MK-8527 / Merck (MSD) - LARVOL DELTA

A Study of MK-8527 in Healthy Lactating Female Participants (MK-8527-009) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

A Study of Carbamazepine (CBZ) and MK-8527 in Healthy Adult Participants (MK-8527-012) (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of MK-8527 in Healthy Adult Participants (MK-8527-013) (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of Carbamazepine (CBZ) and MK-8527 in Healthy Adult Participants (MK-8527-012) (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Study of Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) and MK-8527 in Healthy Participants (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed

MK-8527 PK/PD Threshold and Phase II Dose Selection for Monthly Oral HIV-1 Preexposure Prophylaxis (CROI 2025) - "Three oral dose levels of MK-8527 (3, 6, and 12 mg, administered monthly) were selected for the Phase 2 study. Conclusions PK/PD results incorporating clinical and nonclinical data support efficacy and further development of MK-8527 doses up to 12 mg for monthly oral PrEP."

Late-breaking abstract • P2 data • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

Safety and Pharmacokinetic Study of Oral MK-8527 QM in Participants at Low-Risk for HIV-1 Infection (MK-8527-007) (clinicaltrials.gov) - P2 | N=352 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

A Study of Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) and MK-8527 in Healthy Participants (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of MK-8527 in Healthy Adult Participants (MK-8527-013) (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Study of Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) and MK-8527 in Healthy Participants (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial

A Study of MK-8527 in Participants With Moderate and Severe Renal Impairment (MK-8527-008) (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Renal Disease

A Drug-Drug Interaction Study of MK 8527 With a Combined Oral Contraceptive (LNG/EE) (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Merck Sharp & Dohme LLC

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

A Study of MK-8527 in Participants With Moderate and Severe Renal Impairment (MK-8527-008) (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Renal Disease

Drug-agnostic transcutaneously-refillable subdermal implant for ultra-long-acting delivery of antiretrovirals for HIV prevention (HIVR4P 2024) - "Here we present a drug-agnostic transcutaneously-refillable subdermal implant for ultra-long-acting controlled delivery of potent ARVs, with a primary focus on islatravir (ISL) and MK-8527. The subdermal implant comprises of a biocompatible titanium casing acting as the drug reservoir, internally mounted with a silicon nanochannel membrane to control release...Further, the implants were evaluated for in vivo release of MK-8527, lenacapavir (LEN), bictegravir (BIC), and other hydrophobic ARVs. Sustained ultra-long release of ISL from the subdermal implant was shown through stable plasma and peripheral mononuclear blood cells drug levels for over 29 months in NHP without fluctuation or implant refilling... Our ultra long-acting subdermal implant offers safe and effective long-lasting protection against HIV, where minimally-invasive transcutaneous refillability extends release potentially throughout the recipient's lifespan. Implant drug-agnosticity imparts flexibility..."

Late-breaking abstract • Human Immunodeficiency Virus • Infectious Disease

Weekly oral prophylaxis with MK-8527 protects rhesus macaques from rectal challenge with simian-human immunodeficiency virus (HIVR4P 2024) - "MK-8527 provides complete protection in the rhesus macaque intrarectal challenge model supporting its continued clinical development as an HIV prophylactic agent."

Human Immunodeficiency Virus • Infectious Disease

A Study of MK-8527 in Healthy Lactating Female Participants (MK-8527-009) (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial • Human Immunodeficiency Virus • Infectious Disease

Phase 1, open-label study to evaluate the drug interaction between MK-8527, an HIV-1 nucleoside reverse transcriptase translocation inhibitor, and the oral contraceptive levonorgestrel/ethinyl estradiol in healthy adult females (AIDS 2024) - "The study evaluated the potential for any DDI of LNG/EE with MK-8527 to allow the use of hormonal contraceptives without dose adjustment in individuals receiving MK-8527. Coadministration of a single dose of MK-8527 with LNG/EE was generally well tolerated; further pharmacokinetics results to be presented at the conference."

Clinical • P1 data • Gynecology • Hematological Disorders • Human Immunodeficiency Virus • Infectious Disease

A Study of MK-8527 in Participants With Moderate and Severe Renal Impairment (MK-8527-008) (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Renal Disease

Safety and Pharmacokinetic Study of Oral MK-8527 QM in Participants at Low-Risk for HIV-1 Infection (MK-8527-007) (clinicaltrials.gov) - P2 | N=350 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

Discovery of MK-8527: A Long-Acting HIV-1 Nucleoside Reverse Transcriptase Translocation Inhibitor (CROI 2024) - "Background: Nucleoside reverse transcriptase translocation inhibitors (NRTTIs) such as islatravir (ISL) are potent inhibitors of HIV-1 replication. The subnanomolar potency, absence of off-target activity, and suitable PK for at least once-weekly dosing make MK-8527 an attractive clinical candidate for prophylaxis of HIV-1 infection"

Human Immunodeficiency Virus • Infectious Disease

Single Dose Administration of MK-8527, a Novel nRTTI, in Adults With HIV-1 (CROI 2024) - P1 | "In treatment-naive persons with HIV-1, single doses of MK-8527 as low as 0.5 mg achieved ≥1 log10 decreases in HIV-1 RNA at Day 7 following dose administration."

Clinical • Human Immunodeficiency Virus • Infectious Disease

Safety and Pharmacokinetics of MK-8527, a Novel nRTTI, in Adults Without HIV (CROI 2024) - "Single (0.5–200 mg) and multiple (QW) doses (up to 40 mg) of MK-8527 administered to adults without HIV were generally well tolerated. The safety and pharmacokinetic profiles of MK-8527 support continued clinical investigation."

Clinical • PK/PD data • Human Immunodeficiency Virus • Infectious Disease

A Study of MK-8527 in Participants With Moderate and Severe Renal Impairment (MK-8527-008) (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P1 trial • Renal Disease

MK-8527 Single-Dose Trial in HIV-1 Infected Participants (MK-8527-004) (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Islatravir: evaluation of clinical development for HIV and HBV. (PubMed, Expert Opin Investig Drugs) - "Islatravir (ISL) is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that inhibits HIV RT through multiple mechanisms. Additionally, MK-8527, which inhibits HIV via same mechanism as that of ISL may supersede ISL. Data on ISL inhibition of HBV are scarce, and preclinical data show dramatically lower ISL efficacy against HBV than currently preferred nucleos(t)ide drugs, indicating that ISL may not be a potent anti-HBV drug."

Journal • Human Immunodeficiency Virus • Infectious Disease