Clinical Research Directory

Phase 2/3 Study of KPL-387 in Recurrent Pericarditis

This study is being done to demonstrate whether KPL-387 is an effective and safe treatment for recurrent pericarditis.

CACP: Study on Camptodactyly - Arthropathy - Coxa Vara - Pericarditis (CACP) Syndrome

CACP syndrome is a rare autosomal recessive disorder characterized by the triad of camptodactyly, non-inflammatory arthropathy with synovial hyperplasia, and coxa vara. Occasionally, non-inflammatory pericarditis and pleural effusion may also occur. This syndrome is likely underdiagnosed due to its rarity. Epidemiological information is limited to isolated case reports or small patient series, with the largest reported cohort including 35 patients. The genetic cause of CACP syndrome is associated with mutations in the PRG4 gene, located on chromosome 1q31.1. While clinical signs (camptodactyly, non-inflammatory arthropathy, and coxa vara) and radiological findings suggest the diagnosis, genetic testing confirms it by identifying pathogenic biallelic mutations in PRG4. To date, twenty-two mutations have been identified, all leading to premature stop codons and the absence of functional lubricin. However, the exact pathophysiology of CACP syndrome remains incompletely understood. Clinical manifestations of CACP syndrome can vary, even within the same family. The progressive and slow onset can initially present as an incomplete clinical picture. However, camptodactyly (85- 100%) and arthropathy (100%) are constant features. Although genetically homogeneous, CACP exhibits significant intra- and interfamilial phenotypic variability due to secondary genetic factors, environmental modifiers, and complex molecular mechanisms. Camptodactyly is symmetrical, with variable distribution. It may affect fingers or toes and can be congenital or develop during childhood. Arthropathy is symmetrical, primarily involving large joints (wrists, knees, ankles, elbows, and hips). Coxa vara is present in 50-90% of cases, is progressive, and tends to worsen with age. Spinal abnormalities such as lordosis, scoliosis, and kyphosis are possible, though the cervical spine is generally spared. The articular manifestations of CACP syndrome may mimic juvenile idiopathic arthritis (JIA), and patients are often initially misdiagnosed and treated inappropriately. Joints appear swollen due to non-inflammatory synovial effusion and synovial thickening. They develop contractures, functional limitations, and sometimes musculoskeletal pain. Non-inflammatory pericarditis is reported in 30% of published cases, with variable clinical courses that may require surgical intervention in cases of constrictive pericarditis. The routine pathway of assessments and follow-up for patients with CACP syndrome includes an initial detailed evaluation and regular monitoring. Following the diagnosis, which is based on clinical history, imaging studies, and genetic confirmation of PRG4 mutations, patients undergo periodic clinical visits, generally scheduled every six months. During these visits, the progression of the disease, articular symptoms (e.g., camptodactyly, mobility limitations), and possible extraarticular complications, such as pericarditis, are assessed. Radiological (e.g., X-rays, MRI) and laboratory assessments, however, can be spaced out over longer intervals compared to the schedule of clinical visits, typically every 1-2 years, unless specific indications arise. Nonetheless, these examinations may be requested based on contingent clinical needs, such as a sudden worsening of symptoms or suspicion of complications. This flexible approach helps to balance thorough disease monitoring with minimizing the burden on patients, while ensuring personalized and timely management of the condition. At present, there is no specific pharmacological treatment for CACP. Management is primarily symptomatic and aimed at preventing joint deformities and extra-articular complications. Currently, no experimental therapies are available for CACP syndrome, but future research could explore gene therapy, regenerative medicine, and biologics. This study, involving pediatric and pediatric rheumatology centers across Italy and Europe, aims to collect epidemiological, clinical, and therapeutic data from a large cohort of patients. Its goals include better defining the disease's characteristics, understanding its natural history, and evaluating different therapeutic approaches and their efficacy. The study will also analyze potential genotypephenotype correlations.

Transition to KPL-387 Monotherapy Dosing & Administration Study

The primary objective of this study is to characterize the efficacy and safety of dosing regimens used to transition from prior pericarditis therapies to KPL-387 monotherapy in participants with well-controlled recurrent pericarditis on standard therapies.

COVID-19 Vaccine-induced Inflammatory Heart Disease Prevalence Registry

Myocarditis and pericarditis are inflammatory diseases of the myocardium and pericardium, and can be related to different causes, including vaccines. In the past, some people developed inflammatory heart disease after receiving a live or inactive virus vaccine (smallpox vaccine or flu vaccine). Myocarditis was also seen in people with COVID-19. More recently, many countries reported that some people have developed an inflammatory condition of the myocardium or pericardium after receiving a vaccine for COVID-19. After the COVID-19 vaccination campaigns, doctors have noticed more people presenting to the Emergency Department with chest pain and shortness of breath after receiving the vaccine, symptoms that resemble myocarditis or pericarditis. These symptoms may start between 2 to 10 days following vaccination and are frequently noticed after the second dose of the vaccines. While pericarditis seems to affect people of various age groups and gender, myocarditis is more commonly seen in young males. The study will consist of two components. 1) The vaccine-induced inflammatory heart disease database will be established. There will be a retrospective chart review looking at vaccine myocarditis/pericarditis (Brighton Criteria Levels 1-3). 2\) There will be a prospective, pragmatic design case-control study for vaccine myocarditis/pericarditis. Follow-up telephone interview will be conducted at 6 months, 12 months and yearly up to 4 years. A record search will also be performed at 6 months, 12 months and yearly for 4 years. The retrospective component of the study will be conducted by identifying patients previously diagnosed with this condition at participating centres.

Pericardial Imaging Study

The pericardium is a thin, double-layered sac around the heart that helps reduce friction as the heart moves. When this sac gets inflamed, it is called pericarditis, which can cause serious health problems and even be life-threatening. Pericarditis often comes back after the first episode. About 10-30% of people will have it again, and half of those will have it multiple times. Although there are treatments available, they are costly and not often used because we can't predict who best to use them on. Finding a way to predict which patients would benefit from these treatments could help reduce the burden on patients and the healthcare system. This study will use a test called an 18F-FDG PET/CT with CTA Scan (18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computer tomography angiography (CTA)) to measure inflammation in the pericardium. The purpose of the study is to create easy-to-use tools for doctors to identify people at high risk of pericarditis coming back, so they can get advanced treatment early. This study will help fill knowledge gaps about key predictors like clinical signs, blood tests, and imaging results.

RUDRA Registry (Real-World Clinical Registry for Patients With Recurrent Pericarditis)

А multicenter, non-interventional real world clinical registry of patients with recurrent pericarditis. The main goal of the registry is to epidemiologically assess the pattern, clinical outcomes, and approaches to therapy in patients with recurrent pericarditis.

EACVI Study on Multimodality Cardiovascular Imaging of Inflammatory Cardiovascular Diseases

Inflammatory Cardiovascular Diseases and Autoimmune Rheumatic Diseases (ICARDs) encompass cardiovascular involvement in connective tissue diseases, vasculitis, and primary inflammatory cardiac processes affecting all layers of the heart. ICARDs are associated with increased cardiovascular morbidity and mortality, independently of traditional risk factors, via multiple pathophysiological mechanisms. Diagnosis and prognosis are challenged by the heterogeneity of clinical presentations. Multimodality cardiovascular imaging - including cardiovascular magnetic resonance (CMR), transthoracic echocardiography, and positron emission tomography (PET) - plays a central role in detecting and characterizing inflammatory involvement, and may offer prognostic insights. Given the limited data on the diagnostic and prognostic utility of these imaging modalities in ICARDs, the EACVI-INFLAME study aims to assess the prevalence of confirmed cardiovascular involvement in patients with suspected or established ICARDs undergoing CMR and/or cardiac PET in a multicentric international cohort.

COR-INSIGHT: Optimizing Cardiovascular and Cardiopulmonary Outcomes with AI-Driven Multiplexed Indications Using COR ECG Wearable

The COR-INSIGHT trial aims to evaluate the effectiveness of Peerbridge COR advanced ambulatory ECG wearables (COR 1.0 and COR 2.0) in accurately and non-invasively detecting cardiovascular and cardiopulmonary conditions using AI-based software (CardioMIND and CardioQSync). The study devices offer non-invasive, multiplexed, AI-enabled direct-from-ECG detection as a novel alternative to traditional diagnostic methods, including imaging, hemodynamic monitoring systems, catheter-based devices, and biochemical assays. Continuous COR ECG data collected in hospital, outpatient clinic, or home settings will be analyzed to evaluate the predictive accuracy, sensitivity, specificity, and performance of these devices in differentiating between screen-positive and screen-negative subjects. The panel of screened indications encompasses a broad spectrum of clinically relevant cardiovascular, cardiopulmonary, and sleep-related diagnostic parameters, which are critical for advanced patient assessment and management. In the cardiovascular domain, the protocol emphasizes the detection and classification of heart failure, assessment of ejection fraction severity, and identification of myocardial infarction, including pathological Q-waves and STEMI. It further addresses diagnostic markers for arrhythmogenic conditions such as QT interval prolongation, T-wave alternans, and ventricular tachycardia, as well as insights into ischemia, atrial enlargement, ventricular activation time, and heart rate turbulence. Additional parameters, such as heart rate variability, pacing efficacy, electrolyte imbalances, and structural abnormalities, including left ventricular hypertrophy, contribute to comprehensive cardiovascular risk stratification. In the non-invasive cardiopulmonary context, the protocol incorporates metrics like respiratory sinus arrhythmia, cardiac output, stroke volume, and stroke volume variability, providing critical insights into hemodynamic and autonomic function. The inclusion of direct-from-ECG metrics for sleep-related disorders, such as the apnea-hypopnea index, respiratory disturbance index, and oxygen saturation variability, underscores the protocol's utility in addressing the intersection of cardiopulmonary and sleep medicine. This multifaceted approach establishes a robust framework for precision diagnostics and holistic patient management. The COR 1.0 and COR 2.0 wearables provide multi-lead ECG recordings, with COR 2.0 offering extended capabilities for cardiopulmonary metrics and longer battery life (up to 14 days). COR 2.0 supports tri-modal operations: (i) Extended Holter Mode: Outputs Leads II and III, mirroring the functionality of COR 1.0 for broader ECG monitoring applications. (ii) Cardiopulmonary Mode: Adds real-time recording of Lead I, V2, respiratory impedance, and triaxial accelerometer outputs, providing advanced cardiopulmonary insights. (iii) Real-Time Streaming Mode: Streams data directly to mobile devices or computers via Bluetooth Low Energy (BLE), enabling real-time waveform rendering and analysis. The COR 2.0 units are experimental and not yet FDA-cleared. Primary endpoints include sensitivity (true positive rate) \> 80%, specificity (true negative rate) \> 90%, and statistical agreement with reference devices for cardiovascular, cardiopulmonary, and sleep metrics. Secondary endpoints focus on predictive values (PPV and NPV) and overall diagnostic performance. The study employs eight distinct sub-protocols (A through H) to address a variety of cardiovascular, cardiopulmonary, and sleep-related diagnostic goals. These sub-protocols are tailored to specific clinical endpoints, varying in duration (30 minutes to 14 days) and type of data collection. Up to 15,000 participants will be enrolled across multiple sub-protocols. Screening ensures eligibility, and subjects must provide informed consent before participation. Dropouts and non-compliant subjects will be excluded from final analyses.

Inflammatory Cardiomyopathy Bern Registry

Inflammatory cardiomyopathies are associated with inflammation and impaired function of the heart muscle and encompass myo- and pericarditis and cardiac sarcoidosis. Due to the heterogeneity of the clinical manifestations, establishing the diagnosis and prediction of outcome is challenging. Specifically for myocarditis, it is associated with acute and chronic heart failure and sudden cardiac death. Cardiac magnetic resonance imaging (CMR) allows imaging of tissue characteristics (i.e. edema and fibrosis). CMR is the primary diagnostic tool in myocarditis and can also be used for differentiating other inflammatory diseases. Beside the presence of edema, also hyperemia/capillary leak, fibrosis and myocardial function can be assessed and quantified. Previous studies demonstrated the prognostic role of CMR features beyond traditional markers of LV function, but are limited to smaller cohorts and single-center studies. Furthermore, CMR is a rapidly developing modality and as new features of the modality become available, additional research is needed to identify which combination of parameters optimize risk stratification of this heterogenous inflammatory cardiomyopathy. Hence, the goal of the registry is to investigate the diagnostic and prognostic role of clinical techniques in inflammatory cardiomyopathies, particularly CMR, and which combination of features provide the highest potential. This analysis will include new advanced CMR techniques but will also assess the role of other techniques that may be more cost-efficient and more widely available, which could be used as a precursor to CMR imaging exams.

Clinical Phenotypes in Pericarditis: IL-1RA Antibodies and suPAR Levels

This study aims to investigate the pathophysiology of recurrent pericarditis (RP) by testing for neutralizing autoantibodies against interleukin-1 receptor antagonist (IL-1RA) and measuring soluble urokinase plasminogen activator receptor (suPAR) levels. The hypothesis is that these tests will provide insights into both the inflammatory and non-inflammatory phenotypes of RP, shedding light on the underlying mechanisms. The study will assess the correlation between antibody levels, suPAR levels, and markers of cardiac damage and inflammation. Longitudinal testing during acute episodes and intercritical phases is also planned. The results may guide the use of anakinra, an IL-1 receptor antagonist, in specific clinical scenarios and optimize treatment strategies for RP.

Inflammation in Acute Cardiovascular Diseases - the CArdiovascular Inflammation Registry (CAIR)

Following acute cardiovascular injury, inflammation is vital to activate reparative mechanisms. However, there is compelling evidence implicating excessive inflammation and dysregulated resolution in fibrosis, ventricular remodelling, and heart failure (HF). Recently, the anti-inflammatory agent colchicine reduced cardiovascular events after myocardial infarction (MI) compared to placebo, indicating that targeting inflammation in acute cardiovascular conditions is feasible. Several acute cardiovascular conditions are characterised by inflammation, including myocarditis, MI, and acute heart failure. However, there is large variability in definition, epidemiology, clinical presentation, pathophysiology, and natural history of acute inflammatory cardiovascular diseases. This relates, in part, to the difficulty in performing adequately powered studies. Clinical studies that include sufficient patients and extended observation periods are necessary to address some of these knowledge gaps. This registry aims to collate routinely collected clinical data on patients with acute cardiovascular diseases characterised by inflammation in an observational-based registry. By doing so, the investigators hope to understand the contribution of inflammation to the pathophysiology of acute cardiovascular disease, improve risk stratification, and identify potential novel therapeutic targets.

Therapeutic Approach in Colchicine-resistant Recurrent pEricarditis in Children

The purpose of this study is to demonstrate that anakinra provides more rapid disease control than steroids in the first month of treatment in the event of recurrent pericarditis and is more effective in preventing further exacerbations in patients aged between eight months and eighteen years of age with idiopathic or post-procedural pericarditis, unresponsive to first-line treatment with NSAIDs and colchicine at the appropriate dosage, or in case of colchicine intolerance. The efficacy of the two treatments will be evaluated by the capacity and timing of the two therapies to determine a complete control (clinical, laboratory and instrumental) of the disease and the absence of recurrences.