Rostock

Researchers are evaluating the safety, tolerability, and therapeutic effects of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first-line treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC positive for human papilloma virus 16 HPV16 and expressing the protein PD-L1 with a combined positive score of 1 or higher. This is an open-label, multi-site, Phase IIIII clinical trial consisting of two parts an initial safety run-in phase and a randomized phase. In the safety run-in phase Part A, patients receive BNT113 in combination with pembrolizumab to confirm safety and tolerability at selected dose levels. The randomized phase Part B compares BNT113 combined with pembrolizumab against pembrolizumab monotherapy. Treatments are given by intravenous injection or infusion and continue for up to 24 months. An optional pre-screening phase allows tumor samples to be tested for HPV16 DNA and PD-L1 expression before the main trial screening. Participants will be closely monitored throughout the study. Assessments include safety evaluations, tumor response, and survival outcomes such as overall survival and progression-free survival. Tumor tissue samples must be provided for testing. Researchers will measure treatment-emergent adverse events, response rates, duration of response, and disease control. The study may last up to 48 months, with ongoing safety and efficacy monitoring during and after treatment.

Researchers are evaluating the efficacy and safety of volrustomig compared to observation in participants with unresected locally advanced head and neck squamous cell carcinoma LA-HNSCC who have not progressed after receiving definitive concurrent chemoradiotherapy cCRT. This phase III, randomized, open-label global study aims to assess whether volrustomig can improve outcomes in this patient population. Participants are randomly assigned to one of two groups those who receive volrustomig as sequential therapy, and those who undergo observation without additional treatment. The study compares these two approaches following prior curative concurrent chemoradiotherapy. The trial includes long-term follow-up to monitor patient outcomes. During the study, participants will be regularly assessed for progression-free survival, overall survival, physical functioning, and quality of life. Researchers will also monitor for the presence of anti-drug antibodies and adverse events related to volrustomig. Follow-up evaluations may continue for up to approximately eight years to fully understand the treatment impact and safety profile.

Researchers are conducting a master protocol study called OLMP to evaluate the safety and tolerability of different treatments for adults with Amyotrophic Lateral Sclerosis ALS. This study includes participants from an earlier study, OWAA, who will be assigned to specific treatment groups such as the Sporadic ALS OL01 substudy. The research aims to monitor treatment effects over at least 96 weeks. Participants in the OL01 substudy receive the investigational drug LY4256984 administered intrathecally directly into the spinal canal. This open-label extension study focuses on long-term safety and tolerability of LY4256984 in adults with ALS. The study is designed as a parallel interventional trial with no masking or placebo control. During the study, participants will be closely monitored for safety and treatment tolerance. The main outcome measured is the number of participants assigned to each intervention-specific appendix over the 96-week period. Participation involves ongoing assessments and follow-ups to track safety and tolerability, with the overall study lasting until June 2029.

This observational study follows patients with relapsing multiple sclerosis RMS who are being treated with approved injectable or selected oral disease-modifying therapies DMTs in Germany. The study is non-interventional and open-label, designed to collect real-world data on treatment and disease progression over several years. It aims to understand how patients continue their baseline treatments and how these treatments impact various health and quality of life measures. Participants receive routine medical care with approved injectable or oral DMTs such as ofatumumab, interferon b21, glatiramer acetate, teriflunomide, dimethyl fumarate, or diroximel fumarate. The study includes two cohorts with up to approximately two years of prospective observation each, with an optional extension allowing up to four years total. Treatment decisions and monitoring follow the patients usual care and physicians discretion, including routine visits and telemedicine options. During the study, participants provide medical history, complete questionnaires, and have data collected on disability status, MRI findings, relapses, and laboratory tests. Researchers assess treatment continuation rates, fatigue, anxiety, depression, quality of life, lesion counts, and relapse rates at multiple time points. Safety and treatment interruptions are also documented. Follow-up is flexible and based on standard care procedures, with data collection occurring throughout the observational periods.

Researchers are evaluating the real-world effectiveness, safety, and patient compliance of ribociclib combined with an aromatase inhibitor for adjuvant treatment in patients with hormone receptor-positive, HER2-negative early breast cancer at high risk of recurrence. This observational study also compares ribociclib treatment with abemaciclib plus endocrine therapy and endocrine therapy alone, aiming to better understand treatment decisions and clinical adoption in routine practice. The study is conducted across breast centers and gynecological practices to represent typical healthcare settings. Participants receive treatment based on their physicians clinical judgment without randomization or intervention assignment. The study collects data from patients treated with ribociclib plus aromatase inhibitor with or without luteinizing hormone-releasing hormone LHRH, abemaciclib plus endocrine therapy with or without LHRH, or endocrine therapy alone with or without LHRH. Baseline data and follow-up information on adverse events, quality of life, treatment adherence, and socio-economic factors are gathered over time. During the study, participants undergo assessments including evaluation of invasive disease-free survival up to 36 months, quality of life questionnaires, medication adherence reports, and monitoring of adverse events and treatment changes. Data on reasons for treatment decisions, patient perceptions, and healthcare provider involvement are also collected. The study duration extends up to 39 months to provide a comprehensive overview of treatment impact and patient experience in real-world clinical settings.

Researchers are conducting a prospective observational study to examine asthma control, health-related quality of life HRQL, lung function, and asthma medication use in patients with severe eosinophilic asthma treated with benralizumab in routine clinical practice settings in Germany. The study aims to gather real-world evidence on these patients over a 52-week period. Participants will be treated with benralizumab as part of their standard care, and no additional treatment will be assigned by the study. Asthma control will be assessed using the Asthma Control Test ACT and the Asthma Impairment and Risk Questionnaire AIRQae at various timepoints. Health-related quality of life will be measured using the mini Asthma Quality of Life Questionnaire miniAQLQ at baseline and follow-up visits. Patients will record their weekly asthma medication intake using either paper or electronic diaries throughout the study. During the study, participants will attend routine follow-up visits where investigators will collect clinical assessments and questionnaire data. Researchers will monitor changes in asthma control, lung function parameters, medication use, and patient-reported outcomes up to 52 weeks after the first dose of benralizumab. The primary outcomes include changes in ACT scores and inhaled corticosteroid use, while secondary outcomes cover remission criteria, lung function, biomarkers, exacerbation rates, and quality of life measures.

Researchers are evaluating ELVN-001, an investigational drug, in adults with chronic myeloid leukemia CML, including those with a specific T315I mutation. This early-phase trial aims to find safe and tolerable doses for further study, especially in patients who have relapsed, are resistant, or cannot tolerate current tyrosine kinase inhibitors TKIs. The study also examines how ELVN-001 affects disease markers and its overall safety profile. The trial includes a dose escalation phase to identify recommended doses, followed by dose expansion phases that treat patients with or without the T315I mutation at those doses. ELVN-001 is given orally once or twice daily. Participants receive the drug as a single agent, and the study monitors responses and safety during these phases. Participants will undergo regular assessments including monitoring for side effects, laboratory tests, heart evaluations, and measurement of molecular responses related to CML over periods ranging from 28 days up to 3 years. The study tracks drug levels in the body for up to 6 months and evaluates long-term outcomes such as complete blood responses. Overall participation duration varies, with close safety follow-up throughout.

Researchers are evaluating the combination of baxdrostat and dapagliflozin in people with chronic kidney disease CKD and high blood pressure hypertension. This Phase III, double-blind, placebo-controlled study aims to assess whether this combination reduces the risk of serious kidney damage, heart failure events, or cardiovascular death compared to dapagliflozin alone. The study includes participants with CKD and hypertension who meet specific kidney function and blood pressure criteria. Participants who are not already taking SGLT2 inhibitors will first complete a 4-week dapagliflozin run-in period. Then, they will be randomly assigned to receive either baxdrostat plus dapagliflozin or a placebo plus dapagliflozin. Baxdrostat dosing may start low and be increased if needed. Study visits will occur at 2, 4, 8, 16, 34, and 52 weeks after randomization, and then approximately every four months until the study ends, which is based on the number of key kidney or heart-related events. Throughout the study, participants will have regular assessments including blood tests to monitor kidney function and potassium levels, blood pressure measurements, and evaluations of heart and kidney health. If participants stop the blinded study drug early, they will continue dapagliflozin if possible and remain in the study for ongoing visits and monitoring. The main outcome is whether the combination treatment reduces the risk of a 50% sustained decline in kidney function, kidney failure, heart failure events, or cardiovascular death over up to 37 months.

Researchers are evaluating AZD0780, an oral PCSK9 inhibitor, in a phase 3, randomized, placebo-controlled study. This trial focuses on patients with established atherosclerotic cardiovascular disease ASCVD or those at high risk for a first ASCVD event. The study aims to assess how AZD0780 compares to placebo in reducing the risk of major adverse cardiovascular events, also known as MACE-PLUS, over the course of the trial. Participants are randomly assigned to receive either oral AZD0780 once daily or a matching placebo once daily. The study continues until a primary analysis censoring date, which may be up to approximately 54 months from randomization. After this, a study closure visit will be conducted as the final visit for each participant. During the study, participants will be regularly monitored for cardiovascular events including heart attacks, strokes, urgent coronary revascularizations, and other related outcomes. Researchers will track the time to first occurrence of these events as the primary outcome. Safety and other secondary outcomes like all-cause mortality will also be assessed. The total participation time can last up to about 54 months, with ongoing evaluations throughout this period.

Researchers are evaluating treatments for patients with high-risk chronic lymphocytic leukemia CLL, a type of blood cancer that is aggressive and currently incurable. This phase 3, open-label, multicenter, randomized study aims to compare the effectiveness of a triple drug combination acalabrutinib, obinutuzumab, and venetoclax against a double combination obinutuzumab and venetoclax in prolonging progression-free survival PFS for patients with specific high-risk genetic features such as 17p-deletion, TP53 mutation, complex karyotype, or unmutated IGHV gene status. The study addresses a crucial medical need for better treatments in this difficult-to-treat group. Participants will be randomly assigned to one of two treatment groups. One group receives the triple combination of acalabrutinib, obinutuzumab, and venetoclax, while the other group receives obinutuzumab plus venetoclax. Obinutuzumab is given as intravenous infusions on specific days across six cycles. Venetoclax is taken orally with a carefully planned dose escalation and maintenance over 12 cycles. Acalabrutinib is administered orally twice daily during cycles 15 to 24. The study explores whether adding acalabrutinib improves outcomes by using these fixed-duration, chemotherapy-free regimens. Throughout the study, participants will undergo regular assessments to monitor response and safety, including checks for minimal residual disease MRD and overall survival. These evaluations occur up to 50 months after the first patient is enrolled. Researchers will also track progression-free survival, complete and overall response rates, event-free survival, duration of response, and time to next treatment. Safety monitoring and laboratory tests will be performed as part of study visits. The total study participation is expected to last several years to capture long-term outcomes for this high-risk patient population.