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Clinical Trials

Date: 2017-02-13

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the Conference on Retroviruses and Opportunistic Infections (CROI)

Company: ViiV Healthcare (UK - USA) Janssen Pharmaceutical , a J&J company (USA - NJ)

Product: dolutegravir (Tivicay®) and rilpivirine (Edurant®)

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. 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.
  • Rilpivirine (Edurant®) is a non-nucleoside reverse transcriptase inhibitor.

Disease: HIV-1 infection

Therapeutic area: Infectious diseases

Country: USA

Trial details:

  • The Phase III program evaluates the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed with a three- or four-drug regimen. In the clinical trials, dolutegravir and rilpivirine are provided as individual tablets. SWORD-1 and SWORD-2 are replicate 148-week, randomised, open-label, non-inferiority studies to assess the antiviral activity and safety of a two-drug regimen of DTG + RPV compared with current antiretroviral therapy. Each study seeks to enrol approximately 500 patients across 13 countries and aims to enrol meaningful numbers of patients from groups underrepresented in HIV clinical studies, such as women and people over 50 years of age. The primary endpoint is proportion of patients with plasma HIV-1 RNA <50 copies per milliliter (c/mL) at Week 48. Key secondary endpoints include evaluation of the development of viral resistance, measurements of safety and tolerability, and changes in renal, bone and cardiovascular biomarkers. (NCT02429791 and NCT02422797)

Latest news:

  • • On February 13, 2017, Janssen Sciences Ireland announced positive results from the full data read out for two Phase III studies evaluating the safety and efficacy of switching virologically suppressed patients from a three- or four-drug antiretroviral regimen to the two-drug regimen of dolutegravir (ViiV Healthcare) and rilpivirine (Janssen). Full results were presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, WA. The dolutegravir and rilpivirine regimen achieved non-inferior viral suppression (HIV-1 RNA <50 c/mL) at 48 weeks compared with a three- or four-drug regimen in both pooled and individual analyses of the SWORD 1 and SWORD 2 studies (current antiretroviral therapy (CAR) 485/511 (95%), dolutegravir + rilpivirine 486/513 (95%) (adjusted difference -0.2%, (95% CI: [3.0%, 2.5%]), pooled analysis). Virologic suppression rates were similar between treatment arms. The median duration of antiretroviral treatment was just over four years at the time of entry into the studies. The most commonly reported (>5%) adverse events in the dolutegravir and rilpivirine arm were nasopharyngitis, headache, diarrhea and upper respiratory tract infection. For the CAR arm, the most commonly reported adverse events were nasopharyngitis, upper respiratory tract infection, back pain, headache and diarrhea. The studies are ongoing for 148 weeks.
  • Virologic failure rates were <1% in the DTG+RPV arm and 1% in the three- or four- antiretroviral-drug arm. No integrase strand inhibitor (INSTI) resistance-associated mutations were reported. Protocol-defined virologic failure with a non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutation (RAMs; K101K/E) was reported in only one patient in the DTG+RPV arm in the context of documented non-adherence, but with no impact on regimen efficacy as the subject re-suppressed on dolutegravir and rilpivirine prior to withdrawal from the study.
  • The overall rate of serious adverse events was comparable between treatment groups (DTG+RPV: 27, CAR: 21). As would be expected when switching from a stable regimen to a new regimen (in most cases containing two new drugs), more adverse events were reported and led to withdrawal from the study in the DTG+RPV arm (DTG+RPV: 21, CAR: 3). The safety profiles for dolutegravir and rilpivirine in these studies were consistent with the product labelling for each medicine. If approved, this treatment could be the first two-drug regimen for HIV and could offer those living with HIV who are virally suppressed the option to switch to a regimen which does not include a nucleotide reverse transcriptase inhibitor (NRTI).
  • • On May 6, 2015, ViiV Healthcare announced the start of a phase III clinical trial programme to evaluate the safety and efficacy of dolutegravir (Tivicay®) and rilpivirine (Edurant®) as maintenance therapy for adult patients with HIV. The phase III programme comprises two replicate studies evaluating 48 week viral suppression with a two drug regimen combining an integrase inhibitor (dolutegravir) and a non-nucleoside reverse transcriptase inhibitor (rilpivirine) in patients with HIV who have already achieved viral suppression with a three drug regimen. The phase III programme will evaluate the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current INI-,NNRTI-, or PI-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed. In the clinical trials, dolutegravir and rilpivirine will be provided as individual tablets; development of the single-tablet formulation will be concurrent with conduct of the trials.
  • In June 2014, ViiV Healthcare and Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson announced a partnership to investigate the potential of combining dolutegravir and rilpivirine in a single-tablet in order to expand the treatment options available to people living with HIV.

Is general: Yes