Nyireghaza, Hungary
Rhu-pGSN for Acute Respiratory Distress Syndrome (ARDS)
Potential subjects hospitalized with pneumonia or other infections are to be screened within 24 hours of diagnosis of ARDS. The Sponsor aims to identify as early as possible patients in the hospital who have developed acute hypoxemic respiratory failure within 7 days of the precipitating infection (often fever, rigors, chills, increased heart rate, increased respiratory rate, pain, cough, etc.) leading to ARDS resulting in mechanical or noninvasive ventilation or high-flow nasal oxygen (HFNO) supplementation with ≥50% O2 at a flow rate of ≥30 L/min. Patients who do not qualify for the study at the initial screening visit because of mild ARDS may subsequently progress to moderate-to-severe ARDS and should be reassessed at least daily for the 7 days following the precipitating infection. Once informed consent is obtained, the following assessments/procedures will be performed: 1. Confirm the potential participant has acute hypoxemic respiratory failure qualifying as moderate-to-severe ARDS for ≤48 hours following a suspected or confirmed infection within the preceding week. Moderate-to-severe ARDS is defined by the calculated or estimated ratio of arterial pressure of O2 to the fraction of inspired O2 [P/F ratio] ≤150. The P/F ratio will be computed from the most recent arterial blood gas obtained no more than 12 hours earlier than randomization. For potential subjects on high-flow nasal oxygen with ≥50% O2 at a flow rate of ≥30 L/min, the P/F ratio will be estimated assuming 50% delivered O2. If eligible and entered in the trial, the following steps should be taken. 2. Record medical history, including concomitant medications and current clinical status. Specify the site and etiology (if known) of infection, indicating if the lung ("direct ARDS") or another organ ("indirect ARDS") is the primary site of infection. 3. Perform pregnancy test (urine or blood) for women of childbearing potential if not already performed during the current hospitalization. 4. Collect pretreatment blood samples for measurement of baseline pGSN and analysis of antibodies against pGSN. 5. Perform physical examination and document results of the chest x-ray (CXR) and/or computed tomography (CT) scan, if CXR is inadequate if not already available as per SOC. 6. Obtain blood and sputum cultures and electrocardiogram (EKG) per SOC (if not already performed). Document the site of infection by collecting specimens as indicated: sputum (bacterial, viral, and mycobacterial, as indicated) and blood cultures, sputum Gram-stains, antigen detection on respiratory and urine specimens, and syndromic nucleic acid amplification tests (NAATs) on respiratory specimens (including a viral and other respiratory pathogen polymerase chain reaction [PCR] panel), where possible. Other specimens from possible sites of infection (e.g., urine, intra-abdominal drainage, skin or soft-tissue abscesses) should be cultured when available. 7. Measure routine lab tests at local (hospital) laboratory per local custom/SOC collect aliquots f- blood for subsequent biomarker assays (including, but not limited to C-reactive protein [CRP], procalcitonin, interleukin [IL]1β, IL6, IL10, and tumor necrosis factor [TNF]) for analysis at the central laboratory. 8. If eligibility criteria are satisfied, the subject will be randomized 1:1 (rhu-pGSN:placebo) by site to a treatment group and treated within 12 hours of randomization and no later than 48 hours after the diagnosis of moderate-to-severe ARDS. Randomized subjects will receive the assigned dose of rhu-pGSN or an equal volume of visibly indistinguishable sterile saline placebo as soon as possible but beginning no later than 48 hours after the diagnosis of moderate-to-severe ARDS. After reconstitution, rhu-pGSN is not to be kept at room temperature for >2 hours prior to beginning study drug administration. A single loading dose of rhu-pGSN at 24 mg/kg followed by 5 daily doses of rhu-pGSN at 12 mg/kg of measured or estimated actual body weight starting 24 hours after the loading dose or an equal volume of indistinguishable saline placebo will be administered. A window of ±2 hours will be allowed around dosing times. Study drug is administered by an IV push through a 0.2 μm filter. The syringe, filter, and extension tubing for administration of study drug are to be connected as close to the subjects as possible. The primary efficacy endpoint of all-cause mortality will be assessed at Day 28. All-cause mortality will also be assessed on Days 7 and 14. Discharged subjects will undergo follow-up evaluation on Days 14 and 28, preferably but not necessarily in person. Survival at Day 60 will be confirmed by telephonic contact or after 3 failed attempts, review of hospital and public records that document survival or death. Screening laboratory and other tests may be used as baseline values and do not need to be repeated if performed within 24 hours prior to randomization unless otherwise dictated by SOC. However, the blood sample for analysis of pGSN levels is to be repeated if not collected within 15 minutes before initiating the first dose of study drug. Repeat CXRs and/or CT scans and labs/cultures are to be obtained during the hospitalization if/when indicated by SOC. On Days 1 (predose) and 28, blood samples for analysis of antibodies against pGSN are to be collected, if possible. Repeat blood and other cultures should be obtained per SOC. An independent Data and Safety Monitoring Board (DSMB) consisting of at least 2 physicians and 1 statistician with appropriate scientific and medical expertise will be formed, and its roles and responsibilities will be described in the DSMB charter. The DSMB will perform 5 periodic reviews of safety data emphasizing deaths and SAEs and will monitor stopping rules to pause enrollment. There will be no pause on enrollment during the planned unblinded periodic reviews. These reviews will be performed after the first 50, 100, 200, 300, and 400 subjects in the Safety Analysis Set have either completed 28 days of follow-up, have died, or have discontinued from the study prior to completing 28 days of follow-up. DSMB members will be provided with unblinded data. Based on the results of each of the planned periodic reviews, the study will be paused only if there is a relative increase of 25 percentage points in the incidence of death or SAEs in the rhu-pGSN treatment group compared to the placebo group. A futility analysis will be performed at the 300-subject review. The Sponsor will take appropriate action based on the recommendation of the DSMB. The DSMB will also review expedited reports of any SAEs throughout the study and may request additional looks at safety data at their discretion. Enrollment will continue during all safety analyses unless otherwise recommended by the DSMB chair.
Phase
2Span
126 weeksSponsor
BioAegis Therapeutics Inc.Nyiregyhaza
Recruiting
A Study to Customize Ibrutinib Treatment Regimens for Participants With Previously Untreated Chronic Lymphocytic Leukemia
Phase
2Span
251 weeksSponsor
Janssen Research & Development, LLCNyiregyhaza
Recruiting
A Long-term Extension Study of Ustekinumab in Pediatric Participants
Phase
3Span
311 weeksSponsor
Janssen Research & Development, LLCNyiregyhaza
Recruiting
Nyiregyhaza
Recruiting
Nyiregyhaza, Szabolcs-Szatmár-Bereg
Recruiting
A Study of Dostarlimab vs Placebo After Chemoradiation in Adult Participants With Locally Advanced Unresected Head and Neck Squamous Cell Carcinoma
Phase
3Span
278 weeksSponsor
GlaxoSmithKlineNyiregyhaza
Recruiting
Observational Secondary Data Study Describing Treatment With Dapagliflozin Among Adult Chronic Kidney Disease Patients
The OPTIMISE-CKD CEE study design will create a real-world evidence platform that systematically leverages the routine data collection made by Investigators and will help obtain relevant insights from clinical practice. This study is likely to include a more heterogeneous population compared with the constraints required by interventional study protocols. Treatment decisions, clinical outcomes, and common treatment scenarios in the context of routine care of CKD are likely to be more generalizable than those from clinical trials. The results of the study will be used to better inform the medical community, and decision-makers about current and future needs in the CKD management in CEE in real-life setting. The approved label encompasses all CKD patients at risk of disease progression and is thereby broader than the DAPA-CKD trial population. It is important for physicians and patients to better understand dapagliflozin use in CKD in routine clinical practice, particularly among patients who might have been underrepresented in clinical trials. Additionally, payers require additional evidence from the broader CKD population prior to making reimbursement recommendations that will enable access for all patients who have the approved CKD indication. It is important to assess the current CKD treatment with dapagliflozin. Primary objective is to characterize dapagliflozin utilisation in clinical practice, by describing treatment naïve patients who are treated with dapagliflozin for CKD. To describe characteristics among patients newly initiated on dapagliflozin 10 mg for CKD, the following will be used: 1. Baseline demographics and clinical characteristics 2. Baseline laboratory measures 3. Baseline concomitant medications, by drug class and specific drugs of interest. Secondary objectives are to describe selected outcomes of interest and treatment patterns among CKD patients treated with dapagliflozin up to 12 months post-initiation: 1. CKD progression (advancement in CKD stage) 2. Selected clinical outcomes: cardio-renal events (e.g., CKD progression, HF, nonfatal stroke, nonfatal MI) 3. Selected healthcare resource utilization, e.g., all-cause hospitalizations, cardio-renal hospitalizations (CKD, hHF, MACE [nonfatal stroke, nonfatal MI]) 4. Treatment patterns of dapagliflozin, RAASi (ACE inhibitors / ARB), and other selected medications used for CVD and T2D, defined as time to discontinuation (dapagliflozin only), medication additions, discontinuations, and dosage changes. Study design: The OPTMISE-CKD CEE regional study is an observational, longitudinal cohort study with a pre-post design, which will include patients who are treated with dapagliflozin for CKD in real-world clinical practice, utilising secondary data sources in 7 countries (Bulgaria, Croatia, Hungary, Poland, Romania, Serbia and Slovenia) from CEE. The data extraction from medical charts will be made by Investigators, only after eligible patients express their written consent for data collection in the OPTIMISE-CKD study during the enrolment period defined at study level. A period of min. 30 days and max. 90 days after dapagliflozin was initiated is required for enrolment. Given the secondary data collection character of this study, no study-specific diagnostic and monitoring processes are to be applied to the patients. Data Sources: Disease and treatment-related information routinely collected in clinical practice will be extracted by Investigators from paper and/or electronic health records (EHR). Data from all participating centers will be collected into a single anonymized dataset for analysis, by means of electronic case report forms (CRFs). Study Population: Adult patients (aged ≥18 years) with CKD who initiated dapagliflozin 10 mg and meet all inclusion criteria and none of the exclusion criteria. Enrolment is to be performed minimum 30 days and maximum 90 days since initiation of dapagliflozin for CKD. Previous treatment with dapagliflozin or SGLT-2i deems patient ineligibility. Exposure(s): The study will describe CKD treatments and drug utilisation patterns (Section 4.2), specifically for dapagliflozin 10 mg, RAASi and other treatments routinely used in the management of CKD patients (see Section 4.4) up to 12 months post-dapagliflozin initiation. Data on exposure to dapagliflozin, RAASi, and other CKD/CVD/T2D-related treatments prescribed as part of routine care will be collected. In all cases, the decision to treat a patient with dapagliflozin will be made prior to the decision to enroll a patient into the study. All treatment decisions are at the discretion of the current patient's physician, based on clinical judgment and recommendations included in the approved label and national treatment protocols, and are not mandated by this protocol. Study measures: - Baseline demographic, clinical characteristics, comorbidities and medications - Post-index medications (changes, including addition, and discontinuation, and time to discontinuation for dapagliflozin) - Post-index cardio-renal events - Post-index healthcare resource use Sample Size Estimations: This study does not involve hypothesis testing. No formal sample size and power calculations have been performed. Across participating CEE countries (Bulgaria, Croatia, Hungary, Poland, Romania, Serbia and Slovenia), an estimated number of 1090 patients is planned for inclusion, with country target numbers varying between 70 and 300 patients, depending on preliminary feasibility with sites, the size of the country and reimbursement status at study start and during the study. The target number of patients is planned to be enrolled in 6-8 months across the region. If this target sample is not reached, this does not imply study failure, but the precision on estimates will change. Statistical Analysis: The statistical analyses will be fully described in the Statistical Analysis Plan (SAP) as appropriate. Descriptive analyses will be performed to describe the characteristics of the cohort studied. Continuous variables will be summarized using means with standard deviations (SDs), medians with interquartile ranges (IQR), and minimum and maximum values. The number and percentages of patients will be used to summarize categorical variables, including a separate category for patients with missing data at baseline. Missing data will be quantified for all study variables, but there will be no attempts to impute them. For the secondary objective, the time to discontinuation will be estimated using the Kaplan-Meier method. Summary statistics will be used to describe proportions of patients with the event changes within the set time windows. Baseline demographic and clinical characteristics will be summarized on the index date. For laboratory data, the value closest to index (in the last year before or on the index date) will be used. Comorbidities and medical history will be summarized in the last year before index date. Stratified analyses based on baseline demographic and clinical characteristics may be performed. Summary statistics will be used to describe treatment patterns and drug utilisation. Further specification on planned analyses will be provided in the SAP
Phase
N/ASpan
93 weeksSponsor
AstraZenecaNyiregyhaza
Recruiting
ELEMENT-MDS: A Study to Compare the Efficacy and Safety of Luspatercept in Participants With Myelodysplastic Syndrome (MDS) and Anemia Not Receiving Blood Transfusions
Phase
3Span
333 weeksSponsor
Bristol-Myers SquibbNyiregyhaza, Szabolcs-Szatmár-Bereg
Recruiting
Nyiregyhaza
Recruiting
Nyiregyhaza, Szabolcs-Szatmár-Bereg
Recruiting