Karlsruhe

Researchers are conducting a phase II, multicenter, open-label trial to investigate the combination of Fruquintinib and Tislelizumab in patients with microsatellite stable (MSS) or proficient mismatch repair (pMMR) metastatic colorectal cancer who do not have active liver metastases. The study aims to evaluate the effectiveness of this combination in comparison to a control treatment for this specific group of patients. Participants will be randomly assigned to one of two treatment groups. The experimental group will receive oral Fruquintinib (5 mg daily for 21 days in each 28-day cycle) along with intravenous Tislelizumab (400 mg every 42 days). The control group will be treated with oral Trifluridine/tipiracil (35 mg/m2 twice daily on days 1-5 and 8-12 of each 28-day cycle) plus intravenous Bevacizumab (5 mg/kg every 14 days). Treatment continues until disease progression, unacceptable side effects, patient choice, or a maximum of 15 months. During the study, patients will undergo regular assessments including imaging to monitor disease status and safety evaluations. Follow-up will continue for up to 18 months after the last patient enrolls or until death, withdrawal, or loss to follow-up. The main outcome measure is the efficacy of Fruquintinib combined with Tislelizumab in this patient population over a 54-month period.

Researchers are evaluating various approved injectable and oral disease-modifying treatments (DMTs) in patients with relapsing multiple sclerosis (RMS) in Germany. This observational, non-interventional, multicenter, open-label study collects primary data prospectively over up to four years, alongside retrospective data. The study captures medical history, disease duration, laboratory values, disability scores (EDSS), MRI results, and relapse information to provide real-world insights into treatment use and outcomes. Patients receiving routine medical treatment with any approved injectable or selected oral DMTs—including ofatumumab, glatiramer acetate, interferon 21, teriflunomide, dimethyl fumarate, and diroximel fumarate—are enrolled without treatment allocation by the study. Two cohorts are observed: one treated primarily with injectable DMTs and another with injectable or oral DMTs. The core study period lasts about two years, with an optional extension providing an additional two years of observation, totaling up to four years. Follow-up visits and monitoring happen at the investigator's discretion and may include telemedicine. During the study, participants provide data through questionnaires and electronic case report forms. Routine clinical care procedures, such as diagnostic tests and monitoring, continue as usual. Researchers measure the proportion of patients continuing their baseline treatment at 24 months and collect ongoing clinical and imaging data. The study emphasizes real-world treatment patterns, safety, and disease activity over the extended follow-up period.

Researchers are evaluating the clinical utility of serum neurofilament light (sNfL) as a prognostic marker for disease activity in patients with relapsing multiple sclerosis (MS). This prospective, multicenter, observational, non-interventional study in Germany aims to understand how sNfL values can influence patient management and treatment decisions. The study focuses on patients treated with category 1 disease-modifying therapies (DMTs) who have incorporated sNfL testing into their care. Participants will either continue their current category 1 DMT, which includes therapies such as dimethylfumarate, glatiramer acetate, interferon beta, and teriflunomide, or switch to ofatumumab based on their physician’s clinical judgment. There is no treatment allocation by the study itself. Data collection will cover up to 24 months, and the frequency of visits and assessments will follow routine clinical practice without a fixed protocol. During the study, baseline and follow-up data will be gathered according to standard care recommendations, including clinical evaluations and sNfL measurements. Researchers will monitor the proportion of patients with high sNfL levels over time to assess disease activity. The observational period is flexible and guided by the treating physician, with no additional diagnostic or monitoring procedures beyond standard care. Participants will be followed for up to two years to better understand how sNfL influences treatment management in relapsing MS.

Researchers are evaluating the real-world effectiveness, safety, and tolerability of ribociclib combined with an aromatase inhibitor, with or without luteinizing hormone-releasing hormone (LHRH) therapy, for adjuvant treatment in patients with hormone receptor-positive, HER2-negative early breast cancer at high risk of recurrence. The study also compares data from patients treated with abemaciclib plus endocrine therapy with or without LHRH, and those receiving endocrine monotherapy with or without LHRH. This observational study aims to understand treatment decisions and clinical use of ribociclib after its approval, collecting socio-economic data, quality of life, and patient compliance information. Participants receive treatment based on their physician's clinical judgment without study-assigned interventions. The treatments observed include ribociclib with an aromatase inhibitor LHRH, abemaciclib with endocrine therapy LHRH, or endocrine monotherapy LHRH. The study is conducted in various breast cancer centers and gynecological practices in Germany and Austria to represent local healthcare settings. Participants undergo assessments to monitor treatment effectiveness, safety, quality of life, and adherence to therapy over time. Data collected include clinical outcomes, adverse events, socio-economic status, and patient-reported compliance. The primary outcome measured is invasive disease-free survival over 36 months. This information will help inform clinical decision-making and improve outcomes for patients with early breast cancer in routine practice.

Researchers are investigating the effectiveness, safety, and tolerability of combining baxdrostat with dapagliflozin compared to dapagliflozin alone in people with chronic kidney disease (CKD) and high blood pressure. This Phase III, international, multicenter, double-blind, placebo-controlled study aims to see if this combination reduces risks such as significant kidney function decline, kidney failure, heart failure events, or cardiovascular death. The study includes a 4-week run-in period where participants not previously treated with SGLT2 inhibitors receive dapagliflozin alone. After this, participants are randomly assigned to receive either baxdrostat plus dapagliflozin or placebo plus dapagliflozin in a double-blinded manner. Study visits occur frequently initially (at 2, 4, 8, 16, 34, and 52 weeks after randomization) and then approximately every 4 months. If participants stop the blinded treatment early, they continue dapagliflozin alone unless specific criteria require its discontinuation. Participants will undergo regular assessments including blood pressure monitoring and laboratory tests related to kidney function and cardiovascular health. The primary outcome measures the reduction in risk of major kidney and heart events over up to 37 months. Even if participants stop the study treatment, they will continue follow-up visits and data collection to ensure comprehensive safety and efficacy evaluation throughout the study duration.

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 treatments for patients with high risk chronic lymphocytic leukemia (CLL), a common and aggressive form of leukemia. This phase 3, open-label, randomized study aims to compare a triple combination therapy of acalabrutinib, obinutuzumab, and venetoclax (GAVe) against a double combination of obinutuzumab and venetoclax (GVe) to see which better prolongs progression-free survival (PFS). High risk CLL patients are identified by specific genetic risk factors such as 17p-deletion, TP53-mutation, complex karyotype, or unmutated IGHV gene status, which indicate a poorer prognosis and less response to chemotherapy. Participants receive fixed-duration treatments. The triple combination group receives obinutuzumab via intravenous infusion during cycles 1 through 6, venetoclax orally with a gradual dose ramp-up from cycle 1 to 12, and acalabrutinib orally twice daily during cycles 15 to 24. The comparison group receives obinutuzumab and venetoclax on the same schedules but without acalabrutinib. The study investigates how adding the BTK inhibitor acalabrutinib to the existing combination may improve outcomes by targeting different pathways and reducing early disease progression. During the study, participants are closely monitored for progression-free survival over 50 months after the first patient is included. Researchers assess clinical status, laboratory tests, and genetic markers to evaluate response and safety. The study also tracks liver and kidney function, infection status, and adverse events to ensure treatment tolerability. The total duration includes initial treatment cycles and extended follow-up to measure the long-term effectiveness of these therapies in high risk CLL patients.

Researchers are conducting a global study to understand the impact of moderate to severe alopecia areata (AA), non-segmental vitiligo (NSV), and hidradenitis suppurativa (HS) on adolescents and adults. This study aims to assess the burden these conditions place on patients' quality of life and daily functioning in a large real-world population. The study involves participants diagnosed by a physician with one of the three conditions: AA, NSV, or HS. There are no interventional treatments or medications being tested in this study, as it is observational in nature. Data collection focuses on patient-reported outcomes and measures that evaluate disease severity and its effects. Participants will complete various questionnaires and assessments related to their condition, such as the Alopecia Areata Symptom Impact Scale (AASIS) for AA, the Severity of Alopecia Tool (SALT) for scalp hair loss in AA, the Facial Vitiligo Area Scoring Index (F-VASI) and Vitiligo Quality of Life Score (VitiQoL) for vitiligo, and the Dermatology Life Quality Index (DLQI) and International Hidradenitis Suppurativa Severity Scoring System (IHS4) for HS. These tools help researchers understand how symptoms affect quality of life and disease severity. The study collects information up to the day of the study visit.

Researchers are evaluating the safety and effectiveness of divarasib combined with pembrolizumab compared to pembrolizumab with pemetrexed and either carboplatin or cisplatin. The study focuses on adults with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) that has a specific KRAS G12C mutation. This is a Phase III trial aiming to improve first-line treatment options for these patients. Participants will receive one of two treatment combinations. One group will take divarasib orally once daily along with pembrolizumab given through an intravenous infusion every three weeks. The other group will receive pembrolizumab with pemetrexed and either carboplatin or cisplatin, all administered by intravenous infusion every three weeks. Treatment schedules and dosages are carefully monitored during the study. Throughout the study, participants will be regularly assessed for progression-free survival and overall survival, with follow-up lasting up to approximately five years. Researchers will perform various evaluations including tumor measurements and safety monitoring. This long-term observation helps to understand the treatments' effects and safety over time, supporting informed decisions for future lung cancer therapies.

Researchers are evaluating the effect of a triple therapy inhaler called BGF MDI containing budesonide, glycopyrronium, and formoterol fumarate compared with a dual therapy inhaler called GFF MDI containing glycopyrronium and formoterol fumarate in people with Chronic Obstructive Pulmonary Disease (COPD) who have a higher risk of heart and lung problems. This Phase III randomized, double-blind, parallel group study takes place at multiple centers and focuses on cardiopulmonary outcomes in these patients. Participants receive either the BGF MDI 320/14.4/9.6 micrograms twice daily or the GFF MDI 14.4/9.6 micrograms twice daily. The treatments are inhaled using metered dose inhalers. The study compares these two therapies over time to see how they affect the time until the first severe heart or lung event occurs. The study design ensures that neither participants nor researchers know which treatment is given to reduce bias. During the study, participants will have regular visits to the study site or virtual visits to complete assessments. Researchers will monitor lung function, symptoms, and blood tests, including blood eosinophil counts and COPD assessment test scores. The main outcome measured is the time to the first severe cardiac or COPD event, with follow-up lasting up to three years. Safety and adherence to treatment will also be closely observed throughout the study period.