Rabka-zdrój, Poland
Relationship Between Immunosuppressive Treatment Status and Clinical Course of Parkinson's Disease
Phase
N/ASpan
187 weeksSponsor
Medical University of WarsawWarsaw
Recruiting
Efficacy and Safety of KBP-336 in Obese Individuals with Osteoarthritis
Phase
2Span
101 weeksSponsor
KeyBioscience AGWarsaw
Recruiting
Cord Blood S100B Protein Concentration in Neonates With Fetal Growth Restriction
Phase
N/ASpan
93 weeksSponsor
Institute of Mother and Child, Warsaw, PolandWarsaw
Recruiting
Impact of Knee Extension Brace on Quadriceps EMG During ASLR
The study will be conducted on a group of healthy individuals aged 18 - 35 years. After an interview confirming that the subject does not have exclusion criteria and written consent to participate in the study, anthropometric measurements will be taken of height and weight using a scale and tape measure. The subjects will be informed in detail about the procedure and the form of the measurements, the way in which they are to be taken, and will be familiarised with the the measuring instruments and their principles of operation. Then, in accordance with the study protocol, specific measurements will be taken of the rectus femoris, medial vastus and lateral vastus muscles using surface EMG of a non-invasive nature. Study participants will undergo the following measurements: 1. Measurement of the MVC (maximum voluntary contraction) of the quadriceps of the thigh, in a sitting position with the lower leg flexed to 90 degrees. 2. Measurement of muscle activity during elevation of the straightened lower limb in a supine position without an orthosis. 3. Measurement of muscle activity during straight leg raise in supine position with knee brace. Ad.a. Measurement of quadriceps excitability of the dominant lower limb using surface EMG in a seated position with the trunk stabilised and the lower leg flexed to 90 degrees, stabilised in the distal part (without taking the foot) against a stationary object so as to execute maximal volitional isometric quadriceps muscle tension. Upper limbs crossed over the chest. Ad.b. Measurement of right quadriceps excitability using surface EMG in supine position without orthosis. The subject raises the test limb by touching the anterior surface of the tibia to a pole set at 20 cm at the command 'raise leg', then lowers the limb at the command 'lower leg'. During the task there is a 1 second moment of holding the leg straight as the tibia touches the pole. This action is repeated three times. Ad.c. Measurement of quadriceps excitability of the dominant lower limb using surface EMG in supine position with knee extension brace on. Measurement performed in three variants: 1. The test subject raises the test limb by touching the front surface of the tibia to a pole set at a height of 20 cm on the command 'raise leg', then lowers the limb on the command 'lower leg'. During the task there is a 1 second moment of holding the leg straight as the tibia touches the pole. This action is repeated three times. 2. The test subject is asked to apply maximum tension to the quadriceps (thigh muscle) (command 'press the knee against the ground, bring the toes together, straighten the foot and flex the quadriceps maximally"), then maintaining the tension he/she raises the limb touching the front surface of the tibia to the pole placed at the height of 20 cm on the command "raise the leg", then lowers the limb on the command "lower the leg". During the task there is a 1 second moment of holding the leg straight as the tibia touches the pole. This action is repeated three times. 3. Before the test, the test subject is verbally instructed to 'Try, despite the orthosis holding you upright, to bend the knee and raise the leg so that the quadriceps do not tense'. Then, on the command 'raise leg', the test subject raises the limb by touching the front surface of the tibia to a pole set at 20 cm, on the command 'lower leg' he lowers the limb. During the task there is a 1 second moment of keeping the leg straight as the tibia touches the pole. This activity is repeated three times. The time for the full test is approximately 15-20 minutes per participant. Statistical analysis will be performed using Statistica and/or JASP software. The study will be carried out with a minimum of 20 adults aged 18 - 35 years. The exact number of participants in the study, will be determined after performing an a-priori sample size estimation after collecting data from the first 10 people examined. Eligibility of subjects will include a subject and physical examination by a physiotherapist. Inclusion criteria: age between 18-35 years, no contraindications to physical exercise, ability to perform the required commands without pain or discomfort, full range of motion of the knee joint. Exclusion criteria: those with a history of knee and/or hip surgery, damage to ligamentous structures of the knee joint in the past treated conservatively or meniscus treated conservatively, muscle and tendon injury of the knee joint area in the past 3 months.
Phase
N/ASpan
48 weeksSponsor
Józef Piłsudski University of Physical EducationWarsaw
Recruiting
Healthy Volunteers
Local, Targeted Therapy With Alpha Emitter [225Ac]Ac-DOTA-SP (TAT) in Glioma (WHO G3-G4) Progression
1. Background: Brain tumors account for 1.35% of all cancer conditions and cause deaths in 2.2% of cancer patients (Cancer Facts and Figures 2005). The most common type of brain tumors are gliomas. Depending on the age group, they account for 40%-90% of central nervous system tumors. The incidence of malignant gliomas is 0.5-2 per 100,000 people per year. Men are more frequently affected, usually in their 50s and 60s. In the Polish population, approximately 1300 people are diagnosed with gliomas annually, including about 600 cases of malignant gliomas. The standard treatment approach includes surgical treatment, radiotherapy, and chemotherapy. Despite the currently accepted treatment regimen, survival times-depending on the tumor type-range from 1 to 3 years. In a typical course, regardless of the therapy used, the extent of surgery, and other prognostic factors, the progression of the growth process occurs after some time. The use of chemotherapy extends survival time-depending on the tumor type-by several to several dozen weeks. This data indicates the need to seek other forms of treatment. Since brain gliomas are infiltrative in nature, it seems that an effective drug should exhibit the ability to diffuse freely within the tumor and specifically bind to cancer cells. Selected peptides exhibit such properties. One of the mechanisms regulating cell (including cancer cell) function involves receptor systems located in the cell membrane. These show high specificity of reaction with specific peptides. The expression of some receptor systems significantly increases in cells of specific tumor types. This property underlies the use of radioisotope-labeled peptides in diagnosis and treatment in oncology. Peptides bind to cancer cells, and ionizing radiation emitted by the attached radioisotope leads to regression of pathological changes. This method is developed only in a few centers worldwide and is currently used, among others, in treating certain types of lymphomas (anti-CD-20 antibody labeled with 90Y or 131I) and neuroendocrine tumors (somatostatin analogs labeled with 90Y, 177Lu). The benefit of this method is the ability to treat tumors that exhibit resistance to conventional chemotherapy and radiotherapy. Based on own experiences and literature data, it is known that gliomas show increased expression of selected receptor systems. In grade II-IV gliomas, a significant increase in expression for neurokinin-1 (NK-1) receptors, for which substance P is the ligand, has been noted. When administered directly to the tumor, substance P undergoes rapid diffusion and binding to glioma cells. At the center in Basel (Institute of Nuclear Medicine, University Hospital Basel), a derivative of substance P (1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid) was developed. It was shown that over 95% of gliomas exhibit significantly increased expression of the NK-1 receptor system, and that the proposed peptide has a capacity for specific binding to this type of receptor (out of 34 glioma tissue samples, 32 samples showed significantly increased NK-1 receptor system expression). Substance P can be labeled with various radioisotopes with differing physical properties, including 90Y and 177Lu-beta radiation emitters. The beta radiation emitted by 90Y has an energy of 2.1 MeV, with a tissue range of about 12 mm. Lutetium emits radiation with an energy of 497 keV, with a range of 1 mm. Limiting factors for the use of beta radiation include its range of action. There is a potential risk of damage to functionally critical brain centers if the tumor is located nearby. This was a premise for the use of alpha radiation emitters. One of the studied radioisotopes is 213Bismuth, which has an energy of 5.8 MeV but a range limited to only 81 μm. To date, within the framework of the project "Use of Radioisotope-Labeled Substance P in Treating Patients with Brain Tumors" (KB/204/A/201), local glioma treatment has been provided using substance P labeled with alpha emitters 213Bi and 225Ac in the case of confirmed disease recurrence. Initially, local treatment was performed using [213Bi]Bi-DOTA-SP at an activity of up to 11.2 GBq, achieving good treatment tolerance without clinically significant side effects. The progression-free survival (PFS) was 2.7 months, and the median overall survival (OS) after disease recurrence was nearly twice as long as expected in this patient group, amounting to 10.9 months. The median overall survival from diagnosis was 23.6 months. However, after the start of treatment with [213Bi]Bi-DOTA-SP, the median survival was 7.5 months. Considering the difficulties in labeling and quality control with a short half-life for 213Bi (46 min), the next step involved treatment with the alpha-emitter 225Ac. A study was conducted evaluating the determination of the maximum tolerated dose of [225Ac]Ac-DOTA-SP, administering activities of 10 MBq, 20 MBq, and 30 MBq. The treatment was well tolerated by patients, with predominantly mild and transient adverse effects such as seizures, aphasia, and hemiparesis. Most adverse effects occurred in patients treated with the 30 MBq dose of [225Ac]Ac-DOTA-SP; hence, the maximum tolerated dose was determined to be 20 MBq. Thrombocytopenia of grade 3 was observed in one study participant, and no grade 3 or 4 toxicity related to the treatment with [225Ac]Ac-DOTA-SP was reported in the other participants. The median OS from diagnosis was 35 months, and from recurrence, it was 13.2 months. The PFS from the start of treatment with [225Ac]Ac-DOTA-SP was 2.4 months. Studies showed that despite different physical properties (213Bi T1/2 = 46 minutes, 225Ac T1/ 2 = 9.9 days, with 225Ac decaying through alpha particles and 213Bi decaying only once), the survival data for patients treated with [225Ac]Ac-DOTA-SP and [213Bi]Bi-DOTA-SP are similar. Theoretically, the significantly longer half-life of 225Ac should allow for better distribution of [225Ac]Ac-DOTA-SP. The diffusion of the administered radiopharmaceutical is a critical factor for effective local therapy and depends on several factors, such as molecular weight, physicochemical properties, varying extracellular space density, and the post-resection cavity. Small vectors, such as modified SP (1800 Da), lead to rapid diffusion within tissues. However, subsequent administrations may increase the density of the extracellular space due to glioma scarring, leading to heterogeneous diffusion in subsequent injections of the radiopharmaceutical. A limiting factor for local treatment is the very slow rate of diffusion into brain tissue. The diffusion rate in the brain for most substances ranges from 0.15 to 0.6 mm/h. One possible cause could be increased tissue pressure within the tumor and surrounding tissues, which reduces the pressure gradient responsible for the diffusion process. It seems that enhanced diffusion could be achieved by employing forced diffusion via a slow infusion of 0.5 ml/hour of saline into the cavity immediately after administering the radiopharmaceutical. Overall results from both treatment arms exhibit a clear trend for prolonged survival compared to standard therapy. . 2. Main Objective: To evaluate the efficacy of local targeted therapy with the alpha-emitter labeled neuropeptide [225Ac]Ac-DOTA-SP (TAT) using a forced diffusion method in cases of recurrence of glioma WHO G3-G4 after first-line treatment. Secondary Objective: To assess the safety of local targeted therapy with the alpha-emitter labeled neuropeptide [225Ac]Ac-DOTA-SP (TAT). . 3. Study Design: Interventional study without a control group. The study is initiated by the investigator, and 225Ac is supplied based on a cooperation agreement between WUM and the Institute for Transuranium Elements (Karlsruhe). Sponsoring institution: Medical University of Warsaw (WUM). . 4. Conducting the Study: 1. Qualification visit - gathering a medical history, summarizing previous diagnostics and treatments - necessary documentation from the treatment course and imaging studies (CT scans and/or MRIs) must be provided. During the discussion, the doctor will provide all necessary information regarding the study and answer any questions. 2. Reoperation with Catheter Placement: PET/CT scan using [68Ga]Ga-PSMA to indicate the site for biopsy and catheter placement. Resection with biopsy or just the biopsy of the tumor. Cathether placement (for lesions with a diameter >2 cm, up to 3 catheters may be placed). Catheter placement will take place at the Departments of Neurosurgery of either University Clinical Centre (UCK) or National Oncology Institute (NIO). This requires several days of hospitalization. 3. Local Treatment with [225Ac]Ac-DOTA-SP: Treatment with [225Ac]Ac-DOTA-SP cannot begin earlier than 2 months after the conclusion of radiotherapy. Chemotherapy may be continued according to the oncologist's recommendations. Catheter patency controle about one week before planned treatment. Local administration of 5 MBq of 68Ga in a volume of 1-3 ml. Imaging of the brain using PET/CT Siemens Vision 600: 30 minutes after the administration of the tracer. For the first 3 patients, dual-day imaging with 68Ga and [68Ga]Ga-DOTA-SP will be performed to assess biodistribution: 5 MBq of 68Ga in a volume of 1-3 ml; 5 MBq of [68Ga]Ga-DOTA-SP in a volume of 1-3 ml. 4. Conducting the Therapy: Patients will be treated with a maximum of 6 cycles of [225Ac]Ac-DOTA-SP. Preparation of the Radiopharmaceutical: The labeling procedure will be carried out at the Nuclear Medicine Department at WUM. The radioisotope 68Ga is available at the Nuclear Medicine Department; the department has a registered 68Ge/68Ga generator. The team of radiopharmacists at the department possess the necessary qualifications and have been performing radiopharmaceutical labeling using 68Ga for many years. 225Ac will be supplied based on a cooperation agreement between WUM and the Institute for Transuranium Elements (Karlsruhe). After labeling, the prepared product will undergo quality control to verify the labeling efficiency and radiopharmaceutical purity. In any case, if the labeling efficiency is below 90%, the product will not be administered to the patient. Therapy: Administered activity of [225Ac]Ac-DOTA-SP - 20 MBq in a volume of 10-20% of the resection cavity volume, maximum amount of SP 200 μg (combined for 68Ga and 225Ac). - 20-30 minutes before administering [225Ac]Ac-DOTA-SP, 250 ml of 15% mannitol, 500 ml of 0.9% NaCl, and 8 mg of dexamethasone will be administered intravenously. - Immediately after administering the therapeutic dose of [225Ac]Ac-DOTA-SP along with 5-10 MBq of [68Ga]Ga-DOTA-SP, brain imaging will be performed; acquisition time 1-2 minutes. - Connection of an infusion pump with saline and administration at a rate of 0.5 ml/hour for 2-4 hours. - After the infusion, 2-4 hours after administering [225Ac]Ac-DOTA-SP, brain imaging will be performed with an acquisition time lasting 4-8 minutes, and a whole-body scan: acquisition time approx. 10 minutes. Radioisotope treatment will be carried out in the UCK hospital, during hospitalization at the Department of Neurosurgery. The length of hospitalization will depend on the patient's condition; from previous experiences, this has typically been 3 days. Previous experiences have shown good tolerance to treatment with [225Ac]Ac-DOTA-SP. The only noted side effects during therapy were transient facial flushing, and some patients experienced seizures (all patients had seizures noted before therapy as well). For this reason, patients will be hospitalized for 24 hours after therapy in the Department of Neurosurgery (UCK). However, in the case of poor tolerance to experimental treatment, it will not be continued. Additionally, steroid therapy will be initiated (if it had not been previously). In the event of a seizure, standard anticonvulsant treatment will be applied. Blood and urine tests will be performed 1, 2, 4, and 24 hours after administering [225Ac]Ac-DOTA-SP. Assessment of Distribution of [225Ac]Ac-DOTA-SP via SPECT/CT Imaging: - SPECT/CT imaging at two time points: 4 hours after the administration of the therapeutic radiopharmaceutical (after PET/CT imaging is complete) and 24 hours after its administration. - SPECT/CT imaging will follow a quantitative protocol developed at the Nuclear Medicine Department (UCK) based on phantom studies, including about 30 minutes of SPECT imaging using multiple energy windows and approximately 3 minutes of CT imaging at reduced exposure parameters, performed to locate the accumulation of the radiopharmaceutical and correct for radiation attenuation. - Before each subsequent administration and 2-4 weeks after administering [225Ac]Ac-DOTA-SP: Laboratory tests: Hematology, AST, ALT, Na, K, creatinine, urea, CRP, INR, D-dimers. Assessment of the Karnofsky Performance Status (KPS). Barthel Index assessment. Assessment of adverse effects. f. Observation: The patient should remain hospitalized at the Department of Neurosurgery (UCK) for 24 hours after treatment with [225Ac]Ac-DOTA-SP. Physical examination, neurological assessment, adverse events. 24 and 48 hours after the first administration of [225Ac]Ac-DOTA-SP. MRI with contrast will be performed every 2 months to evaluate treatment efficacy and +/- 2 weeks before each administration of [225Ac]Ac-DOTA-SP. Follow-up visits (including telemedicine options) will be conducted according to Good Clinical Practice and the therapeutic strategy used in the research center, every 2 months during the first 18 months or depending on the clinical status of the patient. After 18 months, scheduled follow-up visits (including telemedicine options) will take place every 3 months or more frequently if needed. g. Discontinuation of Therapy: The occurrence of serious adverse events (according to the definition related to TAT). Coexisting illness preventing further treatment. Progression of the lesion. In the case of the appearance of a new symptomatic solitary lesion in the MRI, treatment may continue at the researcher's discretion, provided that the initially treated lesion or area is stable or regressing. Withdrawal of the patient from the study. Changes in the patient's condition that, in the investigator's opinion, make further treatment impossible. The investigator may decide to withdraw the patient from the study for unforeseen reasons, ensuring their safety. . 5. Sample Size: The target sample size is 25 patients. Considering the possibility of patient dropouts, the group should include up to 35 patients. Patients will be recruited from those treated at the Departments of Neurosurgery (UCK, NIO). . 6. Study Endpoints: Primary: overall survival (OS) measured from the date of diagnosis. Secondary: time to progression (progression-free survival, PFS), defined as: 1. Clinical Progression: Clinical deterioration of performance status according to the Karnofsky scale or worsening of neurological function. The necessity of using or increasing the dose of corticosteroids by >50%. 2. Progression on MRI: Local progression within < 4 cm from the border of the primary lesion after resection or, A new lesion on MRI or, Progression of the lesion on MRI by > 25% between two consecutive imaging studies. In differential diagnostics, radiation necrosis should be included as a treatment-related effect (MRI perfusion and/or biopsy). - Expected Benefits of the Study: The expected outcome of the study is to assess the efficacy and safety of [225Ac]Ac-DOTA-SP with forced diffusion. It is anticipated that the proposed procedure should lead to an extension of survival time and time to disease progression compared to currently used therapeutic methods. . - Description of Risks and Discomforts for Study Participants: Based on current experiences with the treatment of [225Ac]Ac-DOTA-SP, no clinically significant side effects have been observed. The most frequently reported side effect was seizures (in all patients previously noted before therapy). No clinically significant side effects were identified in laboratory tests. There is no conclusive scientific evidence indicating that the administered local radioactivity poses a risk of developing cancer or hereditary defects. Current data suggest an extension of PFS and OS with the use of local treatment with [225Ac]Ac-DOTA-SP. . - Study Duration with Justification: The estimated duration of the study is 3 years. Patients who remain alive at the end of the study will be monitored until they report death. . - Biological Material: During reoperation and catheter placement, material will be collected for histopathological and genetic studies as per standard procedure. . - Patient Data Anonymization: No identifiable patient data will be stored alongside medical data subject to analysis. Patient medical data will be analyzed anonymously but will have an individual number corresponding to the anonymization list for each patient.
Phase
N/ASpan
156 weeksSponsor
Medical University of WarsawWarsaw
Recruiting
MEN1703 (SEL24) to Treat Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma (JASPIS-01)
The study consists of 3 parts, to investigate MEN1703 (Dapolsertib hydrochloride) in combination with glofitamab in patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) or MEN1703 alone in patients who have exhausted all standard treatment options (group 2). Part 1 (safety run-in) and Part 2 (enrichment): patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody (group 1) will receive either 150 mg or 125 mg of MEN1703 along with glofitamab. Patients who have exhausted all standard treatment options (group 2) will receive 125 mg of MEN1703 as a single-agent. Part 3 (optional randomized comparison): Patients who are naïve to treatment with an anti-CD3xCD20 bispecific antibody therapy will be randomized to receive either MEN1703 (Dapolsertib hydrochloride) at a dose selected from part 2 in combination with glofitamab or glofitamab alone.
Phase
2Span
108 weeksSponsor
Ryvu Therapeutics SAWarsaw
Recruiting
Magnesium Sulfate in Children Undergoing Laparoscopic Appendectomy
Pain in the perioperative period is associated with surgical stimuli but also with laryngoscopy and intubation. According to the currently applicable ERAS (Enhanced Recovery After Surgery) doctrine, the recommended method of anesthesia is multimodal, low-opioid anesthesia. The essence of multimodal anesthesia is to combine different methods (e.g. general and regional anesthesia) and various anesthetic drugs in order to reduce the intraoperative use of opioids. The one of commonly used co-analgetic is magnesium. The use of magnesium infusion before induction of anesthesia may enhance the analgesic effect of the opioid administered before intubation. In current guidelines for the relief of acute pain in children, magnesium sulfate may be considered as a coanalgesic. It is based only on expert consensus opinion and/or data from small studies, retrospective studies, registries. According to available data magnesium sulfate is superior to placebo in decreasing analgesic consumption and pain scores during the first 48 h after operation without any adverse effects in children with cerebral pals. In other groups of pediatric patients, the effectiveness of magnesium as a co-analgetic has not been proven. High quality randomized controlled trials are still missing. The primary outcome of this study is to assess opioid consumption during the laparoscopic appendectomy. Number of patients requiring rescue dose of opioids will be measured. The secondary aim is to examine total intraoperative fentanyl consumption, fluctuations of heart rate and blood pressure, metabolic, hormonal and inflammatory response (glucose, cortisol and IL-6 concentrations) and occurrence of side effects that may result from magnesium intake (decrease in blood pressure, bradycardia or allergic reaction). In the pediatric population, the optimal perioperative magnesium dosage is 50 mg/kg as a bolus followed by an infusion of 15 mg/kg/hour until the end of the operation. The general aim of the study is to evaluate the analgesic efficacy of intravenous magnesium sulfate as an adjunct to standard general anesthesia (involving intravenous induction and opioid with sevoflurane maintenance) for intubation and surgical trauma during anesthesia for laparoscopic appendectomy in children.
Phase
4Span
160 weeksSponsor
Medical University of WarsawWarsaw
Recruiting
A Study of Obexelimab in Patients With Systemic Lupus Erythematosus
This study consists of a 24-week treatment period followed by a 12-week follow-up period. Patients must have a clinical diagnosis of SLE at least 24 weeks prior to screening and meet the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria. To enter the Screening Period (Day -28 to Day -1) patients will have active SLE as defined by having: a) hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) ≥ 6 and clinical hSLEDAI ≥ 4, and b) British Isles Lupus Assessment Group (BILAG)-2004 Grade A or B in ≥ 1 organ system. Patients must be treated with one or more of the following background nonbiologic lupus standard of care therapies: oral corticosteroid, antimalarial, and/or immunosuppressant. On Day 1, patients will be randomized 1:1 to obexelimab or placebo subcutaneous (SC) injection once per week (QW) for 24 weeks. All patients will return to the study site for scheduled visits at Week 2, Week 4, and then every 4 weeks thereafter until study completion. During the study, patients will undergo assessments for efficacy, safety, PK, PD, and immunogenicity. Including screening and follow-up, the maximum duration of participation in this study for an individual patient is approximately 40 weeks (i.e., up to a 28-day Screening Period, 24-week Treatment Period, and a 12-week follow-up).
Phase
2Span
107 weeksSponsor
Zenas BioPharma (USA), LLCWarsaw, Mazowieckie
Recruiting
MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
Introduction RASopathies are a group of genetic diseases caused by mutations in the mitogen-activated kinase (RAS-MAPK) pathway. These mutations affect many processes and are the cause of numerous genetic syndromes (including Noonan syndrome) in the course of which severe hypertrophic cardiomyopathy (HCM) develops. MEK kinase inhibitors are used to treat cancers with mutations in the RAS-MAPK pathway in adults. So far, single cases of HCM treatment in patients with RASopathies have been described, with rapid improvement in both laboratory and echocardiographic parameters and regression of myocardial hypertrophy. Due to the described effectiveness, it is reasonable to verify these effects in a well-designed randomized study on a large group of patients. Objective To evaluate the effectiveness of trametinib treatment in patients with HCM and a genetic mutation in the RAS/MAPK pathway. Methodology Randomized, open-label study. The study will include patients aged 0 to 18 with: - mutation in the RAS/MAPK pathway confirmed by genetic tests - HCM diagnosed by echocardiography In the first phase of the study (3 months), patients will be randomly assigned to one of two groups: - the intervention group will receive trametinib and standard treatment (beta-blocker and disopyramide) - the control group will receive only standard treatment. Once this phase is complete, patients will be assessed. If higher effectiveness is demonstrated in the intervention group, in the second phase of the study, patients in the intervention group will continue their current treatment and patients in the control group will receive trametinib treatment. Each group will receive trametinib for 12 months. Importance of the study The study results will provide grounds for routine introduction of MEK kinase inhibitors for the treatment of patients with HCM due to RASopathy. If effectiveness is demonstrated, this group will gain a simple, non-invasive and causal treatment option.
Phase
2Span
122 weeksSponsor
Medical University of WarsawWarsaw
Recruiting
Evaluation of Maralixibat in Pruritus Associated With General Cholestatic Liver Disease (EXPAND)
This study will be conducted in multiple sites in North America, Europe, Middle East and South America.
Phase
3Span
124 weeksSponsor
Mirum Pharmaceuticals, Inc.Warsaw
Recruiting