Manaus

Researchers are looking for new medicines to prevent HIV-1 (Human Immunodeficiency Virus Type 1) infection. The goals of this study are to learn: * If taking MK-8527 once a month works to prevent HIV-1 infection as well as or better than a standard (usual) pre-exposure prophylaxis (PrEP) taken once a day * About the safety of MK-8527 and if people tolerate it

Researchers are evaluating a revised weight-based dose of tafenoquine for treating vivax malaria. This Phase 3 trial aims to determine if the revised tafenoquine regimen, targeting 7.5 mg per kg of body weight, is not less effective than a high dose of primaquine (7 mg/kg over 7 days), and if it is better than a fixed 300 mg dose of tafenoquine. The study also looks at whether this revised dosing is safe, tolerable, and practical for patients. Participants will receive oral treatment with either the revised weight-based tafenoquine dose, fixed dose tafenoquine, or high dose primaquine. The study compares these groups to assess safety and effectiveness. Treatment dosing is adjusted based on weight bands to reach the target dose in the revised tafenoquine group. During the trial, researchers will monitor participants for four months to measure the risk of vivax parasitaemia returning. Participants will be followed for six months in total, with assessments including clinical monitoring and safety evaluations. The study focuses on ensuring the revised tafenoquine dose is both effective and well tolerated in patients with vivax malaria.

This research aims to evaluate the safety and effectiveness of iza-bren, a bi-specific antibody-drug conjugate targeting EGFR and HER3 with a topoisomerase inhibitor, compared to the treatment of physician's choice (paclitaxel, nab-paclitaxel, carboplatin plus gemcitabine, or capecitabine). The study focuses on patients with previously untreated, locally advanced, recurrent inoperable, or metastatic triple-negative breast cancer (TNBC) or estrogen receptor (ER)-low, HER2-negative breast cancer who are not eligible for anti-PD(L)1 or endocrine therapies. The trial is conducted in two phases, phase 2 and phase 3, to thoroughly assess these treatments.

Researchers are evaluating the safety and effectiveness of combining valemetostat tosylate with pembrolizumab compared to pembrolizumab alone in adults with advanced or metastatic non-small cell lung cancer (NSCLC) that has no actionable genomic alterations and whose tumors show high PD-L1 expression (50% or greater). This trial includes participants who have not previously received systemic therapy for their advanced or metastatic NSCLC. The study is conducted in two phases: a dose escalation phase to find the recommended phase 2 dose, followed by a dose expansion phase to further assess treatment effects. Participants receive valemetostat tosylate orally once daily until the recommended dose is established. Pembrolizumab is given as an intravenous infusion on the first day of each 21-day cycle, for up to 35 cycles. The trial compares this combination treatment to pembrolizumab alone, administered on the same schedule. The study design is open-label and randomized, allowing comparison of both treatment approaches in this patient population. During the study, participants undergo regular assessments including imaging scans to measure disease progression and safety monitoring for side effects. Researchers track dose-limiting toxicities, treatment-related adverse events, and progression-free survival over approximately 31 months. Tumor tissue samples and biomarker analyses are collected to support evaluation. Participant physical status and eligibility are carefully assessed before and during the study. Follow-up includes monitoring for safety up to 30 days after the last dose and long-term evaluation of treatment impact.

This research aims to evaluate the effects of EYU688 on dengue viral load, fever clearance time, and clinical signs and symptoms in patients diagnosed with dengue fever. It is a phase 2 randomized, participant- and investigator-blinded, placebo-controlled study that investigates both the efficacy and safety of orally administered EYU688 compared with a matching placebo. The study includes two parallel cohorts with different pharmacokinetic (PK) sampling schedules: an intensive PK cohort and a sparse PK sampling cohort. Participants will receive either EYU688 or placebo capsules administered orally. The treatment is given to patients who have confirmed dengue fever symptoms and a positive dengue test, with the onset of fever within 48 hours prior to starting treatment. The two cohorts run simultaneously but differ based on the frequency and intensity of PK blood sampling to assess drug behavior in the body. Throughout the study, participants will be monitored for changes in viral load measured at 48 hours after treatment begins, as well as fever duration and clinical symptoms. Assessments include laboratory tests to evaluate safety and efficacy, with careful monitoring for any adverse effects. The total duration of participation includes screening, treatment, and follow-up evaluations to ensure comprehensive data collection on the drug's impact and participant safety.

Researchers are evaluating the use of adjuvant chemotherapy in patients with locally advanced cervical cancer who test positive for cell-free human papillomavirus deoxyribonucleic acid (cfHPV-DNA) in their plasma after standard treatment. This Phase 3, randomized, multicenter clinical trial aims to determine if patients with persistent cfHPV-DNA expression after chemoradiotherapy can benefit from additional chemotherapy. The study includes patients with cervical cancer stages IB3 to IVA who have completed standard concomitant chemoradiotherapy.

Researchers are evaluating the effect of muvalaplin on reducing cardiovascular risk in adults with elevated lipoprotein(a) levels who either have atherosclerotic cardiovascular disease or are at risk for a heart attack or stroke. This Phase 3, randomized, double-blind, placebo-controlled study focuses on adults with high Lp(a) levels and prior or potential cardiovascular events. The study aims to assess the time to the first major adverse cardiovascular event over about 5.25 years. Participants will be randomly assigned to receive either muvalaplin or a placebo, both administered orally. The study includes individuals with Lp(a) levels of at least 175 nanomoles per liter who have had a prior cardiovascular event within 10 years or are at risk for a first event due to conditions such as coronary artery disease, carotid stenosis, peripheral artery disease, high coronary artery calcium score, reduced kidney function with diabetes, or other high-risk factors. The treatment period lasts through the study duration, with close monitoring. During the study, participants will be regularly evaluated to track the occurrence of major adverse cardiovascular events, including heart attacks and strokes. Safety assessments will monitor blood pressure, kidney function, and heart failure status among other health indicators. The primary outcome measures the time to the first major cardiovascular event from baseline up to the end of the study, which spans approximately 5.25 years.

This research aims to study treatment options for people living with both HIV-1 and tuberculosis (TB), focusing on those who have not yet received antiretroviral therapy (ART). Tuberculosis is a leading cause of death among people with HIV worldwide, and starting ART soon after beginning TB treatment improves survival. The study evaluates a dual therapy regimen combining dolutegravir and lamivudine compared to the standard treatment using dolutegravir with two other drugs, following current guidelines on timing ART initiation based on CD4 counts. Participants are randomly assigned to one of three groups: one receiving a dual therapy of dolutegravir plus lamivudine twice daily, another receiving a combination of dolutegravir/lamivudine (Dovato) in the morning plus dolutegravir in the evening, and a third group receiving the standard twice-daily dolutegravir plus tenofovir disoproxil fumarate/lamivudine. All participants are also on rifampin-based TB treatment. This Phase IIIb multicenter international trial compares the safety, tolerability, and effectiveness of these regimens. Participants will be monitored for HIV viral suppression at 28 weeks using established laboratory tests. Researchers will collect data on treatment safety and tolerability throughout the study. The trial includes detailed assessments such as CD4 counts, viral load measurements, and confirmation of TB diagnosis, with follow-up visits to track progress and monitor side effects. The total study duration and additional follow-up details are aligned with the treatment period for HIV and TB co-infection.

Researchers are investigating whether the medicine vicadrostat, when taken together with empagliflozin, can lower the risk of heart-related problems in adults who have type 2 diabetes, high blood pressure, and cardiovascular disease but no history of heart failure. This study is a Phase III trial that compares the effects of vicadrostat plus empagliflozin to a placebo plus empagliflozin in people with these conditions. Participants are randomly assigned to one of two groups: one group takes vicadrostat and empagliflozin tablets, and the other group takes placebo tablets that look like vicadrostat along with empagliflozin. All participants take one tablet daily for a period ranging from two and a half years up to four years and three months. Throughout the study, participants continue their usual medications for diabetes, high blood pressure, and cardiovascular disease. During up to 51 months of participation, participants visit the study site regularly where doctors collect health information and blood samples. Researchers track when participants experience cardiovascular events such as heart-related deaths or heart failure events. The study also monitors participants’ overall health and any side effects they may experience to assess the safety and effects of the treatments.

Researchers are evaluating how well long-acting lenacapavir works to prevent HIV infection in people at higher risk in Brazil. This study also looks at the safety of lenacapavir, how many participants continue using their chosen prevention method over time, and whether people prefer this option compared to daily oral pre-exposure prophylaxis (PrEP). The study compares two prevention options: long-acting lenacapavir injections given every six months and daily oral PrEP pills containing tenofovir disoproxil fumarate and emtricitabine. Participants choose their preferred prevention method after counseling, and the study follows them for up to two years. About 1200 participants choosing lenacapavir will receive an oral loading dose over the first eight days, followed by subcutaneous injections every six months for up to two years, totaling up to four injections. Around 300 participants choosing oral PrEP will take a daily pill continuously for up to 24 months. Both groups will have regular clinic visits for HIV testing, safety assessments, STI screening and treatment, prevention counseling, and monitoring of medication adherence and side effects. During the study, participants will visit clinics regularly for HIV testing, health checkups, and prevention counseling. Researchers will monitor how well participants stay on their chosen prevention method and record any adverse events or injection site reactions. The main outcomes measured include how many remain on lenacapavir at 24 months and the time until stopping lenacapavir. The study aims to help health services in Brazil improve HIV prevention options and support for people wanting to prevent HIV infection.