Paarl

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study to see if it can reduce the risk of major adverse cardiovascular events (MACE-PLUS) in adults with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for a first ASCVD event. The study compares AZD0780 to a placebo and monitors participants from randomization until the primary analysis censoring date, followed by a final study closure visit. Participants will be randomly assigned to receive either oral AZD0780 or an oral placebo once daily. The treatment period lasts until the primary analysis censoring date, after which a study closure visit will occur. The study is event-driven and designed to assess the time to the first major cardiovascular event during treatment. During the study, participants will be closely monitored with various assessments to evaluate cardiovascular outcomes and safety over approximately 54 months. Researchers will track the time to first event of any component of MACE-PLUS and collect data to assess the effect of AZD0780 compared to placebo. The study includes regular visits and evaluations to ensure participant safety and adherence to treatment.

Researchers are evaluating the effectiveness and safety of Datopotamab Deruxtecan (Dato-DXd) with or without durvalumab compared to the investigator's choice chemotherapy combined with pembrolizumab in patients who have PD-L1 positive locally recurrent inoperable or metastatic triple-negative breast cancer (TNBC). This Phase III, randomized, open-label, international study aims to see if adding durvalumab to Dato-DXd can help patients live longer without their cancer worsening or simply live longer compared to standard chemotherapy with pembrolizumab. The study also examines how the treatments and cancer impact patients' quality of life. Participants will be randomly assigned to one of three treatment groups: Dato-DXd plus durvalumab, Dato-DXd alone, or investigator's choice chemotherapy (paclitaxel, nab-paclitaxel, or gemcitabine plus carboplatin) combined with pembrolizumab. All treatments are given by intravenous infusion. The study design includes stratification based on geographic location, disease-free interval history, and prior PD-1/PD-L1 treatment for early-stage TNBC. During the study, participants will have regular assessments to monitor their disease status using RECIST 1.1 criteria and undergo imaging reviewed by blinded independent central review. Researchers will track progression-free survival, quality of life, safety, and other health measures over an anticipated period of up to 33 months. Participants must provide tumor samples for PD-L1 testing, and safety monitoring will continue throughout the study.

Researchers are evaluating the effects of the drug orforglipron compared with a placebo on cardiovascular outcomes in adults who have atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). This is a Phase 3, randomized, double-blind, placebo-controlled study designed to investigate major adverse cardiovascular events over a long period. Participants will receive either orforglipron or a placebo orally. The study is event-driven and will continue until the occurrence of major cardiovascular events or up to about 5 years. The treatments are administered without revealing to participants which group they are in to ensure unbiased results. During the study, participants will be monitored for the time to the first occurrence of a major cardiovascular event. Researchers will collect data from baseline through the end of the study, which lasts approximately 5 years. Regular assessments will help evaluate the safety and effects of the treatments on cardiovascular health in this population.

This research aims to evaluate the antiviral effects of S-337395 compared with placebo in nonhospitalized adult participants who have symptomatic respiratory syncytial virus (RSV) infection and are at high risk of progressing to severe disease. The study focuses on adults with recent onset of RSV symptoms and important risk factors such as advanced age or chronic lung or cardiovascular disease. It is designed as a Phase 2b, randomized, double-blind, placebo-controlled trial to assess safety, tolerability, and efficacy. Participants will receive either S-337395 or a matching placebo according to a specified dosing schedule. The treatment begins within 72 hours of RSV symptom onset. The study measures changes in RSV viral RNA load from baseline to Days 2, 4, and 6 using nasopharyngeal swabs and quantitative reverse transcription polymerase chain reaction (qRT-PCR) tests to monitor antiviral effects. During the study, participants will be monitored for safety and effectiveness through viral load testing at multiple time points. Medical history, physical exams, vital signs, and ECGs are conducted to ensure stability aside from RSV symptoms. The study also tracks symptoms and any adverse events to evaluate treatment tolerability. Total participation includes screening and follow-up assessments as outlined by the study protocol.

Researchers are evaluating the safety, immune response, and effectiveness of a new tuberculosis vaccine called MTBVAC in healthy adolescents and adults aged 14 to 45 years who live in areas where TB is common. This Phase 2b study is randomized, double-blind, and placebo-controlled, involving participants with different immune responses to TB exposure as determined by IGRA testing. The study aims to protect against TB disease confirmed by multiple tests and focuses on those who are HIV-negative. Participants will be randomly assigned to receive either a single intradermal dose of the MTBVAC vaccine or a placebo. The vaccine dose contains approximately 5x10^5 colony-forming units, and the placebo is saline solution, both given as 0.1 mL injections. The study includes two groups based on IGRA status: one with prior immune response to TB and one without, with different randomization ratios. Some participants will be part of safety and immune response sub-cohorts for more detailed monitoring. Throughout the 36-month follow-up, participants will attend regular visits or be contacted to check for signs of TB. They will be trained to recognize TB symptoms and report them for further evaluation, including sputum testing using advanced molecular and culture methods. HIV testing will occur yearly and at times of suspected TB. Safety monitoring includes tracking adverse events and laboratory tests in selected subgroups. Participants diagnosed with TB will be referred for treatment according to local guidelines.

The purpose of the study is to evaluate whether ibuzatrelvir is effective and safe in adults and adolescents with COVID-19 who do not need to be in the hospital but who are at high risk for progression to severe disease. Eligible participants will be randomly assigned (by chance) to receive ibuzatrelvir or matching placebo orally for 5 days. Co-administration of locally available standard of care is allowed. The total duration of the study is around 6 months.

Researchers are evaluating continued access to study drugs for children and adolescents living with HIV-1 who completed participation in previous Gilead clinical studies. This open-label, single-arm Phase 4 study aims to provide these participants with ongoing treatment or switch them to a specific combination drug called bictegravir/emtricitabine/tenofovir (B/F/TAF). The study also monitors the safety of these HIV treatments in this population. Participants receive one of several oral medications including various doses of F/TAF, E/C/F/TAF, Cobicistat, B/F/TAF, or a third antiretroviral agent as determined by their investigator. Dosage forms include fixed-dose combination tablets and tablets for oral suspension, with doses adjusted as needed. Study drugs are provided continuously to eligible participants who completed prior Gilead parent studies. The study focuses on maintaining effective treatment while observing for any adverse effects. During the study, researchers track how many participants receive access to the study drugs over up to 9.5 years. Participants are monitored for side effects and safety through regular assessments. The study collects data on adverse events and laboratory results to evaluate how well the treatments are tolerated. This long-term follow-up helps understand safety in children and adolescents with HIV-1 receiving these therapies.

Researchers are evaluating the steady state pharmacokinetics, safety, and tolerability of doravirine (DOR) when given to pediatric participants with HIV-1 infection aged 4 weeks to less than 12 years and weighing under 45 kg. Participants may be treatment-naive or virologically suppressed on stable combination antiretroviral therapy (cART) with no history of treatment failure. This phase 2, single-group, open-label, multi-site study aims to assess DOR either with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or as part of a fixed-dose combination with lamivudine (3TC) and tenofovir disproxil fumarate (TDF). Participants receive oral doravirine combined with 2 NRTIs or as part of the fixed-dose combination DOR/3TC/TDF. The study includes a treatment period up to Week 24 to monitor pharmacokinetics and safety. Those who complete the Week 96 visit may join an extension study to continue receiving DOR until it becomes commercially available or for up to an additional 224 weeks, whichever occurs first. Throughout the study, participants undergo intensive pharmacokinetic sampling at designated timepoints up to 12 or 24 hours postdose to measure drug concentration and absorption parameters. Safety and tolerability are assessed through monitoring adverse events, laboratory tests, and clinical evaluations up to 24 weeks. Participants are closely observed for viral suppression status and any drug-related side effects during treatment and extension periods.

Researchers are evaluating a community-based hearing aid fitting service facilitated by community healthcare workers (CHWs) using mobile health (mHealth) technologies in low- and middle-income countries (LMICs). The study aims to determine if smartphone-based in-situ hearing aid fittings and pre-set hearing aid fittings provide better self-reported benefits compared to minimal amplification. This randomized controlled trial is designed to improve hearing care access in LMICs by assessing innovative, scalable approaches that address the scarcity of trained professionals and high costs of hearing care. Participants will be randomly assigned to one of three groups: an in-situ fitting group using Lexie Lumen hearing aids programmed with a proprietary algorithm based on the NAL-NL2 method via smartphone, a pre-set fitting group using Go Ultra hearing aids with four manual programs, or a control group receiving minimal amplification with Lexie Lumen hearing aids set at a flat 10 dB gain. The control group will cross over to the in-situ fitting after six weeks. All groups will receive a paper-based hearing aid support program and have access to CHWs for assistance. Participants will undergo baseline assessments including audiometric evaluation and otoscopy, followed by fitting and multiple follow-ups at 6, 12, 26, and 52 weeks. Outcome measures include self-reported benefits via the International Outcome Inventory for Hearing Aids (IOI-HA) and other questionnaires assessing hearing handicap, social network impact, and quality of life. Data collection is designed to minimize bias with administrative assistants gathering outcome measures. The total study duration per participant is approximately 52 weeks.

Researchers are evaluating the safety, tolerability, and effectiveness of long-acting lenacapavir (LEN) combined with other medicines in adolescents and children living with HIV-1 who weigh at least 35 kg and have previously been treated for HIV-1. The study focuses on treatment-experienced participants and aims to learn more about LEN's pharmacokinetics and safety when used alongside an optimized background regimen (OBR). Participants will receive LEN either as tablets taken without regard to food or as subcutaneous injections, combined with an optimized background regimen prescribed by the investigator. The study is open-label and single-arm, focusing on the effects of LEN combined with OBR over the course of the trial. During the study, participants will be monitored for LEN levels in their blood at Week 26, as well as for any treatment-emergent adverse events or laboratory abnormalities through Week 26. Researchers will assess the participants' health, laboratory tests, and side effects to better understand the drug's safety and antiviral activity. The study includes adolescents and children up to 17 years old who meet specific health criteria and treatment histories.