Marechal Thaumaturgo

Researchers are studying the safety and tolerability of budoprutug, a humanized monoclonal antibody that targets CD19 cells, in adults with primary membranous nephropathy (PMN). This Phase 2, open-label, multicenter trial focuses on patients who are anti-PLA2R antibody positive and continue to have proteinuria despite optimized RAAS inhibition. The study aims to evaluate three different intravenous dose regimens of budoprutug and their effects on this specific kidney condition. Participants will receive budoprutug through single intravenous doses on Day 1, Day 15, Day 169, and Day 183 within one of three sequential dose groups. Approximately 45 subjects will be enrolled, each receiving treatment according to their assigned dosing schedule. The study includes a follow-up period through Week 48, with additional monitoring for B-cell recovery as needed. During the study, participants will undergo safety assessments including monitoring for treatment-emergent adverse events up to 48 weeks. Researchers will also evaluate pharmacodynamics and preliminary efficacy through laboratory tests and clinical evaluations. Regular visits will include tests for kidney function, protein levels in urine, and blood cell counts, alongside other health assessments to ensure participant safety and gather data on how the drug affects the disease.

Researchers are evaluating the antiviral activity of multiple influenza drugs in adults with early symptomatic influenza infection. This Phase 2, randomized, open-label, controlled, adaptive platform trial aims to compare the effectiveness of currently licensed influenza antivirals and those with potential antiviral activity against a no-treatment control group. The study focuses on patients with uncomplicated influenza who have high viral loads, to better understand in-vivo antiviral effects and support guideline development and treatment prioritization. The trial includes several licensed antiviral drugs such as oseltamivir, peramivir, zanamivir, laninamivir, baloxavir, and favipiravir, along with molnupiravir, which has shown antiviral activity in pre-clinical studies. Treatments are administered in various forms including oral, inhaled, and intravenous routes, with dosing schedules ranging from single doses to multiple days of twice-daily dosing. Some treatment arms combine two antivirals. Randomization ensures at least 20% of participants receive no antiviral treatment, with equal allocation among available interventions. Participants will be involved from screening through treatment and monitoring up to five days, during which the rate of viral clearance will be measured. Assessments include symptom evaluation, rapid antigen or RT-PCR testing to confirm influenza infection, and safety monitoring. Participants must be able to walk unaided and adhere to study procedures, including follow-up visits. The overall study duration covers early infection and antiviral response measurement, focusing on understanding drug effects in uncomplicated flu cases.

Researchers are evaluating the effectiveness and safety of zanidatamab combined with a physician's choice of chemotherapy compared to trastuzumab combined with chemotherapy in treating adults with metastatic HER2-positive breast cancer. This study focuses on participants whose cancer has progressed or who cannot tolerate previous treatment with trastuzumab deruxtecan (T-DXd). The study is a phase 3 randomized trial aiming to assess progression-free survival and other important outcomes such as patient-reported tolerability and physical functioning. Participants receive either zanidatamab or trastuzumab through intravenous infusion, alongside chemotherapy drugs chosen by their physician from eribulin, gemcitabine, vinorelbine (all intravenous), or oral capecitabine. The study includes detailed monitoring of drug safety and how the body processes zanidatamab. The treatments continue until disease progression or unacceptable side effects occur. During the study, participants undergo regular evaluations including scans to measure cancer progression according to RECIST guidelines. Researchers also monitor safety through laboratory tests and heart function assessments. Participants are followed for up to approximately 44 months to measure progression-free survival and overall treatment outcomes. Long-term follow-up and patient-reported outcomes help provide a complete understanding of the treatments' effects.

Researchers are evaluating PBFT02, a gene therapy designed to treat frontotemporal dementia (FTD) in adults who have mutations in the granulin precursor (GRN) or C9ORF72 genes. This study aims to assess the safety, tolerability, and effectiveness of delivering a functional GRN gene copy directly to the brain. The trial includes participants aged 35 to 75 years with early symptomatic FTD caused by these genetic mutations. PBFT02 is delivered as a one-time injection into the cisterna magna using an adeno-associated viral vector. The study is open-label, multicenter, and involves multiple cohorts: three for FTD-GRN and two for FTD-C9orf72. The treatment is given once, followed by a 5-year study period divided into a 2-year main study and a 3-year safety extension to monitor long-term effects. During the study, participants will undergo repeated assessments including nerve conduction studies and blood tests to measure immune responses against the gene therapy vector and transgene. Researchers will track treatment-related adverse events and serious adverse events over up to five years with multiple visits. The study evaluates changes in nerve function and immune response, along with ongoing safety monitoring to understand the therapy's impact over time.

This research aims to evaluate how well Debio 4126 maintains insulin-like growth factor 1 (IGF-1) levels at or below the upper limit of normal in adults with acromegaly who have been previously treated with somatostatin analogs. The study is a Phase 3 randomized trial comparing Debio 4126 to a placebo to assess its efficacy and safety. Acromegaly is a condition characterized by excessive growth hormone, and controlling IGF-1 levels is important for managing the disease. Participants will receive either Debio 4126, which is a 12-week extended-release formulation of octreotide given by intramuscular injection, or a placebo injection of mannitol suspension. The study includes a double-blind period where neither participants nor researchers know who receives the active drug or placebo. There is also an open-label period where all participants may receive Debio 4126. The treatment schedule involves injections every 12 weeks. During the study, participants will be monitored to measure the percentage who maintain IGF-1 levels at or below the upper limit of normal at week 36. Researchers will assess safety and efficacy through various evaluations including laboratory tests and clinical assessments. The study also requires participants to meet certain health criteria before and during the trial to ensure safety and reliable results. The total study timeline includes these treatment and observation periods as defined by the protocol.

Researchers are evaluating whether the medicine vicadrostat, combined with empagliflozin, helps adults with chronic heart failure (HF) who have a weakened heart pumping function, specifically a left ventricular ejection fraction (LVEF) below 40%. Eligible participants must have been diagnosed with chronic HF at least 3 months before joining. The study is a Phase III trial designed to compare the effects of vicadrostat plus empagliflozin against placebo plus empagliflozin in people with symptomatic chronic HF classified as New York Heart Association classes II to IV. Participants are randomly assigned to one of two groups. One group takes tablets containing vicadrostat and empagliflozin, while the other group takes placebo tablets that look like vicadrostat along with empagliflozin. Tablets are taken once daily for a period ranging from about 6 months up to about 3.5 years. Participants continue their usual heart failure treatments during the study. The study is double-blind, meaning neither the participants nor the study staff know who is receiving which treatment. During the study, participants regularly visit the study site or may have phone contacts for follow-up. They answer questions about their health and well-being. Doctors monitor and record any worsening of heart failure symptoms, hospital visits due to heart failure, or deaths. They also check participants' overall health and note any side effects. The main outcome measured is the time until a participant experiences cardiovascular death, hospitalization for heart failure, or an urgent heart failure visit, over up to 43 months of follow-up.

Researchers are conducting a multicenter, national, prospective cohort study to evaluate the effectiveness and safety of tisagenlecleucel therapy in Brazilian patients with B-cell malignancies such as Acute Lymphoblastic Leukemia (ALL), Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL). This observational study will include both pediatric and adult patients who have received tisagenlecleucel through commercial or out-of-specification use in Brazil. The study aims to collect data over up to 15 years to better understand long-term outcomes for these patients. The study involves no new treatment allocation or mandatory administration of study drugs. Instead, it observes patients who have already received tisagenlecleucel. Data will be gathered retrospectively and prospectively, covering a "pre-infusion" period from diagnosis until just before infusion, and a "post-infusion follow-up" period for up to 15 years after receiving tisagenlecleucel. Approximately 200 patients are expected to be enrolled over 5 years. Participants will be followed through medical records and data collection until death or their last scheduled visit. Researchers will monitor various outcomes including overall response rates, duration of response, relapse-free survival, event-free survival for ALL patients, progression-free survival for DLBCL patients, overall survival, and hematologic recovery for ALL patients. No additional treatments or questionnaires are mandated by the study protocol, focusing instead on gathering real-world data about the long-term effects and safety of tisagenlecleucel.

Researchers are evaluating antiviral treatments in adults aged 18 to 60 with early symptomatic COVID-19 who have high viral loads but are otherwise healthy. This phase 2, multi-center, adaptive platform trial aims to measure the antiviral effects of several interventions compared to no treatment, focusing on how quickly the virus clears from the body within the first five days. The study includes small molecule drugs, monoclonal antibodies, and dose-finding for parts of nirmatrelvir/ritonavir to understand their effectiveness in vivo. The trial investigates multiple antiviral treatments including small molecule drugs such as nitazoxanide, nirmatrelvir/ritonavir, hydroxychloroquine, atilotrelvir/ritonavir, and metformin; monoclonal antibodies like sotrovimab, tixagevimab/cilgavimab, and casirivimab/imdevimab; and combination therapies. Participants are randomly assigned to receive one of these treatments or no antiviral treatment (with at least 20% assigned to no treatment). Dosages and schedules vary by treatment, for example, nirmatrelvir/ritonavir is given twice daily for five days, while monoclonal antibodies are given once on day 0. Participants will be involved in assessments including viral clearance measurements over days 0 to 5. Researchers will monitor for viral load reduction as the primary outcome, comparing treated groups to controls. Participants must be able to walk unaided, have oxygen saturation of at least 96%, and agree to follow-up visits. Safety and treatment adherence are monitored throughout, with the study supported by the Wellcome Trust and conducted under controlled conditions to ensure accurate evaluation of antiviral effects.

Researchers are exploring how very early intensive antiretroviral therapy (ART), with or without a broadly neutralizing antibody (bNAb), may help infants living with HIV achieve HIV remission, defined as having HIV RNA levels below the detection limit of the test. This Phase I/II study focuses on infants born to mothers with presumed or confirmed HIV infection and aims to evaluate the impact of starting treatment within 48 hours of birth. The study includes two groups: infants born to mothers who received little or no antiretrovirals during pregnancy, and infants confirmed HIV positive shortly after birth who started ART quickly. The study tests seven different intensive therapy regimens involving combinations of nucleoside reverse transcriptase inhibitors (NRTIs), nevirapine (NVP), lopinavir/ritonavir (LPV/r), raltegravir (RAL), dolutegravir (DTG), and monoclonal antibodies VRC01 or VRC07-523LS. Treatments are given orally or by subcutaneous injection depending on the drug. The study is conducted in four steps: initial enrollment and evaluation within 48 hours of birth (Step 1), up to 192 weeks of ART treatment with monitoring and possible treatment interruption if virus suppression is achieved (Step 2), close monitoring during treatment interruption for up to five years (Step 3), and re-initiation of ART with ongoing monitoring if the virus returns or other criteria are met (Step 4). Participants will be closely monitored throughout the study with regular HIV testing, physical exams, and assessments of immune health. Safety monitoring will continue for infants who do not have confirmed infection but received initial treatment. Children who maintain viral suppression will undergo analytic treatment interruption and be followed for viral rebound. Outcome measures include the number of participants who reach HIV remission by week 48. The study may last up to five years for some participants, including long-term follow-up through re-treatment and viral monitoring.