L'île-perrot, Canada

A Phase IIIB Study to Evaluate the Use of Capivasertib in Combination With Fulvestrant in Patients With Advanced Breast Cancer Who Have Relapsed/Progressed on ET and CDK4/6 Inhibitor Reflecting Real World Clinical Practice in Spain

Phase IIIb, multicentre, single arm, Spain study assessing effectiveness/safety of capivasertib+fulvestrant in locally advanced (inoperable) or metastatic HR+/HER2- BC with the PIK3CA/AKT1/PTEN-altered following recurrence or progression on or after endocrine therapy and CDK4/6 inhibitor. Capivasertib will be administered as 400mg BD, 4 days on 3 days off in combination with fulvestrant at the approved dose of monthly 500mg (2 × 5mL IV), with an additional loading dose in Cycle 1.

Dimethyl Fumarate in Adrenomyeloneuropathy

Adrenoleukodystrophy (X-ALD) is the most prevalent rare genetic disorder affecting the brain's white matter. It is caused by mutations in the ABCD1 gene, which encodes a transporter involved in the degradation of very long-chain fatty acids (VLCFA). As a result, VLCFA accumulate in tissues and plasma, serving as a pathognomonic biomarker for diagnosis. The disease manifests in two main forms: i) adrenomyeloneuropathy (AMN), characterized by chronic progressive spastic paraplegia due to distal axonopathy, and ii) cerebral ALD (cALD), a rapidly progressing and fatal demyelinating leukodystrophy. Current therapeutic options are inadequate, limited to bone marrow transplants and gene therapy for patients with cerebral inflammation. No treatment is available for AMN, which affects 60% of patients. We have discovered that excess VLCFA leads to mitochondrial reactive oxygen species (ROS) production and oxidative damage, a major factor driving pathogenesis. More recently, we found that the main endogenous response to oxidative damage (the NRF-2 pathway) is impaired in X-ALD. Preclinical tests with an NRF2 activator, specifically the current treatment for multiple sclerosis, dimethyl fumarate (DMF/Tecfidera), showed promising results. All major molecular and cellular pathogenic mechanisms were restored, including: i) mitochondrial function and biogenesis, ii) redox homeostasis, iii) bioenergetic failure, iv) neuroinflammation, along with axonal damage and clinical signs of the disease such as locomotor disability. Consequently, we obtained an international patent for repurposing DMF for X-ALD (US15/957,601) and Orphan Drug Designation by the EMA in 2020 (EMA/OD/0000010028). Now we are translating this knowledge into a randomized phase IIb/III double-blind placebo-controlled study over 36 months for 40 AMN patients, to determine if DMF is effective in these patients. For the first 24 months, patients will be divided into two groups (placebo and active treatment) in a ratio of 1:2. A 12-month extension phase will follow, during which all patients will receive treatment. Furthermore, we aim to elucidate the molecular mechanisms driving the disease and dissect the redox-inflammatory effects of DMF using an integrative multi-omics approach, which will involve single-cell RNA sequencing in PBMC, and lipidomics in plasma. The clinical and molecular data from historical national and international AMN and cALD cohorts will be pooled to identify markers of severity and progression. Our goal is to address unmet needs in AMN while generating novel fundamental knowledge that will be useful for this and other common axonopathies.

Registry of Patients in Shock Treated With Vasopressin

The main objective is to characterise the routine clinical practice of vasopressin use in the context of shock in a multicentre observational study. By collecting clinical, analytical and echocardiographic data in a uniform manner, describing the time sequence of vasopressin and/or noradrenaline use; how long vasopressin is used; and which vasoconstrictor is more frequently withdrawn earlier: vasopressin or noradrenaline. The secondary objectives are: - to assess what motivated the decision to initiate AVP: type of shock, perfusion parameters, noradrenaline dose; - to define the impact of initiating AVP on noradrenaline dose (whether the dose can be reduced or not), on cardiac function (whether echocardiographic data improve or worsen) and on perfusion data (whether laboratory and clinical data such as lactate, capillary refill time, mottling score or diuresis improve or worsen); - estimate what is the dose range of AVP used and what is the maximum dose used in routine clinical practice; - observe when AVP is stopped, how (abruptly or progressively); - describe the incidence of side effects of AVP, whether it is related to the dose of AVP and the comorbidities of the patients; - assess medium/long-term outcomes: 28- and 90-day mortality, ICU and hospital stay, days of vasopressor support, days of mechanical ventilation, days of renal replacement.

Study of ATX-01 in Participants with DM1

Selinexor Plus Gemcitabine in Selected Advanced Soft-tissue Sarcoma (SeliSarc)

Phase I-II, non-randomized, single-arm, open-label, multicenter, international clinical trial. Patients with advanced soft-tissue sarcoma (leiomyosarcoma or malignant peripheral nerve sheath tumor) will receive selinexor in combination with gemcitabine. In the Phase I part safety and toxicity of the combination will be assessed using a 3+3 design. The recommended dose for the Phase II will be determined. In the Phase II part there will be 2 different cohorts: Cohort 1: Leiomyosarcoma (LMS) Cohort 2: Malignant peripheral nerve sheath tumor (MPNST)

A Study to Evaluate the Effects of ACI-7104.056 Vaccination in Patients With Early Stages of Parkinson's Disease

This is a prospective, multicenter, placebo-controlled, double-blind, randomized study with adaptive features, comprising a screening period of up to 8 weeks, a 74-week double-blind treatment period, and a 26-week post-treatment follow-up period. Up to 3 cohorts will include 16 subjects each (12 under the study vaccine and 4 under placebo; 3:1 active treatment/placebo ratio). One of the initial potential 3 cohorts (Cohorts 2 and 3 are optional) may be expanded in order to reach an overall total of up to 150 subjects in the study. In case a cohort is expanded, the randomization ratio will be adjusted to achieve an active treatment/placebo ratio of 2:1 in this cohort. The route of administration of the study vaccine and placebo will be by intramuscular injections.

Prospective, Single-Arm, Multicenter Study to Evaluate the Effectiveness and Safety of Endovascular Treatment in Patients With Cerebral Aneurysms Using P64 and P48 Flow-Diverter Stents

The goal of this study is to evaluate the effectiveness and safety of endovascular treatment for cerebral aneurysms using the flow-diverting stents p64MW (flow modulation device) HPC and p48MW HPC in the routine clinical practice of several Spanish hospitals. It is therefore an observational study, carried out with devices already commercialized. The success rate of the intervention, the rate of hemorrhagic and thromboembolic complications, as well as variables related to the clinical and radiological follow-up of patients over a 12-month period, will be analyzed.

Prospective Study for the Outpatient Treatment of Patients With Very Low Risk Acute Symptomatic Pulmonary Embolism.

Pro-Vegetarian Diets, Microbial/Metabolite Profiles and Cancer

Plant-based foods (fruits, vegetables, cereals, nuts and seeds, legumes, and vegetable oils) are the main source of fiber and other bioactive compounds in the diet. Plant-based diets are therefore assumed to prevent mortality and the ocurrence of chronic diseases including cancer. However, evidence on this issue is still scarce, and the mechanisms and drivers of their potential health benefits are also only partially known. The main objectices of this project are: 1. To develop and validate dietary assessment methods for the vegetarian population 2. To assess dietary habits and consumer beliefs of vegetarians with respect to omnivores, considering different types of vegetarian diets 3. To identify a gut microbiota signature related to plant-based diets from subgroups of subjects following a plant-based diet foods (vegans, lacto-vegetarians, …, and pro-vegetarians) and omnivorous subjects (non-plant-based diets), from stool metagenomic sequencing. 4. To relate this signature with metabolites present in faeces (related to the presence of certain microbial species) and in urine to improve the predictive capacity of the microbial signature of vegetable diets. 5. Validate the signature using independent study populations, and including colorectal and breast cancer survivors as another study target.

FB-CT2 Includes Two Prospective, Multi-centre Studies With a Medical Device in Hospital Settings: a Randomized, Dual-arm, Open-label Pilot Study in Spain, Followed by a Single-arm, Non-randomized, Open-label International Pivotal Study

The study titled "Evaluation of the safety and the preterm birth predictive capacity of the clinical investigation device 'Cervisense TPTL': an international clinical study" is designed to assess both the safety and performance of the Cervisense TPTL device in predicting spontaneous preterm birth. It is being conducted across various Gynaecology, Obstetrics, and Emergency Services in hospitals throughout Spain and Germany. Cervisense TPTL is the investigational product being evaluated. It includes two components: the Cervisense Intravaginal Probe V0.1, which measures cervical stiffness, and the Fine Birth algorithm, which combines the measurement with clinical data to assess the short-term risk of spontaneous preterm labor. The device is intended for use in pregnant women showing symptoms of threatened preterm labor (TPTL), with intact amniotic membranes and a single fetus, between 28 weeks and 36 weeks plus 6 days of gestation. Its purpose is to determine the risk of spontaneous preterm birth within the following 7 days. The clinical investigation is structured in two phases. The pilot study is a randomized, dual-arm, open-label, interventional, multi-centre study conducted in Spain. Participants are randomized 1:1 to receive either the standard of care or the Cervisense evaluation. The pivotal study is non-randomized and single-arm, also open-label and interventional, conducted at a larger scale across multiple centres in both Spain and Germany. The main goal is to confirm that the device is safe to use and reliable in clinical settings. For safety, all adverse events associated with the use of the device are documented and analyzed in terms of severity, duration, and required intervention. Special attention is given to potential complications such as tissue trauma or infection. To ensure unbiased evaluation, a Clinical Events Committee and a Data Safety Monitoring Board have been established to independently review adverse events and guide study continuation. Inclusion Criteria: - Female ≥18 years - Singleton pregnancy - Live fetus, 28w+0d-36w+6d GA - Intact membranes - Cervical dilatation <2 cm - Signed informed consent - Regular uterine contractions (≥8/60 min) (Pivotal only) Exclusion Criteria: - Latex allergy - Prolapsed membranes - Fetal malformation - Fetal infection - Vaginal bleeding (severe or persistent) - Cervical cerclage - Müllerian anomalies - Pessary use - Regular uterine contractions (reported by patient) (Pilot only) - History of preterm birth or TPTL (Pilot only) - Vasa/placenta previa (Pilot only) - Gastrointestinal or urinary infections (Pivotal only)