Dose Ranging Trial of MK-8591 Given in Combination Therapy

• Research type

  Research Study

• Full title

  A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose- Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination with Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults

• IRAS ID

  234555

• Contact name

  Andrew Ustianowski

• Contact email

  Andrew.Ustianowski@pat.nhs.uk

• Sponsor organisation

  Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Eudract number

  2017-000437-32

• Duration of Study in the UK

  3 years, 4 months, 0 days

• Research summary

  Summary of Research
  Human immunodeficiency virus (HIV) infection, which causes acquired immunodeficiency syndrome (AIDS), is a disease associated with substantial complications and mortality but can be controlled through life-long antiretroviral therapy (ART). Nucleoside reverse transcriptase inhibitors (NRTIs), Non-NRTIs (NNRTIs), protease inhibitors, fusion inhibitors, co-receptor antagonists and integrase strand transfer inhibitors are all classes of ART. Although successful combinations of ART generally utilize 3 agents from at least 2 different classes, there is a need to improve on the safety and tolerability of ART.

  While ART can delay disease progression, death and reduce the risk of HIV transmission, it does not cure HIV. ART aims to suppress HIV to undetectable levels so that the body’s immune function is preserved or restored.
  MK-8591 is a novel HIV-1 nucleoside reverse transcriptase translocation inhibitor (NRTTI), being developed HIV-1 infection treatment, which blocks HIV reverse transcriptase by a novel dual mechanism of action. MK-8591 is different from other HIV-1 treatments because of its high potency, favourable drug profile and broad distribution in the body.
  Doravirine (DOR) is a novel NNRTI and is differentiated by its activity against mutations that confer resistance to other NNRTIs, low potential for drug-drug interactions, promising efficacy, low likelihood of selection for viral resistance and good tolerability. Whilst Lamivudine (3TC), is a well-tolerated NRTI that is already approved for treatment of HIV in combination with other antiretroviral agents. The comparator in this trial is MK-1439A.

  The study will last approximately 3 years and evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of MK-8591 given daily in combination with DOR and 3TC. Approximately 120 male/female participants (≥ 18 years) will be enrolled and randomised to one of four treatment groups.

  The study is funded by Merck Sharp & Dohme Limited and will take place at 5 study centres in the UK.

  Summary of Research
  https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbRehJ-2Fi4xyo44sEgJVCl5BcbW9wgc64X2JjNxW-2BqMpAMvOXZd10tc7pf49dilWrMwYdZ5lQ3A7FARUCBl-2Byd0sp73qdl-2BhcrGwmg9DdNb0YSMMOY_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YLctHUXUdsJTI5oOr38eBN1gTIwqHIzYWQ-2Fh50HwUVb782nQt0v-2BGxrvKqBihExeG4hlygsGt-2B-2FdhoZQLWGQCEAcCtJ-2FYxsNtX4ce0LoaLZa-2BZkvE-2BdbS21hA5vzQ1aPfdSV4aEILuTZJ-2FHRxUEFa2sXPTX-2FJ7-2BNABQV4jbpWsBrg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7Cd81eed601f784e1692f808db40da3273%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638175078109432505%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=lH8TZLTwUkGtppWlcJ%2BT5ykiz7qV0cBWP7DfBVNA04Y%3D&reserved=0

• REC name

  East of England - Cambridge South Research Ethics Committee

• REC reference

  17/EE/0431

• Date of REC Opinion

  18 Dec 2017

• REC opinion

  Further Information Favourable Opinion