Porto

Researchers are evaluating whether the Breathlessness diagnostics in a Box BiaB tool can shorten the time to diagnosis for patients experiencing breathlessness compared to usual care. This prospective, interventional study uses a stepped-wedge cluster design in general practice settings across the Netherlands, Spain, and Portugal. The main goal is to see if BiaB speeds up diagnosis, with secondary aims to identify more cases of chronic obstructive pulmonary disease COPD and cardiovascular disease CVD, and to assess the tools usability and efficiency. The study involves 45 general practice sites that start with a usual care period and sequentially transition to using the BiaB tool. Patients receive care as part of their regular visits, either through standard diagnostic procedures or with support from BiaB. No additional treatments are mandated by the study. Each site participates for 40 weeks, and data are gathered from routine clinical visits, electronic medical records, and questionnaires completed by patients and healthcare professionals. Participants attend a single study visit and may complete up to four quarterly questionnaires over a follow-up period lasting up to one year. Researchers measure the time from first presentation of breathlessness to diagnosis, the number of new COPD and CVD diagnoses, and the usability of the BiaB tool. Data are collected continuously during the usual care and intervention phases, allowing comparison of outcomes between these periods.

Researchers are studying the effects of elenestinib BLU-263 combined with symptom directed therapy SDT compared to placebo plus SDT in adults with indolent systemic mastocytosis ISM who have symptoms not well controlled by current treatments. This randomized, double-blind, placebo-controlled Phase 23 trial includes participants with ISM and smoldering systemic mastocytosis SSM, aiming to evaluate both safety and efficacy of the treatments. The study is sponsored by Blueprint Medicines Corporation and includes participants who have previously used selective KIT inhibitors as well as pharmacokinetic groups. Participants will be assigned to receive either elenestinib or placebo along with symptom directed therapies tailored individually. Elenestinib is taken orally once daily. The study is organized into multiple parts Parts 1 and 2 involve treatment periods lasting up to approximately 48 weeks, after which participants in Part 2 may continue into Part 3 and receive open-label elenestinib for up to five years. Part K enrolls those previously treated with KIT inhibitors. Symptom directed therapy doses are stabilized before treatment and maintained throughout. During the trial, participants will be monitored regularly for side effects and symptom changes using the ISM-Symptom Assessment Form ISM-SAF and other measures such as serum tryptase levels, KIT D816V allele fraction, bone marrow mast cell counts, and quality of life assessments. Safety will be tracked through adverse event reporting. The study duration can extend up to five years, allowing long-term evaluation of treatment effects and symptom control. Participants will have ongoing evaluations at set intervals including baseline, weeks 13, 24, 48, and beyond as applicable.

Researchers are studying the combination of 177LuLu-NeoB with ribociclib and fulvestrant in adults with advanced breast cancer that is estrogen receptor positive, HER2 negative, and gastrin releasing peptide receptor positive. This trial focuses on participants who have experienced early relapse after endocrine therapy or whose disease has progressed on endocrine therapy combined with a CDK46 inhibitor. The goal is to find the recommended dose of 177LuLu-NeoB when used with these other treatments. The trial consists of a dose escalation phase testing four planned doses of 177LuLu-NeoB 100, 150, 200, and 250 millicurie in small groups, followed by a backfill phase to gather additional safety and preliminary effectiveness data at an established dose. Participants receive 177LuLu-NeoB once every 28-day cycle for six cycles, along with daily ribociclib for the first 21 days of each cycle and fulvestrant on specific days starting from cycle 1 day 1. Pre- and perimenopausal women and men also get goserelin each cycle. Imaging with 68GaGa-NeoB is done during screening, possibly at cycle 2 day 15, and after treatment to assess disease. Participants attend clinic visits every 28 days for treatment, safety checks, and dosimetry assessments, with additional visits early in cycles 1, 2, 3, and 5. Tumor evaluations occur every 8 weeks up to 18 months, then every 12 weeks until 36 months, and further as needed. Safety follow-up lasts 8 weeks after treatment ends, followed by long-term monitoring every 12 to 24 weeks until 5 years from enrollment or until withdrawal, death, or loss to follow-up. Researchers measure dose-limiting toxicities, adverse events, dose changes, drug levels in blood, tumor responses, and survival outcomes.

Researchers are evaluating litifilimab BIIB059, a monoclonal antibody, in adults with active cutaneous lupus erythematosus CLE. This includes those with subacute or chronic CLE, with or without systemic lupus erythematosus SLE, who have not responded well or tolerated antimalarial treatments. The study aims to assess how litifilimab affects skin disease activity using scoring tools such as CLA-IGA-R and CLASI, as well as its safety and impact on quality of life. The study has two parts Part A and Part B. After screening, participants are randomly assigned to receive either litifilimab or a placebo injection under the skin every four weeks for 24 weeks in a double-blind setup. After this, all participants receive litifilimab for another 28 weeks. Those who finish may join a long-term extension study or enter a safety follow-up lasting up to 24 weeks. Treatment involves regular injections and monitoring during these periods. Participants will undergo assessments of skin symptoms, immune responses, and quality of life using questionnaires. Researchers will measure outcomes like the percentage of participants achieving low skin redness scores and significant reductions in skin disease activity. Safety monitoring continues through the study and follow-up, with total participation lasting up to 80 weeks.

Researchers are evaluating MDNA11, a long-acting beta-only recombinant interleukin-2 designed to activate immune cells that kill cancer while minimizing activation of immunosuppressive cells. This Phase 12 study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and early anti-tumor activity of MDNA11 alone or combined with the checkpoint inhibitor pembrolizumab in patients with advanced solid tumors. The study is conducted at multiple sites with regulatory and ethical approvals and includes about 115 patients. The trial has several parts dose escalation and expansion for MDNA11 monotherapy and for its combination with pembrolizumab. MDNA11 is given intravenously every two weeks with doses adjusted to find the recommended dose for expansion. Tumor assessments using CT or MRI scans happen every 8 weeks to monitor response until disease progression or other study-end criteria occur. Treatment may continue beyond progression under certain conditions. Participants undergo evaluations including tumor imaging, laboratory tests, and safety monitoring over up to 24 months. Researchers measure recommended dose levels, treatment-related adverse events, pharmacokinetics, immune response, and anti-tumor activity such as response rates and progression-free survival. Patients can withdraw anytime, and safety follow-up continues to understand MDNA11s effects alone and with pembrolizumab.

Researchers are evaluating an investigational drug called OHB-607 to prevent Bronchopulmonary Dysplasia BPD, a common chronic lung disease in extremely premature infants. The study compares infants receiving OHB-607 to those receiving standard neonatal care to see if the drug can reduce the incidence of severe BPD or death by 36 weeks postmenstrual age. This is a Phase 2b, randomized, open-label study involving infants born between 23 weeks 0 days and 27 weeks 6 days gestational age. Participants in the trial will be randomly assigned to one of two groups. One group will receive a continuous intravenous infusion of OHB-607 from birth until 29 weeks and 6 days postmenstrual age. The other group will receive standard neonatal care without the investigational drug. This approach allows researchers to compare the effects of OHB-607 against routine care practices for preventing lung disease in these infants. During the study, infants will be closely monitored through 36 weeks postmenstrual age and up to 24 months corrected age. Researchers will assess lung health, including the incidence and severity of BPD, time to weaning off respiratory support, and other complications such as intraventricular hemorrhage and retinopathy of prematurity. Developmental outcomes will also be measured using standardized scales at 24 months corrected age. Safety assessments and long-term follow-up are included to understand the drugs effects over time.

Researchers are studying if combining intismeran autogene with pembrolizumab can prevent advanced melanoma, a type of skin cancer that has spread and cannot be removed by surgery, from growing or spreading further. This study compares this combination to pembrolizumab with a placebo to see if patients live longer without their cancer worsening. The trial is a phase 2 randomized study designed to evaluate these treatments in people with advanced melanoma. Participants will be randomly assigned to receive either intismeran autogene via muscle injection every three weeks for up to nine doses plus pembrolizumab through an intravenous infusion every six weeks for up to 17 doses, or a placebo injection with the same pembrolizumab schedule. Treatment may continue for up to approximately two years or until the cancer progresses or the participant stops treatment. During the study, participants will be monitored with scans to measure tumor response and blood tests to assess safety and side effects. Researchers will measure how long patients live without their cancer progressing as the main outcome, along with response rates, duration of response, overall survival, and treatment-related adverse events. Participants may be involved in the study for up to about six years to fully assess these outcomes and monitor safety.

Researchers are investigating new treatments for high-risk, early-stage breast cancers that are either triple-negative or hormone receptor-low positive and HER2-negative. These types of breast cancer have limited amounts of certain proteins that affect growth, making them challenging to treat. This Phase 3 trial aims to compare the effects of adding sacituzumab tirumotecan, a targeted therapy, to pembrolizumab and chemotherapy against pembrolizumab with chemotherapy alone in controlling cancer growth and spread. Participants are randomly assigned to one of two treatment groups. One group receives sacituzumab tirumotecan intravenously every two weeks along with pembrolizumab every three weeks for 12 weeks, followed by pembrolizumab combined with carboplatin and paclitaxel for another 12 weeks. After this, surgery and optional radiation therapy occur, followed by pembrolizumab infusions for up to about 28 weeks. Additional treatments such as olaparib, capecitabine, or doxorubicin with cyclophosphamide may be given if cancer remains. The other group receives chemotherapy drugs carboplatin, paclitaxel, cyclophosphamide, and doxorubicin or epirubicin alongside pembrolizumab during similar time frames, followed by surgery, radiation, and pembrolizumab maintenance with possible additional treatments. Throughout the study, participants undergo assessments including surgery to remove tumors, imaging, and laboratory tests. Researchers measure cancer cell presence after surgery and monitor how long participants live without cancer progression or recurrence, as well as overall survival. Quality of life and side effects are tracked using questionnaires over several years. Safety is monitored by recording adverse events and treatment discontinuations. The study may last up to around 115 months for long-term follow-up.

Researchers are evaluating the safety, tolerability, and effectiveness of BNT113 combined with pembrolizumab compared to pembrolizumab alone as a first treatment for patients with unresectable recurrent or metastatic head and neck squamous cell carcinoma HNSCC that tests positive for human papillomavirus 16 HPV16 and expresses the protein PD-L1. This Phase IIIII trial includes patients whose tumors have a combined positive score of 1 or higher for PD-L1. The study is designed to generate important safety and efficacy data for these treatments in this patient group. The trial consists of two parts Part A is a non-randomized safety run-in phase to confirm the safety and tolerability of BNT113 with pembrolizumab. Part B is a randomized phase comparing BNT113 combined with pembrolizumab versus pembrolizumab alone. Treatments are given by intravenous injection or infusion. Patients may receive treatment for up to 24 months. An optional pre-screening phase allows tumor samples to be tested centrally for HPV16 DNA and PD-L1 expression before entering the main trial. Participants will undergo regular assessments including monitoring for treatment-emergent adverse events, overall survival, and progression-free survival for up to 48 months. Researchers will also measure response rates and duration, disease control, and any dose adjustments due to side effects. Patients provide tumor tissue samples before treatment and are monitored closely throughout the study period. The trial aims to collect comprehensive data on safety, treatment effects, and patient outcomes over this extended follow-up.

Researchers are evaluating rilvegostomig compared with pembrolizumab monotherapy as a first-line treatment for people with metastatic non-small cell lung cancer mNSCLC whose tumors have high PD-L1 expression. This Phase III, global, randomized, and double-blind study aims to assess the efficacy and safety of these treatments in this patient population. The trial is sponsored by AstraZeneca and focuses on patients with specific tumor characteristics and no certain genetic mutations. Participants will receive either rilvegostomig or pembrolizumab intravenously on Day 1 of each 21-day cycle. The study has two treatment arms one for the investigational drug rilvegostomig and one for the active comparator pembrolizumab. Both treatments are given as monotherapy to understand their effects as initial therapy in this cancer setting. During the study, participants will be monitored for overall survival and progression-free survival for up to approximately 5 years. Additional assessments include tumor response, duration of response, time to second progression or death, drug pharmacokinetics, immunogenicity, and patient-reported outcomes related to physical function, quality of life, and lung cancer symptoms. The study involves regular evaluations to track treatment effects and safety over an extended period.