Kazan N/a, Russian Federation

Screening for Islet Autoantibodies in the Israeli Paediatric General Population for Detection of Pre-symptomatic Type-1 Diabetes Mellitus

A Global Phase III Study of Rilvegostomig or Pembrolizumab Monotherapy for First-Line Treatment of PD-L1-high Metastatic Non-small Cell Lung Cancer

This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab as a 1L treatment for patients with mNSCLC whose tumors express PD-L1.

A Study of JNJ-79635322 in Combination With Daratumumab or Pomalidomide for Multiple Myeloma

Paromomycin or Metronidazole for Symptomatic Dientamoeba Fragilis in Adults

Introduction Dientameba Fragilis (D.fragilis) is a protozoan found in the digestive tract - in the human colon. The route of transmission is fecal-oral, and infection can lead to chronic gastrointestinal symptoms manifested by abdominal pain, diarrhea, abdominal bloating, anal pruritus, and in addition pronounced fatigue [1]. Since the introduction of a molecular diagnosis [PCR] for a stool test, it has become clear that these protozoa are a main protozoa inhabiting the digestive system, with stool positivity rates ranging from 12 to 68%, depending on country and age [2]. This parasite was first identified about 100 years ago and since then debates have continued in the medical literature as to whether it is indeed a pathogen or a commensal [3]. In addition, there are disagreements regarding the preferred treatment for these cases, with several regimens tested in mostly small observational studies. Several drugs are currently recommended for D.fragilis, with metronidazole most commonly used [4]. However, metronidazole therapy for treating dientamoebiasis in children was not associated with better clinical outcomes in a randomized, double-blinded and placebo-controlled clinical trial. Furthermore despite observing higher eradication rates two weeks after end of therapy with metronidazole in this trial, positivity rebounded quickly appeared after therapy. [5]. In contrast, several observational studies have reported high clinical and microbiological success rates with paromomycin, with over 80% eradication in adults [6,7]. We could not identify any prospective study comparing head to head these two drugs; metronidazole and paromomycin. In light of the above, we plan to perform a double blind, randomized controlled trial, evaluating the clinical and microbiological efficacy of paromomycin versus metronidazole for the treatment of symptomatic adults with PCR positive dientamoeba fragilis. The primary outcomes is clinical improvement or resolution (yes/no. Secondary outcomes include clinical improvement evaluated by a visual analogue scale; microbiological eradication, quality of life, and adverse events related to therapy. Aim - To evaluate clinical response to paromomycin versus metronidazole treatment. - To evaluate whether paromomycin is superior to metronidazole in eradicating D. fragilis in molecular stool testing (PCR) 3-4 weeks after end of therapy. - Additional aim is to evaluate the relationship between clinical cure and eradication of the parasite. Design: Double-blind Randomized Controlled study comparing metronidazole vs. paromomycin treatment in patients with prolonged gastrointestinal symptoms and positive D. fragilis in molecular (PCR) stool test. Patients will be approached through social networks advertisements, infectious diseases and gastrointestinal clinics, inviting individuals suffering from gastrointestinal symptoms over one month who had a positive PCR test for D. fragilis in the previous 6 months. These patients will be invited for a clinic visit. Population: Inclusion criteria: Patients over the age of 18, not including pregnant women - With persistent gastrointestinal symptoms (over one month). - Without any other clear diagnosis to explain these symptoms according to medical records. - With a positive PCR stool test for D. fragilis without any additional pathogen (patients with Blastocystis hominis in feces will not be excluded). Exclusion criteria: - Pregnancy - Hypersensitivity to any of the study drugs or to aminoglycosides - Patients age below 18 years - Metronidazole or paromomycin treatment in the last 3 months Intervention: After signing informed consent, study participants will fill out symptoms questionnaire, built in 4-point Likert scale (See Appendix). We will randomize them into two treatment arms: paromomycin and metronidazole. Randomization will be generated by computer and will be central. Study allocation will be blinded from patients, principal investigators and outcome assessors. Medical treatment planned for 7 days as follows: 1. Metronidazole 500mg X3 / day 2. Paromomycin 500mg X3 / day In both preparations the pill is 250 mg, so both treatment arms will have the same number of tabs and same length of treatment. Patients will be provided with the drugs for 7 days (we will examine the possibility of making it identical in appearance). Follow-up 1. Monitoring side effects for each drug - using a questionnaire. This will be conducted by telephone at the end of the treatment (one week) by a research assistant (without passing the information to the doctor - to prevent revealing of blinding). 2. In person meeting with a study physician 3-4 weeks after completion of treatment, at which time the patient will fill out a structured questionnaire for symptom evaluation (See Appendix). The physician will be blinded to the patient's treatment. Clinical improvement will be defined as improvement in the Likert scale in at least one symptom, with no exacerbation in any other symptom. 3. Repeated PCR stool test 3-4 weeks after the end of treatment. 4. An additional similar visit will be held at 8 and 12 weeks after end to treatment. Sample size calculation for superiority: In order to show superiority of paromomycin with 90% power and an Alpha of 5%, assuming 80% clinical improvement with paromomycin versus 40% with metronidazole, a sample size of 27 patients per arm will be required. Considering a dropout rate of up to 10%, we estimate a sample size of 60 patients.

Intra-articular Allocetra in Osteoarthritis of the of the Temporomandibular Joint (TMJ)

The temporomandibular joint (TMJ) is a critical synovial joint enabling jaw movement. TMJ osteoarthritis results from factors such as disc dislocation, trauma, overuse, or developmental anomalies, affecting all joint structures, including cartilage, synovium, bone, and ligaments. Key pathological features include chondrocyte loss, extracellular matrix degradation, and subchondral bone remodeling. TMJ-OA progresses gradually through phases of activity and remission, ultimately leading to a burnout phase. Allocetra is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state. This study is a single center, open lable safety and initial efficacy trial to assess intra-articular administration of Allocetra in patients with TMJ-OA who have not responded sufficiently to conventional therapies. The study is comprised of two stages, during which a single treatment of Allocetra, will be administered via intra-articular injection into the target temporomandibular joint. Patients will be followed for up to a year following treatment.

A Study of Nipocalimab in Reducing the Risk of Fetal and Neonatal Alloimmune Thrombocytopenia (FNAIT)

Tuvusertib Combined With Niraparib or Lartesertib in Participants With Epithelial Ovarian Cancer (DDRiver EOC 302)

A Study of TAK-279 in Participants With Moderate-to-Severe Plaque Psoriasis

This study consists of 2 parts: Part A and Part B. Part A: Participants who did not participate in either parent study (TAK-279-3001 [NCT06088043] or TAK-279-3002 [NCT06108544]) may be enrolled and will be treated for up to 52 weeks. Participants who successfully complete Part A of the study are eligible to continue in Part B, but investigators must confirm their eligibility to continue in Part B. Part B: Participants who complete the treatment period of TAK-279-3001 (NCT06088043) or TAK-279-3002 (NCT06108544) parent studies or who complete Part A are eligible to enroll directly into open label extension treatment in Part B and will be treated for up to 156 weeks.

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

A Platform Trial for Gram Negative Bloodstream Infections

BALANCE+ is an adaptive platform trial evaluating multiple treatment options in patients admitted to the hospital due to Gram negative bloodstream infections (BSIs). It focuses on both cross-cutting and subgroup-specific questions, using an open-label, pragmatic design embedded in routine care. BALANCE+ addresses the significant health concern of BSIs, which have high morbidity and mortality rates, exacerbated by the global public health threat of antimicrobial resistance (AMR). With rising resistance rates and limited new drug development, effective treatment strategies for BSIs remain under-researched. BALANCE+ follows the BALANCE trial, which evaluated duration of antibiotic treatment, and aims to further investigate critical questions in managing Gram-negative BSIs. This platform trial will explore various aspects of BSI treatment, including antibiotic de-escalation, oral antibiotic choices, central line management, treatment of specific pathogens, and the necessity of follow-up blood cultures. BALANCE+ is using Bayesian methods without a fixed sample size. Interim analyses will occur after every 1000th patient in each domain, and then for every 200th patient thereafter. The trial will stop if futility or superiority thresholds are met, or if a domain reaches its ceiling sample size (2500 patients for most domains and 4000 for the beta-lactam versus non-beta-lactam domain) without meeting a stopping threshold. A vanguard pilot trial involving over 150 patients at 9 hospitals across Canada confirmed the feasibility of the BALANCE+ trial. The main trial will include patients from the vanguard pilot phase since there has been no major change in the overall study design and domains. The adaptive design allows for interim analyses and adjustments by adding or removing domains as per the statistical analysis plan, enhancing the trial's efficiency and relevance.