamivudine

Action mechanism:

• integrase inhibitor/non-nucleoside reverse transcriptase inhibitor. Dolutegravir is an investigational integrase inhibitor (INI). 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.

Disease: HIV-1 infection in adults

Therapeutic area: Infectious diseases

Country: Argentina, Australia, Belgium, Canada, France, Germany, Italy, Republic of Korea, Mexico, Netherlands, Portugal, Romania, Russian Federation, Spain, Taiwan, UK, USA

Trial details:

• GEMINI 1 (204861) and GEMINI 2 (205543) are duplicate, phase III, randomised, double-blind, multicentre, parallel group, non-inferiority studies. These studies evaluate a two-drug regimen of dolutegravir and lamivudine compared with a standard three-drug, first-line regimen in HIV-1 infected, antiretroviral therapy (ART)-naïve adult participantswith baseline viral loads less than 500,000 copies per ml. The studies are designed to demonstrate the non-inferior efficacy, safety, and tolerability of once-daily dolutegravir and lamivudine compared to once-daily dolutegravir and the fixed-dose combination of TDF/FDC at 48 weeks in HIV-1-infected, ART-naïve participants. (NCT02831673 (GEMINI 1) - NCT02831764 (GEMINI 2)
• The GEMINI studies are part of ViiV Healthcare’s innovative clinical trial programme for two-drug regimens that seeks to address long-term toxicity concerns of people living with HIV by reducing the number of medicines used in their treatment. The studies together include approximately 1,400 men and women living with HIV and are being conducted at research centres in Europe, Central and South America, North America, South Africa and Asia Pacific.

Latest news:

• • On July 24, 2018 ,ViiV Healthcare presented at the 22nd International AIDS conference in Amsterdam 48-week results from the phase III GEMINI 1 & 2 studies, assessing the safety and efficacy of a two-drug regimen (2DR) of dolutegravir (DTG) and lamivudine (3TC) compared to a three-drug regimen of dolutegravir and two nucleoside reverse transcriptase inhibitors (NRTIs), tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment-naïve, HIV-1 infected adults with baseline viral loads up to 500,000 copies per millilitre (c/mL).
• The studies met their primary endpoint for non-inferiority based on plasma HIV-1 RNA <50c/mL, a standard measure of HIV control, at Week 48. In a pooled analysis, 91% (655/716) of patients taking DTG + 3TC had HIV-1 RNA<50 copies/mL compared with 93% (669/717) of patients taking DTG +TDF/FTC [adjusted difference -1.7% (95% CI: -4.4%, 1.1%)].
• Results show broadly consistent results for virus suppression across individuals with higher viral load (more than 100,000 copies of viral RNA per millilitre of blood plasma [>100,000 c/mL]) and lower viral load (<=100,000 c/mL) HIV-1 plasma RNA.Rates of virologic failure were ?1% across all arms of the study. No patient who experienced virologic failure in either treatment arm developed treatment-emergent resistance.
• The percentage of patients that withdrew due to adverse events was 2% in each study arm (GEMINI 1 DTG + 3TC arm: n=7, GEMINI 1 DTG + TDF/FTC arm n=8, GEMINI 2 DTG + 3TC arm n= 8, GEMINI 2 DTG + TDF/FTC arm n = 8). Pooled results show that the most common (?5%) adverse events across the studies were headache, diarrhoea and nasopharyngitis in both arms (DTG + 3TC arm: 10%, 9%, and 8%, respectively, DTG + TDF/FTC: 10%, 11%, and 11%, respectively).
• Drug-related adverse events were less frequent in patients on the DTG/3TC regimen (126/716, 18%), compared with those on the DTG + TDF/FTC regimen (169/717, 24%).
• ViiV Healthcare intends to seek regulatory approval for a fixed-dose combination of DTG and 3TC later this year. DTG and 3TC, as a 2DR, is not yet approved for use by the US FDA.
• • On June 14, 2018, ViiV Healthcare announced positive headline results from its phase III GEMINI study programme. The studies (GEMINI-1 and GEMINI-2) are designed to evaluate the safety and efficacy of a two-drug regimen (2DR) of dolutegravir and lamivudine compared to a three-drug regimen of dolutegravir and two nucleoside reverse transcriptase inhibitors, tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), in treatment naïve HIV-1 infected adults with baseline viral loads less than 500,000 copies per ml.
• The studies met their primary endpoint for non-inferiority based on plasma HIV-1 RNA <50 copies per millilitre (c/mL), a standard measure of HIV control, at Week 48. The safety results for the 2DR of dolutegravir and lamivudine were consistent with the product labelling for the medicines. No patient who experienced virologic failure in either treatment arm developed treatment-emergent resistance.
• Full results from the studies will be presented at an upcoming scientific meeting. ViiV Healthcare will now plan for regulatory submissions for the two-drug regimen of dolutegravir and lamivudine later this year.

   

Is general: Yes