Bochum

Participants eligible for this trial will be randomized 1:1 into one of the two arms (Arm A and Arm B) stratified by: I) -Previous anti-angiogenic therapy (yes vs. no), II) BRAF/RAS mutation status (wildtype vs. mutation) or III) History of liver metastases (never vs. prior but treated). Patients in Arm A (experimental arm) will receive Fruquintinib (orally, 5 mg once a day, at day 1-21 of each 28-day cycle \[Q4W\]) plus Tislelizumab (i.v., 400 mg, at day 1 of each 42-day cycle \[Q6W\]). Patients in Arm B (control arm) will receive Trifluridine/tipiracil (orally, 35 mg/m2 twice a day, day 1-5 and day 8-12 of each 28-day cycle \[Q4W\]) plus Bevacizumab (i.v., 5 mg/kg, at day 1 of each 14-day cycle \[Q2W\]). The treatment will be performed until disease progression, unacceptable toxicity, patients' request, or end of protocol-defined treatment time (maximum of 15 months). All patients will be followed up for a maximum of 18 months after last patient in or until death, withdrawal of consent or loss to follow-up, whatever occurs first.

PERIODS is a prospective, phase IV, multi-centre, randomized, double-blind and placebo-controlled clinical trial that will investigate the effects of tirzepatide compared with placebo on ovarian dysfunction in premeno-pausal, overweight (BMI ≥ 27 kg/m2) women with PCOS. The primary endpoint is the improvement of ovarian dysfunction as defined by menstrual irregularity and ovulation frequency in overweight or obesity-related PCOS. All subjects will undergo a screening visit and a 72-week treatment period including a 20-week dose escalation up to the maximum tolerated dose. Lower doses of tirzepatide are permitted if intolerable side effects occur. However, even if a lower dose of tirzepatide turns out to be the maximum tolerated dose, this lower dose will be administered for the entire 20-week dose escalation period, followed by the 52-week maintenance dose. The safety follow-up period will be 4 weeks (for subjects completing or discontinuing IMP during the first 72 weeks). Long-term follow-up will be one year after discontinuation of IMP. The trial design is multi-centred with a planned number of 5 participating trial sites in Germany.

The primary objective of the NOA-18/IMPROVE CODEL trial is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event with respect to a sustained qOS is then defined as a functional and/or cognitive deterioration on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with 3-monthly MRI, assessment of the NANO (Neurologic assessment in neuro-oncology) scale, HRQoL, and KPS (Karnofsky performance status) and annually cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at 21 NOA (Neurooncology Working Party of the German Cancer Society) study sites in Germany.

This is a global, multicenter, prospective, observational registry of patients with Pompe disease, including those with late-onset pompe disease (LOPD) and infantile-onset pompe disease (IOPD). Both untreated patients and those being treated with an approved therapy for Pompe disease are eligible to participate. The objectives of the registry are: * To evaluate the long-term safety of Pompe disease treatments through collection of data that describe the frequency of adverse events (AEs)/serious adverse events (SAEs) occurring in Pompe disease patients * To evaluate the long-term real-world effectiveness of Pompe disease treatments * To evaluate the long-term real-world impact of Pompe disease treatments on quality of life (QOL) and patient-reported outcomes (PROs) * To describe the natural history of untreated Pompe disease

The prerequisite for participation in this observational study is the independent decision of the treating physician and patient to start an approved injectable or oral DMT for RMS as routine medical treatment. This decision must have been made prior to enrollment in this study. Cohort 1: The prospective observational period per patient in the core part will be up to approx. two years from the time of consent (2 years +2 months visit window). If a patient re-consents to the extension part, then the prospective extension observational period will be additional approx. two years, resulting in a total observational period (prospectively for the core and extension part \& retrospectively for the potential gap between core and extension part) of approx. 4 years (+ 2 month visit window). Cohort 2: The prospective observational period per patient will be up to approx. two years from the time of consent (2 years + 2 months visit window). The observational period will not be dictated by the protocol. The follow-up documentation will take place at a frequency defined as per investigator's discretion. The diagnostic or monitoring procedures are only those ordinarily applied to the therapeutic strategy and to routine clinical care, can be performed as telemedicine visits and will take place as per investigator's discretion.

Prospective, primary data will be collected from patients with sNfL outcomes in the context of switching to ofatumumab or continuing their current therapy. Data collection will cover a maximum period of 24 months. The observational period will not be dictated by the protocol. Baseline and follow-up visits will take place at a frequency defined as per Investigator´s discretion following clinical routine. The diagnostic or monitoring procedures are only those ordinarily applied to therapeutic strategy and routine clinical care. During the observation phase of the study, data will be collected according to standard of care as recommended by KKNMS (Competence Network Multiple Sclerosis in Germany). Eligible participants for the study are patients who have received treatment with category 1 DMTs and those who have included sNfL into their treatment decision-making process. These patients have the option to either continue their current DMT or switch to ofatumumab. According to local treatment guidelines, DMT category 1 include dimethylfumarate/diroximelfumarate, glatirameroids, Interferon beta and teriflunomide. The decision to switch to ofatumumab or to continue the current DMT category 1 therapy must be made by the treating physician independently of the decision to enroll the patient in the study.

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an aromatase inhibitor (AI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the current effective local summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the current effective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + AI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + AI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and Austrian breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + AI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

This is a non-interventional, prospective, post authorization safety study. Patients with gMG who are expected to start treatment with efgartigimod at enrolment or are within their first cycle of efgartigimod at enrolment will be eligible to enroll into the efgartigimod cohort. Patients with gMG who have not been exposed to efgartigimod and for whom it is not planned to start treatment with efgartigimod at enrolment will be eligible to enroll into the non-efgartigimod cohort.

The total duration of the study is 76 weeks and consists of: Screening (up to 4 weeks), Treatment Period 1 (16 weeks, double-blind treatment with remibrutinib (Dose A or Dose B) or placebo, Treatment Period 2 (52 weeks, treatment with remibrutinib (Dose A or Dose B) and Safety Follow-Up (treatment-free follow-up for 4 weeks). Participants who prematurely discontinue study treatment (either during Treatment Period 1 or Treatment Period 2) are encouraged to remain in the study. Participants who do not wish to remain in the study will enter a 4-week Safety Follow-Up period.

Patients will receive up to 15 doses of RO7198457 over the course of trial treatment.