Lincoln Park, New Jersey

A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

JNJ-90301900 (NBTXR3) Activated by Radiotherapy With or Without Cetuximab in LA-HNSCC

Participants will undergo a screening assessment over a period of less than or equal to (<=) 28 days to determine eligibility. Eligible participants will be treated by the Investigator's choice of RT alone or RT in combination with cetuximab. Following the Investigator's choice, participants will be randomized in a 1:1 ratio: - Arm A: JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab - Arm B: Investigator's choice of RT alone or RT in combination with cetuximab All participants (Arm A and Arm B) will receive 70 Gy in 35 fractions over a 7 week period. An EOT visit will be performed 4 weeks after the completion of RT. Follow-up visits will start at 12 weeks post-RT completion, and will continue every 12 weeks for 2 years, and then every 24 weeks thereafter until death; the participant is determined to be lost to follow up; withdrawal of consent; or the end of the study, whichever occurs first. Participants who have received further anti-cancer therapy for the study disease and/or have had disease progression/recurrence will be followed only for survival information

A Cardiac Registry to Evaluate and Manage the hsTnI Categorical CVD Risk in Subjects Undergoing Preventive Health Checks (PHC).

Development of high-sensitivity assays for cardiac troponin I (hs-TnI) has enhanced the ability to detect low circulating levels of cardiac troponins, which are often present in individuals with common cardiac conditions and risk factors who have not manifested clinical cardiovascular disease (CVD). Lowering the detection threshold of troponin assays has expanded the potential use of cardiac troponins from a diagnostic tool in the setting of acute coronary syndrome to a biomarker for risk stratification in individuals without known CVD. Detectable levels of cardiac troponins have been associated with increased incidence of coronary heart disease (CHD), heart failure (HF), and cardiovascular mortality in community-based studies. Traditional cardiovascular risk prediction does not identify everyone who will develop cardiovascular disease with up to 50% of individuals having none or only one risk factor at the time of diagnosis. Although traditional risk estimations perform moderately well, there remain significant limitations in their use in the prevention of cardiovascular disease especially at an individual level. At an individual level, the clinician not only needs to correctly identify those at increased risk, but also weigh up the importance of each risk factor and determine who needs medical therapy in addition to lifestyle advice Many risk estimation systems in existence are based on a core set of cardiovascular risk factors and based on participants either selected randomly from the general population or those attending their general practitioner. All these risk scoring systems show a good level of discrimination, for cardiovascular events, with the area under the receiving operator curve ranging from 0.73 to 0.82. However, adopting these risk scoring systems to guide current clinical practice has limitations. First, most of these scoring systems, except QRISK1 and QRISK2 have been developed from old prospective cohorts with participants recruited in the 1980's and 1990's Second, applying risk estimation scores to regions with different rates of baseline rates of cardiovascular disease will lead to either under- or over-estimation of risk: a result of mis-calibration. Third, the value of incorporating new risk factors including biomarkers such as high-sensitivity C reactive protein has been disappointing in improving discrimination, with age and sex alone contributing to 0.70 of the area under the receiver operating curve statistic. None of these risk estimation scores, to date, incorporate a direct measure of cardiac injury such as cardiac troponin and its potential role in guiding primary prevention in a contemporaneous population remains uncertain.

Liver Transplantation in Patients With CirrHosis and Severe Acute-on-Chronic Liver Failure: iNdications and outComEs

The aim of this study is to compare 1-year graft and patient survival rates after liver transplantation (LT) in patients with ACLF-2 or 3 at the time of LT, with patients with decompensated cirrhosis without ACLF-2 or 3 at the time of LT and also with transplant-free survival of patients with ACLF-2 or 3 not listed for LT. Secondary objectives are as follows: - To assess the proportion of patients with ACLF-2 or 3 referred to transplant team who are listed or not and reasons of this decision. - To evaluate the outcomes of patients listed with ACLF-2 or 3 on the waiting list compared with those of patients listed with decompensated cirrhosis without ACLF-2 or 3. - To define independent predictive factors of death/delisting on the waiting list for patients listed with ACLF-2 or 3 and develop a new prognostic model based on ACLF criteria to predict mortality on the waiting list and to improve the allocation of organs. - To compare the characteristics of accepted grafts for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3 and their impact on post-LT outcomes. - To explore independent predictive factors of death after LT for patients transplanted with ACLF-2 or 3 to design futility criteria for LT. - To compare post-LT survival rates of patients with ACLF-2 or 3 at listing and patients without ACLF at listing who develop ACLF-2 or 3 on the waiting list. - To compare post-LT quality of life (QoL) for patients listed with ACLF-2 or 3 with those of patients listed with decompensated cirrhosis without ACLF-2 or 3.

To Evaluate the Efficacy and Safety of MaxioCel Versus Aquacel Extra for the Management of Chronic Wounds

The current study intends to compare the efficacy of the chitosan wound dressing (MaxioCel) with another marketed dressing (Aquacel Extra). MaxioCel is made up of chitosan and Aquacel Extra with carboxymethyl cellulose. Both are polymeric dressings.

Erythropoietin for Neonatal Encephalopathy in LMIC (EMBRACE Trial)

The burden of neonatal encephalopathy is far higher in low and middle-income countries. Recently, the Hypothermia for Encephalopathy in Low and Middle-Income Countries Trial (HELIX) study concluded cooling therapy did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries. In fact, the results found that cooling therapy significantly increased death alone. This warrants exploration of the efficacy of other treatment adjuncts for these settings. One medication with potential for monotherapy is Erythropoietin. Erythropoietin is an erythropoiesis stimulating cytokine used for the treatment of anaemia. It is a Food and Drug Administration (FDA) approved drug that is widely used for treatment of anaemia including premature babies and has extensive safety profile in newborn babies. Erythropoietin is also produced by neurons and glia in the hippocampus, internal capsule, cortex, and midbrain in response to hypoxia. More recently, erythropoietin has been reported as having anti-apoptotic, anti-inflammatory and anti-oxidative effects, making it a prime neuroprotective candidate. It also reduces free iron accumulation which occurs due to hypoxic ischemia by inducing erythropoiesis, which promotes neurogenesis. Extensive preclinical small and large animal models have demonstrated neuroprotective and neuro reparative effects of Erythropoietin when used as monotherapy. A number of small randomised controlled trials have been reported from low and middle-income countries. A systematic review and meta-analysis of Erythropoietin monotherapy in babies with neonatal encephalopathy in LMIC showed pooled data including a total of 348 babies from 5 clinical trials in LMIC suggest 40% relative risk reduction (Risk Ratio 0.62 (95% Confidence Intervals (CI) 0.40 to 0.98) in death or disability at 18 months with Erythropoietin, compared with placebo. None of these clinical trials have reported any serious adverse events of Erythropoietin monotherapy. Erythropoietin dose used in these trials varied from 300U/kg to 2500U/kg, single dose to a maximum of two weeks of duration starting within 24 hours after birth. The largest of these trials, reported from China have used a low dose (500U/kg) on alternate days for two weeks. This trial recruited 153 babies with moderate or severe encephalopathy and reported that Erythropoietin significantly reduced death or disability at 18 months. More recently, another randomised controlled trial of Erythropoietin involving 62 normothermic babies with moderate or severe neonatal encephalopathy has been reported from Government Medical College, Aurangabad in India. The investigators used an Erythropoietin dose of 500 U/kg alternate days for 10 days starting within 24 hours. Neonatal mortality was significantly lower (39%; 12/31) in the Erythropoietin group compared with the placebo group (71%; 22/31) (p=0.01). No adverse events were reported in the Erythropoietin group. The EMBRACE trial is a phase III, multi-country, double-blinded, placebo-controlled randomised controlled trial of Erythropoietin versus sham injection (placebo) in babies with neonatal encephalopathy in low and middle-income countries. All clinical and study team except for the nurse administering the trial drug will be masked to the intervention. The investigators plan to randomise 504 babies in this trial. The dosing regimen will be IV/Sub cutaneous Erythropoietin 500unit/kg within 6 hours of birth and then daily until 8 days. In total, there will be 9 doses. Body temperature of all babies will be monitored 4 hourly for the first three days after birth and normothermia (36.0-37.5°C) will be maintained as a part of the usual care at these hospitals with an algorithm to prevent/treat hyperthermia. Magnetic resonance biomarkers including spectroscopy and diffusion tensor imaging will be acquired between 1 to 2 weeks of age in all recruited babies. The MR scanners and sequences at each site will be harmonised prior to recruitment. The trial will have an 18 month recruitment period, a 18 month follow-up period, and 5 months for data analysis and write up. A pilot study (external pilot) of 50 babies will be done prior to the start of the EMBRACE trial (Jan 2023 to April 2023) but these patients will not be included in the main trial. Minor updates to the trial protocol may be made after the completion of the pilot trial.

Phase IV Panitumumab Study in Indian Subjects With Metastatic Colorectal Cancer

This is an open label, multicenter, non-comparative, phase IV study of panitumumab monotherapy in Indian subjects with previously treated, wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) and wild-type Neuroblastoma rat sarcoma viral (v-ras) oncogene homolog (NRAS), metastatic colorectal cancer. This study is designed to fulfil the requirement of the Indian regulatory authority to characterize the safety and tolerability of panitumumab when administered to Indian subjects with wild-type KRAS and wild-type NRAS metastatic colorectal cancer. Approximately 58 Indian subjects with previously treated wild-type KRAS and wild-type NRAS, metastatic colorectal cancer will be enrolled in order to achieve the target enrollment of 50 evaluable subjects who have received at least one dose of panitumumab. Subjects will receive panitumumab 6 milligram/kilogram (mg/kg) intravenously every 14 days until disease progression, intolerability, withdrawal of consent, or death. All subjects will be followed at 4 weeks and 8 weeks after the last administration of panitumumab, unless the treatment was discontinued due to withdrawal of consent or death of the subject. All adverse events occurring from signing of informed consent form until 8 weeks after last dose of panitumumab will be recorded. All Serious Adverse Events (SAE) considered related to panitumumab by the investigator or the sponsor will be followed until the event resolves, or is considered stable or until the subject is lost to follow-up or withdraws consent.

Product Surveillance Registry

Bacteriophage Therapy TP-102 in Patients With Diabetic Foot Infection

This is a Phase 2b, double-blinded, randomised, placebo-controlled multicenter study to determine the safety and efficacy of TP-102, in patients with diabetic foot infection. Eighty (80) patients with an infected diabetic foot ulcer and with at least one target bacterial strain (Pseudomonas aeruginosa, Staphylococcus aureus or Acinetobacter baumannii) susceptible to TP-102. Patients will be randomised to receive TP-102 or placebo, in a 1:1 ratio. Patients will be treated with 1 (one) mL of IP/ Placebo solution applied topically per cm3 of target ulcer. Patients will be treated with a total of 12 treatments in 28 days (+3 days) with at least one day of interval in between the days of treatment (no consecutive days of treatment are allowed) and a maximum of 3 (three) days without treatment. The titre of each bacteriophage in TP-102 is 1x109 (>1x108 and < 1x1010) plaque forming units per milliliter (PFU/mL). Assessments for efficacy and safety will include concomitant medications and AEs, local tolerability, clinical laboratory tests, vital signs, physical examination, wound biopsy/swab to determine the presence, speciation and TP-102 sensitivity of bacteria and target ulcer assessment.

Feasibility Clinical Evaluation of the Calibreye System

This is a prospective, nonrandomized, open-label feasibility clinical trial, to evaluate the surgical procedure, safety and effectiveness of the Calibreye System in reducing intraocular pressure in subjects with open angle glaucoma.