Mannheim

Researchers are investigating CGT9486 bezuclastinib in a Phase 2 open-label study for adults with Advanced Systemic Mastocytosis AdvSM, including Aggressive Systemic Mastocytosis ASM, Systemic Mastocytosis with an Associated Hematologic Neoplasm SM-AHN, and Mast Cell Leukemia MCL. This study aims to evaluate the drugs safety, efficacy, pharmacokinetics, and pharmacodynamics in these conditions. Participants receive bezuclastinib tablets taken orally in continuous 28-day cycles. The study has two parts conducted over 18 months each Part I focuses on identifying active and tolerable doses, while Part II assesses treatment effectiveness by measuring the modified IWG Objective Response Rate ORR and confirms exposure-response relationships. During the study, participants will undergo evaluations including blood and bone marrow tests, imaging for spleen and liver size, and monitoring of mutation levels and serum tryptase. Researchers will track adverse events, duration and time to response, progression-free and overall survival. The total study duration includes these assessments over 18 months.

Researchers are studying the effects of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM who have symptoms not well controlled by current treatments. This randomized, double-blind, placebo-controlled Phase 23 trial includes participants with ISM and smoldering systemic mastocytosis SSM, aiming to evaluate both safety and efficacy of the treatments. The study is sponsored by Blueprint Medicines Corporation and includes participants who have previously used selective KIT inhibitors as well as pharmacokinetic groups. Participants will be assigned to receive either elenestinib or placebo along with symptom directed therapies tailored individually. Elenestinib is taken orally once daily. The study is organized into multiple parts Parts 1 and 2 involve treatment periods lasting up to approximately 48 weeks, after which participants in Part 2 may continue into Part 3 and receive open-label elenestinib for up to five years. Part K enrolls those previously treated with KIT inhibitors. Symptom directed therapy doses are stabilized before treatment and maintained throughout. During the trial, participants will be monitored regularly for side effects and symptom changes using the ISM-Symptom Assessment Form ISM-SAF and other measures such as serum tryptase levels, KIT D816V allele fraction, bone marrow mast cell counts, and quality of life assessments. Safety will be tracked through adverse event reporting. The study duration can extend up to five years, allowing long-term evaluation of treatment effects and symptom control. Participants will have ongoing evaluations at set intervals including baseline, weeks 13, 24, 48, and beyond as applicable.

Researchers are investigating treatments for oligodendrogliomas, a type of brain tumor classified by specific genetic markers including mutations in isocitrate dehydrogenase IDH and co-deletion of chromosomes 1p19q. This trial focuses on adults with newly diagnosed grade 2 or 3 gliomas, aiming to improve survival without loss of brain function, cognition, or quality of life. The study compares two treatment approaches to determine the best timing and combination of chemotherapy and radiotherapy. Participants are randomly assigned to receive either standard chemoradiation with procarbazine, CCNU lomustine, and vincristine PCV combined with radiotherapy, or an experimental approach starting with chemotherapy using lomustine and temozolomide CETEG followed by radiotherapy and PCV at tumor progression. Radiotherapy is delivered over about 5 to 6 weeks, with doses adjusted for tumor grade. Chemotherapy cycles last 6 weeks and include specified doses of oral and intravenous drugs. During the study, participants undergo regular magnetic resonance imaging MRI scans every three months, neurological assessments, quality of life questionnaires, and cognitive testing annually. The main outcome measured is qualified overall survival, which tracks survival without significant cognitive or functional decline. The study lasts up to 10 years, with ongoing monitoring of tumor progression, treatment response, and patient wellbeing. Safety and side effects are carefully assessed throughout the trial.

Researchers are evaluating the safety, blood levels, and antiviral effects of the antibody BNT351 in adults living with and without HIV. This Phase 1 clinical trial aims to understand how BNT351 behaves in the body and how it affects HIV levels in people living with HIV. It includes a first-in-human randomized, double-blind, placebo-controlled phase for people without HIV and an open-label proof-of-concept phase for people with HIV.

Researchers are evaluating the safety and effectiveness of trontinemab in people aged 50 to 90 years who have early symptomatic Alzheimers disease, ranging from mild cognitive impairment to mild dementia. The study is a phase III trial designed to compare trontinemab with a placebo to better understand its impact on cognitive decline in Alzheimers patients. Participants will be randomly assigned to receive either intravenous IV trontinemab or an IV placebo. The study is double-blind, meaning neither the participants nor the researchers know who receives the drug or placebo. Treatment and monitoring will continue for 72 weeks, during which various cognitive and biological measures will be assessed. Throughout the study, participants will undergo regular assessments including cognitive tests like the Clinical Dementia Rating, Sum of Boxes CDR-SB, and the Mini-Mental State Examination MMSE. Brain imaging scans such as amyloid and tau PET scans, as well as MRI, will be used to observe changes in brain pathology. Researchers will also monitor safety by tracking adverse events, infusion reactions, and the presence of antibodies against trontinemab. Participants will be supported by a study partner and will be closely followed during the entire study period.

Researchers are evaluating the effects of pelacarsen TQJ230, given as a monthly subcutaneous injection, on slowing the progression of calcific aortic valve stenosis in adults aged 50 to under 80 years with elevated Lipoproteina levels. This phase 2, randomized, double-blind, placebo-controlled multicenter trial aims to assess the efficacy, safety, and tolerability of pelacarsen compared to a matching placebo. The study is sponsored by Novartis Pharmaceuticals and focuses on patients with mild to moderate calcific aortic valve stenosis who are optimally treated for cardiovascular risk factors. Participants receive either pelacarsen 80 mg or a placebo via a prefilled syringe injected under the skin once every month. The study includes two groups one receiving the active drug and the other receiving a placebo, both administered in the same way. The trial will last up to 36 months, during which patients will be monitored for changes in aortic valve function and calcium levels. Throughout the study, participants will undergo evaluations including measurement of peak aortic jet velocity and aortic valve calcium scores at 36 months. Additional assessments include changes in Lipoproteina levels at 12 months and monitoring of fibrocalcific thickening of the valve and clinical events over the course of the trial. Safety will be closely monitored to ensure participants well-being during the entire study period.

This research aims to observe patients with relapsing multiple sclerosis RMS who are being treated with approved injectable or selected oral disease-modifying therapies DMTs in Germany. The study collects data to understand how these treatments are used in routine care and their effects over time. It is an observational, non-interventional, multicenter, open-label study sponsored by Novartis Pharmaceuticals. Patients will be followed in two cohorts Cohort 1 includes patients starting or recently started on injectable DMTs, and Cohort 2 includes patients starting or recently started on either ofatumumab or other approved injectable or oral DMTs. The core observational period is up to two years, with an optional extension adding another two years, totaling up to about four years of observation. Treatment decisions are made independently by patients and their physicians, and no study-mandated treatment or monitoring is imposed. Participants will provide data through questionnaires and electronic case report forms, with medical history including disease duration, lab values, MRI results, and relapse information collected. Routine clinical care assessments and telemedicine visits may occur at the investigators discretion. The study measures include treatment continuation rates, disability scores, relapse rates, quality of life, fatigue, anxiety, depression, MRI lesion monitoring, and safety events, with follow-up visits scheduled as per standard care over the study period.

Researchers are conducting a prospective, multicenter, observational study in Germany to evaluate the clinical value and impact of serum neurofilament light sNfL as a prognostic marker for disease activity in patients with relapsing Multiple Sclerosis MS. The study focuses on patients who have received category 1 disease-modifying therapies DMTs and monitors routinely assessed sNfL values to better understand their role in patient management. Participants in the study either continue their current category 1 DMT treatment or switch to ofatumumab based on their physicians clinical judgment, independent of study enrollment. Category 1 DMTs include medications such as dimethylfumarate, diroximelfumarate, glatiramer acetate, interferon beta, and teriflunomide. Data will be collected over a maximum period of 24 months during routine clinical visits, with no specific protocol dictating observation frequency or diagnostic procedures. During the study, researchers will gather primary data including sNfL test results and track various outcomes like disease activity, treatment adherence, patient-reported fatigue, quality of life, and treatment satisfaction. Assessments will align with standard care practices and guidelines, and the study will measure outcomes at baseline, 12 months, and 24 months. The study aims to provide insights into the use of sNfL in clinical practice and its implications for managing relapsing MS.

Researchers are studying the real-world effectiveness, safety, and patient experience 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 patient compliance and quality of life among those treated with ribociclib, abemaciclib with endocrine therapy, or endocrine therapy alone. The goal is to understand treatment decisions and how these therapies perform in routine care settings. Participants receive treatment as prescribed by their doctors based on local guidelines and product information for ribociclib plus aromatase inhibitor with or without LHRH, abemaciclib with endocrine therapy plus or minus LHRH, or endocrine therapy alone plus or minus LHRH. There is no random treatment assignment since this is an observational study. Baseline data are collected shortly before or after treatment initiation depending on the cohort. During the study, patients will be followed for up to 36 months to monitor invasive disease-free survival and other health outcomes. Researchers will collect information on adverse events, treatment modifications, adherence measures, quality of life questionnaires, and socio-economic factors at various timepoints. This will provide insights into treatment tolerability, patient compliance, and overall impact on quality of life in a real-world setting.

Researchers are evaluating the safety, tolerability, how the body processes pharmacokinetics, how the body responds pharmacodynamics, and effectiveness of TERN-701, a selective inhibitor targeting BCR-ABL1, in adults with chronic phase chronic myeloid leukemia who have received prior treatment. This Phase 12 trial focuses on participants with treatment challenges such as resistance or intolerance to previous therapies. The study is sponsored by Terns, Inc. and aims to better understand TERN-701s impact in this patient group. The trial has two main parts. Part 1 involves dose escalation where participants receive increasing doses of TERN-701 once daily to determine safe and effective dose levels. Part 2 includes randomized dose expansion cohorts to further assess safety and efficacy at two selected doses from Part 1, and an additional mutation cohort Part 2m evaluating a specific 500 mg dose in participants with certain resistance mutations. Treatment is given continuously in 28-day cycles with scheduled clinic visits at specified days during the first cycle and then on Day 1 of subsequent cycles. Participants will be closely monitored through regular visits for safety, tolerability, and response to treatment. Researchers will evaluate dose-limiting toxicities, adverse events, hematologic and molecular responses, and changes in BCR-ABL1 transcript levels over up to three years. Approximately 180 participants are expected to enroll, contributing to comprehensive data collection on TERN-701s performance and safety in this chronic leukemia population.