Cp 44630 Guadalajara Jalisco, Mexico

NB02 (Poseltinib) Combined Rituximab and Lenalidomide in R/R PCNSL

For outpatients or inpatients who meet the criteria for subject selection, the study is conducted with patients who have given a sufficient explanation of the study and who voluntarily consented to participate in the study. Patients enrolled in the study receive a combination therapy of NB02, Rituximab and lenalidomide according to the criteria specified in the protocol. Induction(R2P) 21 days per cycles, 6 cycles - NB02 : 60mg BID PO, Day 1-21 - Rituximab 375mg/m2 DAY IV Day 1, 8, 15 at 1st cycle; D1 at 2nd to 6th cycles - Lenalidomide : 20mg QD PO, Day 1-14 Maintenance(RP) 21 days per cycles, until Progression - NB02 : 60mg BID PO, Day 1-21 - Lenalidomide : 20mg QD PO, Day 1-14

A Study of Belantamab Mafodotin Administered in Combination With Lenalidomide and Dexamethasone (BRd) Versus Daratumumab, Lenalidomide, and Dexamethasone (DRd) in Participants With Newly Diagnosed Multiple Myeloma (NDMM) Who Are Ineligible for Autologous Stem Cell Transplantation (TI-NDMM)

Efficacy and Safety of SP-8203 (Otaplimastat) in Patients With Acute Ischemic Stroke Receiving Thrombolytic Standard of Care

Intravenous administration of SP-8203 (otaplimastat), a multipotent neuroprotectant inhibiting matrix metalloprotease activity, significantly reduced infarct volume and recombinant tissue plasminogen activator (rtPA)/ ischemic-induced damage in animal models. This clinical study is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 (otaplimastat) and thrombolytic standard of care in acute ischemic stroke patient. As a standard of care, thrombolytic therapy (for instance, recombinant tissue plasminogen activator) will be administered. When reperfusion is not achieved in spite of thrombolytic therapy, endovascular therapy can be performed. A total of 852 participants will be enrolled in double-blind, randomized and parallel design with 426 participants assigned to 80 mg/day SP-8203 arm or placebo arm, respectively. Eligible participants are the patients with neurologic deficit of ≥8 point on National Institute of Health Stroke Scale (NIHSS) score. The participant will receive the study intervention a total of 6 times, with 12 hours intervals. Imaging test will be performed using validated machine and method. The participant will have initial brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) performed within 6 hours before or after the administration of study intervention, and brain Computed Tomography (CT) will be performed at 24±3 hours after completion of the first administration of study intervention. Brain Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) will be followed-up on Day 5, and additionally the participant will undergo additional functional and neurological evaluations for up to 90 days. When unexpected serious adverse reaction occurs during the clinical study, Data Safety Monitoring Board (DSMB) will be convened to validation safety.

A Study to Investigate the Effect on Lung Function of an Approved COPD Treatment (BGF, With HFA Propellant) Compared to BGF Formulated With a New Propellant (HFO) in Participants 40 to 80 Years of Age With COPD

This is a phase III, randomised, placebo-controlled, double-blind, multi-centre, 4-week, 3-way crossover pharmacodynamic study to assess the equivalence of BGF MDI HFO compared with BGF MDI HFA in participants with COPD. To demonstrate assay sensitivity, BGF MDI HFA will be compared to placebo MDI HFA for superiority in lung function, both pre- and post-dose. Eligible participants are between 40 and 80 years of age, inclusive, who have an established clinical history of COPD as defined by the ATS/ERS. Participants are required to have an FEV1/FVC ratio of < 0.70, have a post-bronchodilator FEV1 ≥ 40% and < 80% predicted normal value, have a blood eosinophil count < 300 cells/μL, and be current or former cigarette smokers with a history of at least 10 pack-years. Participants must not have had a COPD exacerbation treated with oral corticosteroids or antibiotics within 4 months prior to initiation of screening, and must not have had a COPD exacerbation that required hospitalisation within 12 months prior to initiation of screening. Eligible participants are those on treatment with LABA, LAMA, LAMA/LABA (open or fixed-dose combination), ICS/LABA (open or fixed-dose combination) inhaled maintenance therapies, or SABA, SAMA, or SAMA/SABA scheduled or as-needed inhaled therapies, or who are naïve to COPD therapy. This study will be conducted at approximately 95 sites globally. After screening, participants will be randomised 1:1:1:1:1:1 to receive study interventions in one of 6 possible treatment sequences.

Arterial Wall Shear Stress After Intracranial Artery Recanalization

1. Background The prognosis for ischemic stroke patients experiencing acute major intracranial artery occlusion is determined by a variety of factors. The status of arterial recanalization and the time taken to achieve recanalization play pivotal roles in determining patient outcomes. Even under similar conditions, short or long-term outcomes significantly differ among patients, making it challenging to solely explain with traditional risk factors. An acute occlusion in a major intracranial artery results in significant alterations in cerebral blood flow, enhancing flow through the Circle of Willis and collateral circulation to make up for the reduced blood supply to the affected area. After thrombectomy, the patterns of intracranial blood flow. changes again. Wall Shear Stress (WSS) is the frictional resistance force exerted by blood flow as it directly interacts with the vascular walls, and it serves as a critical indicator of vascular health. WSS is well-known for its correlation with atherosclerotic changes. Studies have shown that WSS in the internal carotid artery of ischemic stroke patients is lower compared to healthy individuals. Additionally, WSS was found to be reduced in the carotid artery of patients with lacunar infarctions. WSS in large artery strokes was lower than in the cardioembolic group. There have also been reports linking WSS to the progression of Moyamoya disease, suggesting that WSS may be associated with various vascular pathophysiologies, not just atherosclerotic changes. Time-of-Flight Magnetic Resonance Angiography (TOF-MRA) is a commonly used brain MRI technique, often utilized in conjunction with CT angiography to assess the course and condition of intracranial arteries. The signal intensity from MRA-TOF presents diverse distributions across different subjects and arteries. Based on this, the concept of Signal Intensity Gradient (SIG) has been derived. SIG has shown a strong correlation (correlation coefficient >0.8) with Computational Fluid Dynamics (CFD), a well-known method for assessing blood shear stress. In patients with the large artery atherosclerosis subtype of stroke, the SIG in the ipsilateral internal carotid artery was significantly lower than that on the contralateral side. These findings suggest a potential association between SIG, vascular shear stress, and the related pathophysiology. There is no need for additional imaging beyond TOF, and it is possible to measure even arteries of relatively small diameter. Therefore, SIG enables the analysis of shear stress pattern in major cerebral arteries before and after recanalization. 2. Aims We aim to investigate the blood flow patterns and characteristics in the periods of pre and post-recanalization using SIG. 3. Target number of participants A total of 160 participants (20 individuals from each center, total 8 centers) 4. Sample size assessment Although there haven't been many similar studies in the past, a study (PLoS One. 2020 Sep 21;15(9):e0238620) conducted a hemodynamic evaluation before and after major vessel recanalization, analyzing 11 patients. Sample size estimation using G*Power indicated that registration of approximately 144 patients would be necessary. Taking into account factors such as image quality, we anticipate an additional recruitment of about 10%, resulting in a final target of 160 cases. 5. Data Acquisition This study is a retrospective cohort study that involves the collection of electronic medical records and imaging data. Imaging Data to be Collected: (All images will be collected as DICOM files) - Brain MRI (Specific imaging conditions: Fluid Attenuated Inversion Recovery, Susceptibility Weighted Imaging, T1-Weighted Imaging, T2-Weighted Imaging, Diffusion Weighted Imaging, Apparent Diffusion Coefficient) - Brain MRA (Specific imaging conditions: source images from both extra and intracranial TOF-MRA, and 3D TOF-MRA) 6. Derivation of Intravascular Shear Stress (SIG) Through Image Analysis The transferred DICOM files are reconstructed into 3D vasculature using a separate software (VINT). SIG values for the major arterial segments within the cranial cavity are extracted. The major arterial segments are as follows, and the points where laminar flow of blood is formed were selected, considering the characteristics of the SIG technique: - Internal Carotid Artery: C1 distal segment prior to the horizontal intrapetrous segment - Vertebral Artery: V4 distal segment just before the formation of the basilar artery - Basilar Artery: mid to distal segment - Middle and Anterior Cerebral Arteries: proximal 1/2 or 1/3 segment - Posterior Cerebral Artery: P2 segment distal to the posterior communicating artery The measurements can be calculated into various SIG values (average, maximum, minimum, deviation). 7. Statistical Analysis Each patient will be classified into two groups based on their blood flow characteristics before and after recanalization. In a preliminary study, two types of blood flow (shear stress) changes were observed. Firstly, there was a pattern in which, following cerebral vascular occlusion, blood flow to the ischemic area was provided, and upon recanalization, it returned to the typical blood flow pattern. Secondly, there was a case where the overall blood flow in the major cerebral vessels increased after recanalization. To analyze these patterns, Paired t-test and Wilcoxon Signed-Rank Test will be used. (While this study is expected to proceed in the same manner as the group classification in the preliminary study, the classification method may be revised as the research progresses.) For comparing mean values between groups, Independent Samples t-Test and Mann-Whitney U Test will be utilized. Categorical variables will be analyzed using the Chi-square Test or Fisher's Exact Test. Variables such as mRS (modified Rankin Scale), which are ordinal, will be assessed using the Mann-Whitney U Test or Wilcoxon Rank-Sum Test to utilize the median values.

A Study to Compare the Pharmacokinetics, Efficacy, Safety, and Immunogenicity of Pembrolizumab (SB27, EU Sourced Keytruda, and US Sourced Keytruda) in Subjects with Stage II-IIIA NSCLC Following Complete Resection and Adjuvant Platinum-based Chemotherapy

FFR Versus IVUS with Angiography-Derived FFR for Clinical Outcomes in Patients with Coronary Artery Disease

1. Hypothesis: The IVUS-guided stent implantation after angiography-derived FFR-based decision-making will show superiority in terms of a lower rate of patients-oriented composite outcomes (POCO) at 24 months after randomization compared with the FFR-guided PCI strategy in patients with coronary stenosis. 2. Research materials and indication for revascularization: 2.1 Experimental group: PCI will be performed if angiography-derived FFR ≤0.80 and will be deferred if angiography-derived FFR >0.80; If PCI is performed, PCI optimization using IVUS will be performed following the recommended criteria: ① Plaque burden at stent edge ≤55%; ② Minimal stent area ≥ 5.5 mm2, or minimal stent area ≥ distal reference lumen area. 2.2 Control group: PCI will be performed if FFR ≤0.80 and will be deferred if FFR >0.80; If PCI is performed, PCI optimization using FFR will be performed following the recommended criteria: ① Post-PCI FFR ≥ 0.88, or ② Post-PCI ΔFFR ([FFR at stent distal edge] - [FFR at stent proximal edge]) < 0.05. 3. Sample size: In the post-hoc analysis of the FLAVOUR I study applying QFR analysis, the 2-year POCO rate was 13.0% in the PCI group with FFR ≤0.80 and undergoing FFR-based PCI optimization and 7.1% in the PCI group with QFR ≤0.80 and undergoing IVUS-based PCI optimization. Meanwhile, the 2-year POCO rate was 5.8% and 6.5% in the deferral of PCI group with FFR >0.80 and QFR >0.80, respectively. Assuming a PCI rate of 70% in patients with coronary artery lesions with 50-90% stenosis that is the inclusion criteria for the current study, and considering event rates from historical studies evaluating FFR- and QFR-guided PCI strategies, the cumulative incidence rate of POCO at 24 months was estimated to be 13.0% in the control group (FFR group) and 9.0% in the experimental group (QFR-IVUS group). - Primary endpoint: POCO, defined as a composite of death from any cause, MI, or any revascularization at 24 months after randomization. - Design: superiority - Sampling ratio: experimental group : control group = 1:1 - Type I error (α): One-sided 2.5% - Accrual time: 24 months - Total time: 4 years (accrual 24 months + follow-up 24 months) - Assumption: POCO 13.0% vs. 9.0% in control or experimental group, respectively - Statistical power (1- β): 90% - Primary statistical method: Kaplan-Meier survival analysis with log-rank test - Estimated attrition rate: total 10% - Stratification in randomization: Presence of diabetes mellitus Based on the above assumption, we would need total 1,942 patients (971 patients in each group) with consideration of an attrition rate.

A Trial to Learn How Effective and Safe Odronextamab is Compared to Standard of Care for Adult Participants With Previously Treated Aggressive B-cell Non-Hodgkin Lymphoma

A Trial to Learn How the Combination of Fianlimab With Cemiplimab and Chemotherapy Works Compared With Cemiplimab and Chemotherapy for Treating Adult Patients With Advanced Non-small Cell Lung Cancer

Clinical Impact of Intravascular Ultrasound-Based Artificial Intelligence Technologies (INNOVATE-PCI)

The aim of the study is to evaluate the performances and prognostic impact of coronary angiography & IVUS-based algorithms for decision making and stent optimization in a multicenter, prospective cohort. Between January 2020 and June 2025, a total of 3,000 patients who performed coronary angiography (± FFR) and have at least one coronary stenosis requiring PCI (as culprit) will be enrolled from 15 centers in South Korea. In addition, the deferred lesions with visual estimated diameter stenosis of >30% will be evaluated as non-culprits. Brief study design is as depicted in the following figure. Supervised ML algorithms include: 1) angiography- and IVUS-based algorithms for predicting FFR, 2) IVUS-based algorithm for plaque characterization, 3) IVUS-based algorithm for predicting stent expansion, and 4) post-stenting IVUS-based algorithm for predicting stent failure. In the prospective cohort, the performance of each model will be assessed. This registry trial composed of the treated (culprit) and the deferred (nonculprit) coronary lesions has two primary objectives as follow; 1) Primary objectives in treated (culprit) lesions is to see the impact of the integrated ML model on the development of culprit-related 2-year target vessel failure (TVF). 2) Primary objectives in deferred (nonculprit) lesions is to see the impact of the integrated ML model on the development of nonculprit-related 2-year TVF.