Lisboa

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.

This research aims to evaluate how full-arch implant-supported prostheses affect lip support in patients undergoing complex dental rehabilitation. The study focuses on how different clinical and laboratory decisions between diagnosis and prosthesis delivery may influence the prosthetic design and the patients facial profile. Advanced 3D facial scanning and superimposition techniques allow precise measurement of vertical occlusion and lip support. Participants will undergo removal of their full-arch implant-supported prostheses, with digital facial images captured before and after this procedure using a facial scanner. This observational study leverages modern digital technology to measure changes objectively and does not involve experimental treatments. During the study, researchers will assess changes in the volume around the mouth area, distances between the lips and esthetic lines on the facial profile, and angles related to the nose and lips. These measurements occur on the same day as the prosthesis removal. The study helps improve understanding of facial changes related to dental prostheses and involves participants collaborating with the research protocol through imaging and clinical assessments.

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 evaluating MammoWave, a device that uses low-power microwaves instead of X-rays, for early breast cancer detection in women aged 45 to 74. This prospective, multicenter clinical investigation aims to confirm that MammoWave achieves sensitivity greater than 75 and specificity greater than 90 for breast cancer detection among 10,000 volunteers undergoing regular screening programs. The study compares MammoWave results with conventional breast examination methods including mammograms and other radiological or histological tests. Participants will undergo both the standard breast screening exams and the MammoWave exam. The MammoWave exam involves lying prone on a bed while the device collects microwave data from both breasts over about 8 minutes. Data processing uses a special imaging algorithm to produce microwave images and classification results indicating suspicious or non-suspicious findings. The study device contains the same hardware as a CE-marked version but uses updated software. During the study, participants will have conventional breast exams along with the MammoWave exam. Researchers will evaluate MammoWaves sensitivity and specificity during the procedure and analyze detection rates, recall rates, and positive predictive values at baseline. Volunteers will also complete satisfaction questionnaires. The study will monitor breast cancer detection by histological type, size, and breast density. The trial is expected to run until December 2026.

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 investigating new treatments for Pulmonary Arterial Hypertension PAH, a condition where the blood vessels in the lungs thicken and narrow, causing high blood pressure in the lungs and making it difficult for the heart to work properly. PAH can lead to breathing difficulties and reduced activity levels. While current treatments help manage symptoms, they do not stop the disease from progressing. Sotatercept is a study medicine designed to target specific proteins involved in PAH, and this long-term follow-up study aims to assess its safety and tolerability when used alongside standard PAH treatments over an extended period. Participants who have completed previous sotatercept PAH studies may join this open-label follow-up study. Those from blinded studies will start sotatercept at 0.3 mgkg by subcutaneous injection every three weeks and may increase to 0.7 mgkg. Participants from unblinded studies will continue their current dose and may also increase to 0.7 mgkg. The study focuses on monitoring sotatercept use combined with background PAH therapy to observe long-term effects. Throughout the study, participants will undergo regular assessments including tracking adverse events, laboratory tests for blood and chemistry markers, body weight, blood pressure, and electrocardiograms up to approximately 7 years. Additional measurements include walking distance tests, heart function markers, and risk scores related to PAH. Safety monitoring and tolerance to the medication will be closely observed over time to better understand sotatercepts long-term impact in managing PAH.

Researchers are evaluating the efficacy, safety, and tolerability of subcutaneous ianalumab in adults with diffuse cutaneous systemic sclerosis, a serious autoimmune condition. This Phase 2 study compares ianalumab against a placebo to better understand its effects on this disease. The study is sponsored by Novartis Pharmaceuticals and aims to assess how ianalumab impacts disease activity and progression. The study includes multiple periods a screening period lasting up to 6 weeks a first treatment period of 52 weeks where participants receive either ianalumab or placebo injections followed by a second open-label treatment period of an additional 52 weeks where all participants receive ianalumab. After treatment, there is a post-treatment follow-up period lasting at least 20 weeks and up to 2 years to monitor long-term effects. Participants will undergo regular assessments including measuring their response using the 35 rCRISS25 scale at Week 52, lung function changes, skin thickness scores, and physical disability indexes. Blood samples will be collected throughout the study to monitor drug levels and antibodies. Safety is closely monitored by recording any adverse events during the entire study duration, which can last up to 208 weeks. The study involves detailed clinical evaluations and laboratory tests to fully assess the impact of ianalumab on this condition.