Burgstetten, Germany

A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 in Adult Participants With Systemic Lupus Erythematosus or Idiopathic Inflammatory Myopathies.

This is an open-label, multi-centre Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD5492 in adult participants with either SLE or IIM. Participants will be enrolled in approximately 20 sites in 8 countries. The study consists of 2 parts: Part 1 - Single ascending dose (SAD) Part 1 will be a sequential SAD design in adult participants with SLE. Up to 5 dose levels of AZD5492 are planned to be investigated. Depending on emerging data, up to 4 additional dose levels may be added at the discretion of the Sponsor. The decision to open Part 2 will be made by the Safety Review Committee (SRC) based on the evaluation of all available data including safety, tolerability, PK, and PD from Part 1, and the dose levels and dosing strategy for Part 2 will be confirmed. After a screening period of up to 42 days, participants will receive 1 dose of AZD5492 and be followed up for at least 179 days post-dose. Part 2 - Step-up dosing (SUD) Part 2 will be a SUD design in adult participants with SLE, who previously did not participate in Part 1, and in adult participants with IIM. In Part 2, participants will receive 2 dose administrations, where the second dose will be administered 7 days after the first dose. The first (priming) dose of the step-up regimen will be agreed by the SRC. The second (target) dose will be escalated, and a minimum of 3 target dose levels are planned to be investigated in Part 2.

Bemarituzumab in FGFR2b+ Patients with Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction, Who Failed At Least One Prior Line of Palliative Chemotherapy

A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

During the screening period study eligibility will be assessed and the participants' individual LDL-C target according to guideline (Mach et al., 2020) will be determined. Among other criteria, at screening, a participant must be on a stable maximally tolerated dose of a HI statin with either atorvastatin ≥40 mg once a day (QD) or rosuvastatin ≥20 mg QD (+/- Ezetimibe [10mg]) for ≥ 4 weeks with which, however, a target LDL-C of < 70 mg/dL is not reached. During the open-label treatment period, all participants, who fulfill the inclusion/exclusion criteria, will be randomized at V1 (Day 1) in a 1:1 open-label fashion to either Inclisiran sodium 300 mg s.c. (administered at Day 1 and Day 90) or to BPA tablets 180 mg p.o. (given once daily). Participants will be required to maintain their background lipid-lowering treatment (maximally tolerated statin dose +/- Ezetimibe) unchanged for the duration of the study. The end of treatment (EOT) is reached at day 150. A Safety-Follow-up call will be conducted 30 days after EOT visit (Day 180). The overall study duration is approximately 190 days but can vary depending on individual screening and the visit windows allowed for the treatment period and EOS visit.

A Study in Patients With Moderate to Severe Plaque Psoriasis to Evaluate the Efficacy and Safety of ESK-001

Real-world Experience With Lutetium Vipivotide Tetraxetan in Metastatic Castration Resistant Prostate Cancer

This non-interventional observational, prospective cohort study is using primary data collection to describe the routine clinical practice and HRQoL of patients with Metastatic castration-resistant prostate cancer (mCRPC) initiating lutetium (177Lu) vipivotide tetraxetan using patient questionnaires. Data will be collected at the following time points: pre-index (if patient is eligible), index date (first application of lutetium (177Lu) vipivotide tetraxetan), during treatment, at EoT, and during follow-up. The duration of a treatment cycle is 6 weeks (± 1 week). Patients will be treated for up to 6 cycles (as per local label). EoT visit / assessments will be performed after the last lutetium (177Lu) vipivotide tetraxetan application. Follow-up period: patient data will be collected if available up to 1 year after EoT.

Real World Use of Tocilizumab Biosimilar studY

Iberdomide Vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myeloma

Prospective, multicentre, randomised, parallel group, open, phase III clinical trial for a maintenance therapy, for patients who underwent an induction therapy and autologous stem cell transplantation in the GMMG-HD8/DSMM XIX trial. Investigational Medicinal Product: Iberdomid (oral), isatuximab (subcutaneous administration via a wearable injector system). Randomisation will be performed centrally by GMMG/DSMM offices after verification of the eligibility of the patient. At the time of study inclusion, randomization will be performed into arm A (iberdomide) or arm B (iberdomide + isatuximab). Randomization will be stratified by centrally assessed MRD negativity status (yes vs. no vs. unknown); assessed by NGF from BMA; sensitivity of 10^-5; independent of standard IMWG response) and number of HDM/ASCT (single vs. tandem). Patients randomized in arm A will receive 39 cycles of the drug iberdomide, a Cereblon E3 Ubiquitin Ligase Modulating Drug (CELMoD®) that shares structural similarities to the immunomodulatory compounds (IMiDs) such as thalidomide and lenalidomide. Each cycle will last for 29 days. Patients in arm B will receive the same the 39 cycles of iberdomide plus monoclonal anti-CD38 antibody isatuximab subcutaneously. In both arms, patients will receive 20 mg dexamethasone in cycle 1, on the same days as the isatuximab administration in Arm B. End of study will be after 36 months of the maintenance therapy. There is one primary objective: - Demonstration of superiority of iberdomide plus isatuximab compared to iberdomide with respect to bone marrow minimal residual disease (MRD) negativity rates (sensitivity 2x10^-6 via next-generation flow cytometry [NGF]) after two years of maintenance therapy. There is one key secondary objective: - PFS, defined as time from randomization to disease progression or death from any cause, whichever occurs first. Further secondary objectives are: - Rates of sustained MRD negativity (at sensitivity levels of 10-5 and 2x10^-6 via NGF from BMA) after 1, 2 and 3 years of maintenance therapy. - Conversion from MRD positive to negative (at sensitivity levels of 10^-5 and 2x10^-6 via NGF from BMA). - Rates of best overall response to treatment (BOR). - Rates of partial response (PR), very good partial response (VGPR), complete response (CR) and stringent complete response (sCR). - Time-to-next-treatment (TTNT). - PFS on subsequent line of therapy. - Overall survival (OS). - Improvement of IMWG response categories (PR, VGPR, CR, sCR). - Proportions of patients in both treatment arms maintaining BOR and CR from baseline. - Assessment of quality-of-life (QoL) via the EORTC-QLQC30, EORTC-QLQMY20, and EQ-5D-5L questionnaires.

Safety and Tolerability of a Timolol Releasing Intraocular Implant in Subjects With Primary Open-angle Glaucoma

Timolol will be delivered through an investigational drug called 'TimoD implant'. This implant is placed inside one eye, the study eye, with the help of an instrument (investigational device) called an injector system. Three dose ranges of TimoD implant will be tested (low, intermediate, and high) in 3 groups of 6 participants. The Timolol will be released slowly through the implant for up to 1 year (main phase). Approximately 1 year after the TimoD implant is placed into the eye and in absence of contraindications, the participants will be invited to continue the study in an extension phase. If the participants agree to enter the extension phase and the study investigator confirms it is safe for them, the TimoD implant will remain in the study eye for one additional year.

Recovery From Acute Immune Failure in Septic Shock by Immune Cell Extracorporeal Therapy - Observational Long-term Outcome Follow up

Sepsis is a worldwide health threat because of high mortality and the development of long-lasting disabilities, including physical and cognitive impairment and mental disorders, known collectively as post-intensive care syndrome (PICS), which contribute to reduced health-related quality of life (HRQoL) for several years even after successful recovery from the initial acute sepsis state. Sepsis survivors often need a longer period of rehabilitation, consuming more medical and social resources and struggle with financial burdens. In the ReActIF-ICE study, that started enrolling patients in July 2022, up to 142 subjects with severe sepsis are to be enrolled and randomized into a therapy group (receiving the ARTICE treatment (extracorporeal immune cell plasma perfusion) on top of standard care) and control group (standard care only). These subjects were followed up according the ReActIF-ICE study protocol for 90 days. Since there is still a large need for long-term outcome data of sepsis patients, collecting data of the ReActIF-ICE patients over a longer period of time would provide important additional information regarding: 1. General long term clinical and socio-economic outcome of sepsis survivors 2. Long-term outcome details of the ReActIF-ICE patient population 3. The potential long-term medical outcome effects of the additional ARTICE treatment compared to standard treatment alone. 4. The potential long-term health-related quality-of-life effects of ReActIF-ICE patient population 5. The potential long-term health-related quality-of-life effects of the additional ARTICE treatment compared to standard treatment alone. In this long term follow up study, the enrolled subjects shall be followed up beyond 90 days for up to 5 years.

MB-CART19.1 in Refractory SLE

Patients will be treated in cohorts of 3. After each cohort, the Safety Monitoring Board (SMB) will meet to assess whether the next higher dose level can be opened. The follow-up of the patients will be performed in 3 steps: - Until day 28 after treatment, the patients will be followed up closely by monitoring vital functions and lab parameters for signs of AEs and DLTs. Blood samples for the determination of persistence and phenotype of infused CAR+ cells will be taken. B cell aplasia in peripheral blood will be determined together with other secondary and exploratory biomarkers, response will be assessed and AEs will be documented. - In the second follow-up phase until 1 year, blood samples for the determination of persistence and phenotype of infused CAR+ cells will be taken, B cell aplasia will be determined, response will be assessed and AEs will be documented until end of week 12, afterwards serious AEs (SAE) and AEs of special interest (AESI) will be documented, serious adverse reactions (SAR)/AESI will be reported. - All patients irrespective of the clinical response will be followed up then for 1 more year or until the patient is lost to follow-up or has died. After completion of this last follow-up phase, patients will be rolled over to a subsequent follow-up observation for up to further 13 years.