Niederstetten, Germany
A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)
Phase
1/2Span
211 weeksSponsor
Merck Sharp & Dohme LLCRamat Gan
Recruiting
Novel Epigenetic Mapping in Cell-Free DNA for the Detection of Lung Cancer
During cell death, which occurs frequently in cancerous tissue, DNA from the dead cells is released into the blood. This DNA has a unique epigenetic pattern that can indicate the tissue of origin from which it was released. Therefore, cell-free DNA may serve as a biomarker for monitoring tissues in which there is increased cell death and allow for early detection of disease before it is even visible by other existing methods. In addition, because the epigenetic pattern is dynamic and changes depending on the existing condition, epigenetic changes may allow the identification of the type of disease or serve as a marker for responsiveness to treatment. The aim of the proposed study is to perform epigenetic mapping in cell-free DNA to identify genomic regions that differ in their epigenetic pattern between lung cancer patients of all histological types, patients with chronic lung diseases, patients with acute pneumonia, and healthy individuals. In particular, the ability to assist existing methods in cancer diagnostics, predict response to treatment, and assess the success of treatment during and after treatment will be examined. In addition, the ability to assess minimal residual disease (MRD) will be examined by taking blood after surgery to remove a tumor or after treatment and testing whether there is any residual DNA from the tumor using the markers that are found. This method may allow early identification of MRD in lung cancer by cell-free DNA in the blood, thus influencing the method of treatment and significantly increasing the chances of survival for patients. Subjects will be screened for eligibility and then, after signing an Informed Consent Form, the first peripheral blood sample will be obtained. Lung cancer patients undergoing treatment will donate blood at the following time points: before starting their first systemic treatment (immunotherapy/chemo-immunotherapy) treatment, 4-12 weeks after treatment initiation, and 6-12 months post-treatment. Lung cancer patients undergoing surgery to remove lung cancer will donate blood at the following time points: before the surgery, 4-6 weeks after surgery, and 6-12 months post-surgery. Patients with positive or inconclusive low-dose CT findings and negative biopsy results for lung cancer will be recruited to evaluate the ability of the test to assist in a more accurate diagnosis. Patients with chronic lung disease or acute pneumonia, with no lung cancer diagnosis and 50 healthy volunteers will be recruited as control groups. These participate will donate blood once during the study.
Phase
N/ASpan
83 weeksSponsor
JaxBio LtdRamat Gan
Recruiting
Healthy Volunteers
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.
Phase
3Span
295 weeksSponsor
AstraZenecaRamat Gan
Recruiting
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.
Phase
N/ASpan
210 weeksSponsor
Sunnybrook Health Sciences CentreRamat Gan, Tel Aviv
Recruiting
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.
Phase
3Span
88 weeksSponsor
TakedaRamat Gan
Recruiting
Ramat Gan
Recruiting
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.
Phase
N/ASpan
154 weeksSponsor
Sheba Medical CenterRamat Gan
Recruiting
A Study of JNJ-79635322 in Combination With Daratumumab or Pomalidomide for Multiple Myeloma
Phase
1Span
174 weeksSponsor
Janssen Research & Development, LLCRamat Gan
Recruiting
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.
Phase
1Span
69 weeksSponsor
Dr. Amit DruyanRamat Gan
Recruiting
A Study of Zasocitinib in Adults With Psoriatic Arthritis Who Have Not Taken Biologic Medicines
Phase
3Span
152 weeksSponsor
TakedaRamat Gan
Recruiting