Uppsala

Researchers are evaluating the safety and effectiveness of elenestinib (BLU-263) combined with symptom-directed therapy (SDT) compared to placebo plus SDT in people with indolent systemic mastocytosis (ISM) whose symptoms are not well controlled by SDT alone. This Phase 2/3 randomized, double-blind, placebo-controlled study includes participants with ISM and smoldering systemic mastocytosis, and also involves groups for pharmacokinetic studies and participants who previously received a selective KIT inhibitor. The study is divided into multiple parts. Parts 1 and 2 enroll participants with ISM who will receive either elenestinib oral tablets or placebo alongside their symptom-directed therapy. Participants from Part 2 may continue into Part 3, which is an open-label extension where all receive elenestinib. Part K enrolls participants with ISM who have prior experience with selective KIT inhibitors. The study tracks treatment effects and safety over time. Participants will be monitored for up to 5 years, with assessments including the number of treatment-emergent adverse events, changes in symptom scores measured by the ISM-Symptom in Assessment Form, and overall safety monitoring. Evaluations occur at baseline, 13 weeks, 49 weeks, and throughout the long-term follow-up. The study also includes detailed tracking of symptom control and adverse events to evaluate the impact of treatment on participants' health and quality of life.

Researchers are evaluating the safety and effectiveness of rilzabrutinib compared to placebo in adults with active Immunoglobulin G4 Related Disease (IgG4-RD). This Phase 3, randomized, double-blind study aims to measure the time until the first IgG4-RD clinical disease flare during a 52-week treatment period. Additional goals include assessing disease control, flare-free rates, use of glucocorticoid rescue, and monitoring safety through adverse events, laboratory tests, and electrocardiograms. Participants will be randomly assigned to receive either oral rilzabrutinib tablets or placebo for 52 weeks. Glucocorticoids may be used as rescue medication if needed. The study includes a screening period lasting 4 to 6 weeks before treatment begins, followed by the 52-week double-blind treatment phase, and a 2-week follow-up after treatment. An optional open-label extension lasting up to 108 weeks is also available for participants. During the study, participants will attend 16 visits for assessments, which may include clinical evaluations, imaging tests such as CT, MRI, PET, or ultrasound to monitor disease activity, and laboratory tests. Researchers will track time to disease flare and collect data on flare-free rates, safety parameters, and medication use. Participants' vaccination status and contraceptive use will be monitored according to local guidelines, and overall study participation could last up to 60 weeks or longer if joining the extension phase.

Researchers are investigating new treatments for people with high-risk, early-stage breast cancer, specifically targeting triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/HER2-negative breast cancer. These types have little or no HER2 protein and involve hormones like estrogen or progesterone. The study aims to evaluate if the addition of sacituzumab tirumotecan (sac-TMT), a targeted therapy, combined with pembrolizumab and chemotherapy can improve outcomes compared to pembrolizumab with chemotherapy alone. Participants receive treatments including sacituzumab tirumotecan, pembrolizumab, and chemotherapy drugs such as carboplatin and paclitaxel, all given by intravenous infusion. Rescue medications like antihistamines, acetaminophen, dexamethasone, or steroid mouthwash may be used as needed. The study is randomized and open-label, comparing sac-TMT followed by chemotherapy plus pembrolizumab to chemotherapy and pembrolizumab without sac-TMT. During the study, researchers will monitor participants up to about 30 weeks to assess the percentage of people with no remaining cancer cells at surgery. They will also follow participants for up to approximately 92 months to track event-free survival, meaning time without cancer growth, spread, or return. Participants will undergo imaging, clinical assessments, and laboratory tests to evaluate treatment effects and safety throughout the study.

Researchers are conducting a first-in-human, open-label, phase 1 trial to evaluate the safety, tolerability, and distribution of a drug called [177Lu]Lu-ABY-271 in patients with HER2-positive metastatic breast cancer. This trial involves subjects with advanced, unresectable breast cancer that overexpresses the HER2 protein, and aims to study how the drug behaves in tumors and critical organs. The trial has two parts: Part A will enroll up to 6 subjects sequentially to study the uptake of [177Lu]Lu-ABY-271 in tumors and organs. In Part B, 15 subjects will be randomized into three groups receiving different protein mass doses of the drug, divided into two cohorts with varying radioactivity levels, to determine the best dosing for future trials. Each participant receives a single infusion of [177Lu]Lu-ABY-271. Participants will be monitored from baseline through to the end of the trial, which is Day 29 for Part A and Day 43 for Part B. Researchers will assess treatment-emergent adverse events and dose-limiting toxicities during this period. Subjects will undergo evaluations to measure drug biodistribution and safety, including tumor response and any side effects related to treatment.

Researchers are conducting a first-in-human phase 1 trial to study OX118, a human monoclonal antibody targeting OX40 ligand, in healthy adult volunteers aged 18 to 60 years. The study aims to assess the safety, tolerability, and pharmacokinetics of OX118 when given as a single intravenous dose. A total of 32 healthy men and women with a body mass index between 18.5 and 30.0 will participate in this trial. Participants will be divided into five groups receiving increasing doses of OX118 or placebo, ranging from 0.1 mg/kg to 10 mg/kg. Each group includes a mix of participants receiving the drug or placebo by intravenous infusion according to a set schedule. The study spans approximately 91 days per participant, including up to 28 days for screening and 7 clinic visits, with the treatment visit involving a 24-hour stay for close monitoring. Dosing follows a sentinel plan for safety, and an internal safety review committee evaluates data before advancing to the next dose group. During the study, participants will undergo assessments including adverse event monitoring, vital signs, ECGs, lab tests, physical exams, and medication reviews. Safety and tolerability data are collected from day 1 through day 63. Researchers will carefully observe participants for any abnormal signs or reactions. Follow-up visits confirm ongoing safety, and participants are monitored closely by medical staff throughout their involvement to ensure well-being and adherence to trial procedures.

Researchers are evaluating the long-term safety and effects of nerandomilast in people with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) who have previously completed treatment with nerandomilast in earlier studies. The study aims to understand how well participants tolerate nerandomilast over time, and whether it helps improve lung function, delays symptom worsening, reduces hospital visits, or impacts survival. This is a Phase 3 open-label extension trial. Participants take nerandomilast tablets daily for up to 1 year and 10 months while continuing their usual pulmonary fibrosis treatments. The study follows an open-label design where all participants receive nerandomilast. There are no placebo or comparator groups in this extension phase. Throughout the study, participants regularly visit their doctors for health assessments and lung function tests. Doctors monitor any health problems or side effects experienced during treatment. The main outcome measured is whether participants experience any adverse events up to the final follow-up visit, which occurs at week 99. This close monitoring helps evaluate the long-term safety and potential benefits of nerandomilast in this patient group.

This is a long-term follow-up trial to the post-authorisation efficacy and safety (PAES) trial (trial 20-HMedIdeS-19). The trial will include patients who participated in the PAES trial and were transplanted with a new kidney after treatment with imlifidase (trial drug) or standard of care medication. Imlifidase is a medicine used to prevent the body from rejecting a newly transplanted kidney and is used before transplantation in adults who have antibodies against the donor kidney and are considered 'highly sensitised' based on a positive crossmatch test. The purpose of this follow-up trial is to fulfil requirements from the European Medicines Agency (EMA) to continue to evaluate efficacy (kidney function) and safety (side effects) over time, for the patients who were transplanted with a new kidney in the PAES trial. The patients will be followed for up to 5 years after transplantation in the PAES trial to collect valuable long-term data.

BACKGROUND, AIMS AND HYPOTHESES Eating disorders (EDs) are psychiatric conditions characterized by a loss of control over food intake. The prevalence of anorexia nervosa (AN) is estimated at approximately 1-2%, while bulimia nervosa (BN) affects 2-3% of the population. EDs significantly impair functioning, have serious health consequences, and are associated with high mortality rates. Around 20% of patients with AN and 10% of those with BN develop a long-lasting illness, often referred to as Severe and Enduring Eating Disorders (SEED). While there is no scientific consensus on the definition of SEED, it is frequently defined as a duration of illness lasting seven years or more. Research suggests that factors maintaining EDs may differ from those that trigger them. The underlying causes of EDs remain largely unknown, though their origins are considered multifactorial. Psychiatric comorbidities are highly prevalent in EDs, significantly influencing their course and outcomes. Personality disorders (PDs) are associated with poorer treatment outcomes for EDs, but longitudinal studies examining the trajectory of PDs in EDs are limited, and findings are inconsistent. Dysfunctional emotion regulation (ER) has been identified as a transdiagnostic psychological risk factor for many psychiatric disorders, including EDs. ER difficulties can manifest as undercontrol, characterized by personality traits such as impulsivity and insufficient self-control, or overcontrol, characterized by emotional inhibition and excessive self-control och cognitive inflexibility. Some models propose that undercontrol is central to BN, while overcontrol are core features of AN. However, the course and stability of ER in EDs remain poorly understood due to a lack of longitudinal studies. Another understudied factor in EDs is loneliness, encompassing perceived social isolation and a lack of connectedness. Loneliness has been linked to ER strategies, such as excessive self-control and emotional avoidance, which in youth can contribute to social isolation, reduced life satisfaction, and a higher risk of enduring mental health problems. The role of loneliness in SEED, however, is not well understood. Further, research on EDs has proposed that biological factors, including dysregulation of the immune system, plays a role in the development and maintenance of the EDs. Studies indicate a pro-inflammatory state in AN, though it remains unclear whether this is a state or trait marker. The role of inflammation in BN is even less understood, and studies present mixed findings. Some evidence suggests an increased risk of BN in individuals with autoimmune or inflammatory diseases, highlighting the need for further investigation into inflammatory markers over the course of the illness. In summary, clinical factors such as psychiatric comorbidity and personality disorders; psychological factors including personality characteristics, dysfunctional emotion regulation, overcontrol/undercontrol, cognitive inflexibility, loneliness, and severe eating disorder (ED) symptoms; and biological factors such as immune system dysregulation may all play a role in the development, maintenance, and relapse of EDs. However, research in this field is scarce. This projects aims is to increase our knowledge about risk factors for a severe course in EDs. Our overarching research question is: What are the key clinical, psychological, and biological risk factors of a severe and enduring course of an eating disorder? It is hypothesized that a chronic course of ED is related to severe ED symptoms, personality traits related to maladaptive over- and undercontrol, difficulties with emotion regulation (ER), and increased systemic inflammation. Primary outcomes are * eating disorder diagnosis at follow-up * severity of eating disorder symptoms Secondary outcomes are * psychosocial impairment * quality of life * loneliness at follow-up * comorbidity at follow-up * systemic inflammatory activity at follow-up * Physical status at follow-up Predictors, moderators and mediators * emotion regulation * personality * cognitive flexibility * loneliness at baseline * comorbidity at baseline * systemic inflammatory activity at baseline * duration of illness * time in treatment * motivation for change * treatment completion/treatment dropout * Physical status at baseline PROCEDURE Two prospective cohorts of patients with eating disorders (EDs)-one adolescent and one adult-will be followed longitudinally to examine changes in and the impact of clinical factors, personality traits, emotion regulation (ER) difficulties, loneliness, and biomarkers. Data will be collected at baseline, post-treatment, two years post-baseline, and at five, 10, and 20 years. Participants will be recruited consecutively from autumn 2024 onwards from the Eating Disorder Unit at the Uppsala Department of Child and Adolescent Psychiatry (ED-CAP) and the eating disorder unit for adults (ED-P). Child and adolescent psychiatry (ED-CAP) The eating disorder unit at the Department of Child and Adolescent Psychiatry at Uppsala University Hospital (CAP) treats patients with AN, BN, Other Specified Feeding or Eating Disorder (OSFED), and Avoidant Restrictive Food Intake Disorder (ARFID) up to 18 years. Patients are referred to the unit either by other healthcare professionals or by themselves and/or their parents. All patients are systematically assessed using a structure implemented by Swedish ED clinics that provides valid data to the national quality register. The structure consists of an assessment of clinical history, diagnostic evaluation with the child and adolescent version of the MINI International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) or Electronic Psychiatric Screening Interview for children (EPSI-C), the Eating Disorder Examination interview (EDE-I), and clinician rating of symptoms and functioning (C-GAS) and the Clinical Global Impressions scale (CGI). In addition, weight and height are measured, and self-ratings with the Eating Disorder Examination Questionnaire (EDE-Q), Clinical Impairment Assessment Questionnaire (CIA), and Montgomery-Åsberg Depression Rating Scale Self-Assessment (MADRS-S) are collected. After this initial assessment, all patients will be invited to participate in research. A research nurse will invite all patients and perform the initial somatic examination as well as sampling of blood. The patients who accept participation will sign informed consent to be included in the study. Since the youths are at least 14 years old, their parents/caregivers will also be required to accept participation and sign informed consent. Participants will receive questionnaires sent to them digitally. The eating disorder clinic for adults (ED-P) The eating disorder clinic for adults at the Department of Psychiatry at Uppsala University Hospital (ED-P) treats adults (≥ 18 years) with EDs. The clinic receives referrals from healthcare professionals (mainly physicians or psychologists) from other parts of the regional healthcare system. Patients can also refer themselves. All patients undergo a systematic evaluation upon arrival at the eating disorder clinic. This consists of a clinical history and a structured diagnostic interview; either the MINI for DSM-5 or the Structured Clinical Interview for DSM-5 Axis I Disorders - Clinical Version (SCID-I CV). Patients also undergo the Eating Disorder Examination interview (EDE-I) and complete the self-report instruments Eating Disorder Examination Questionnaire (EDE-Q), Clinical Impairment Assessment Questionnaire (CIA), and Montgomery-Åsberg Depression Rating Scale Self-assessment (MADRS-S). Weight and height are measured. All diagnostic assessments at the Department of Psychiatry are conducted by psychologists or physicians who have received training in the procedure. Patients who, during the assessment, are diagnosed with AN, BN, BED, ARFID, or OSFED of moderate to severe intensity, or OSFED with psychiatric comorbidity, and who accept treatment are accepted for treatment at P-ED. Patients who are diagnosed with mild OSFED or moderate OSFED without psychiatric comorbidity are referred to primary care for monitoring or treatment. After this initial assessment, all patients will be invited to participate in research. An appointed person will invite all patients. If the patient accepts participation, they will sign an informed consent form. Participants will receive questionnaires sent to them digitally. All Ages: Both ED-CAP and ED-P Participants will be asked about the collection of biomarkers through Uppsala Psychiatric Patient samples (UPP) (ethics approval Dnr 2012/081), which is an infrastructure for the collection of biological materials at the Department of Psychiatry at Uppsala University Hospital. All patients will be invited to participate in UPP, and inflammatory markers will be analyzed in accordance with the informed consent for UPP. Inflammatory markers will be analyzed from venous blood samples drawn from participants before treatment, immediately after treatment or dropout, and at the two-year follow-up. At baseline, the following data will be collected: Diagnoses, physical examination (BMI, pulse, blood pressure), demographic characteristics, clinical characteristics, personality traits, psychological risk factors (e.g., ER difficulties, including loneliness), and biomarkers (including markers of inflammation). The same procedure will be repeated again after two years. A few questionnaires will be distributed at treatment termination or dropout. After five, 10, and 20 years, patients will be followed up through National Helath registers and with questionnaires. Weighing will be performed weekly during treatment and at the follow-up two years later. At all time points, questionnaires will be distributed digitally. Process measures, such as the type of received treatment, number of treatment sessions, whether the patient dropped out or completed treatment, will be monitored. At follow-up, participants will be asked to answer a set of questions regarding, for example, living conditions, in addition to the questionnaires assessed at baseline. QUALITY ASSURANCE PLAN Interviewers will be trained and quality assured by calculating inter-rater agreement. For self-assessment, well established psychometrically evaluated instruments have been chosen. Special consideration has been given to selecting instruments suitable for both adolescents and adults. SAMPLE SIZE ASSESSMENT Sample size calculations were performed to ensure adequate power for the proposed analyses. With a Cohens effect size of d = 0.2, 199 participants will be required in each group, given an alpha of 0.05 and a power of 0.8. Dropout over time is expected, which increases as more time passes, estimating a 50% dropout by the final physical follow-up. Therefore, just under 400 participants need to be included in each group in order to have sufficient data for the last follow-up. DATA ANALYSES A range of statistical techniques will be employed to address the hypotheses and research aims, considering the longitudinal design, comparisons between the adolescent and adult cohorts, and diversity of outcome variables: Descriptive analyses - Descriptive statistics (means, standard deviations, proportions) will summarize demographic, clinical, psychological, and biological variables at baseline and follow-up. Correlation analyses will explore relationships between predictors and primary and secondary outcomes. Comparisons between subgroups * Cluster analyses will be performed to identify subgroups of participants with different profiles of personality traits. These cluster will be compared regarding predictors, mediators/moderators, secondary outcomes, and primary outcomes. * Between-group comparisons will also be conducted using t-tests, ANOVA or nonparametric alternatives (e.g., Mann-Whitney U tests) with regard to predictors and outcomes. Longitudinal Regression Analyses * Linear Mixed-Effects Models (LMM): These will evaluate changes in continuous outcomes over time. * Generalized Estimating Equations (GEE): These models will analyze categorical outcomes, accounting for repeated measures and within-subject correlations. * Logistic Regression: Logistic models will predict binary outcomes at follow-up. Mediation and Moderation Analyses * Mediation Analysis: mediation models will assess how variables mediate the relationship between predictors and primary and secondary outcomes. * Moderation Analysis: Moderation models will explore how variables influence the relationship between predictors and primary and secondary outcomes. Survival Analysis \- Cox proportional hazards models will be used to analyze time-to-event data, such as time to dropout and relapse. Inflammatory Biomarker Analyses \- Levels of inflammatory markers in the ED samples will be compared to samples from individuals with other psychiatric disorders, as well as with healthy controls. Since blood samples will be taken upon repeated times during the study period, comparison of levels of inflammatory markers during disease course will be possible. Missing data will be addressed as instructed for each instrument, ur by using multiple imputation or mixed-model approaches. Subgroup Analyses \- Separate analyses will be conducted for adolescent and adult cohorts to examine potential differences in predictors and outcomes. All statistical analyses will be performed using appropriate software (R, SPSS), and sensitivity analyses will be conducted to assess the robustness of findings.

Researchers are evaluating the binding of a new PET tracer called [68Ga]Ga-DOTA-Cys-ATH001 in the liver and gastrointestinal tract among healthy volunteers and patients with metabolically caused steatohepatitis (MASH), fibrostenotic Crohn's Disease (CD), and primary sclerosing cholangitis (PSC). This first-in-human, phase 0 trial aims to compare tracer uptake across these groups and assess the tracer's safety and distribution in the body. Participants receive one intravenous dose of up to 100 micrograms of [68Ga]Ga-DOTA-Cys-ATH001, followed by whole-body PET and MRI scans to visualize tracer binding and body function. Some participants will have longer PET scans to study tracer clearance and biodistribution, and a subgroup will return for a second dose and imaging to assess test-retest reliability. Blood samples are taken in select cohorts to measure tracer levels over time. Before dosing, participants undergo health and eligibility checks including FibroScan® for certain groups. Safety tests such as vital signs, ECG, and laboratory samples are done after imaging. A remote follow-up call occurs the next day to monitor any side effects or injection site reactions. The total participation includes screening, one or two imaging visits, and follow-up, with visits spaced up to six weeks apart for some subgroups.

Researchers are studying head and neck squamous cell carcinoma (HNSCC) patients with factors that increase the risk of treatment failure. The goal is to personalize treatment and improve outcomes for those receiving curative radiotherapy. This phase III trial compares the standard radiation dose to a higher dose given more frequently (hyperfractionated radiotherapy) to see if intensifying treatment benefits patients with advanced disease. The study also explores advanced imaging and genetic tests to better predict treatment response and cancer behavior. Participants will be randomly assigned to receive either the standard radiotherapy dose of 68.0 Gy in 34 fractions once daily or a higher hyperfractionated dose of 83.0 Gy in 68 fractions given twice daily over five days a week. Different radiation doses are targeted to the primary tumor and affected lymph nodes based on risk areas. The trial includes translational research using MRI, CT, and PET scans, as well as gene and protein analyses, to understand tumor characteristics and treatment effects. Patients with lower-risk tumors not eligible for randomization can still join the research parts that do not involve altered radiation schedules. During the study, participants will undergo regular monitoring including imaging and clinical assessments every three months for two years, then every six months up to five years to check local tumor control. Researchers will collect data from these visits along with tissue and blood samples for genetic and immune profiling. Safety, treatment adherence, and long-term outcomes will be closely followed to evaluate the impact of the different radiotherapy approaches and the predictive value of the biological tests.