Harlan, Kentucky
A Study to Evaluate the Efficacy and Safety of Once-Weekly MET097 in Adults With Obesity or Overweight and T2DM
This is a 28-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study to investigate the efficacy, safety, and tolerability of four different once-weekly MET097 dosing regimens vs. placebo for body weight loss in adults (18-75 years of age) with obesity or overweight (body mass index [BMI] ≥27 to ≤50 kg/m2) and T2DM . After completing 28 weeks of study treatment, all participants will be followed for approximately 4 weeks after administration of the last dose of study treatment.
Phase
2Span
68 weeksSponsor
MetseraCincinnati, Ohio
Recruiting
Non-Invasive Quantification of Liver Health in NASH (N-QUAN)
NASH trials will often use the criteria proposed by the NASH Clinical Research Network (NASH-CRN), the NAS scoring system, to classify patients as suitable for study enrolment. NAS is a summation of the histology scores for fat (0-3), inflammation (0-3), and ballooning (0-2) with a score of 4 or 5 or higher regarded as NASH. Whilst the score doesn't include fibrosis, the rapidly evolving clinical trials landscape in NASH has seen a shift in emphasis from drugs proposed to target liver fat to the targeting of fibrosis. This was due to observations contrary to the previously held belief that fibrosis could not improve, and the data to support fibrosis being predictive of clinical outcomes. As a result, many clinical trials now require patients to have a NAS ≥4 or 5, with the regulatory accepted criteria requirement for at least a score of 1 for inflammation and 1 for ballooning, and evidence of fibrosis of stage 2 or more (scored using the Kleiner-Brunt (0-4) scale). The route by which a liver biopsy is indicated for inclusion to a clinical trial is usually based on patient presentation and clinical work-up. In the Primary care patient presents with clinical risk factors for NASH like metabolic syndrome. Blood biomarkers will be checked and if raised patient will be referred to the hepatology. In the secondary care patient might have a transient elastography and if CAP is equal or more than 280 and LSM is equal or more than 7 kPa, patient will have biopsy. However clinical risk factors are often not sensitive enough, and NASH trials often suffer from high levels of screen fails at biopsy, meaning a large proportion are unnecessarily biopsied. Screening strategies are becoming increasingly more popular in order to reduce the number that fail screening and metrics derived from magnetic resonance imaging (MRI) such as T1-mapping and PDFF are emerging as promising diagnostic screening biomarkers in NASH. MRI exploits the magnetic properties of hydrogen nuclei protons within a determined magnetic field. T1 mapping measures longitudinal relaxation time, a measure of how long it takes for protons to re-equilibrate their spins to the magnetic field after being excited by a radiofrequency pulse, and thus is an indicator of regional tissue water (proton) content. T1 mapping has shown promise as an effective biomarker of liver inflammation and fibrosis, as T1 relaxation time lengthens with increases in extracellular fluid (which may be caused by fibrosis and/or inflammation). The presence of iron however, which can be accurately measured from MRI-T2star (T2*) relaxation time, shortens the T1, and thus must be accounted for. An algorithm has been created (Perspectum Diagnostics) that allows for the bias introduced by elevated iron to be removed from the T1 measurements, yielding the iron corrected T1 (cT1). Iron corrected T1 (cT1) has been shown to correlate with fibro-inflammatory disease and can effectively stratify patients with NASH and cirrhosis (7). MRI-PDFF is a ratio, expressed as a percentage, of the fraction of the MRI-visible protons attributable to fat divided by all MRI-visible protons in that region of the liver attributable to fat and water. Taking advantage of the chemical shift between fat and water, pulse sequences including fast spin echo and gradient-recalled echo (GRE) sequences can be used to acquire images at multiple echo times at which fat and water signals have different phases relative to each other. PDFF has been shown to have excellent correlation between histologically graded steatosis across the clinical range seen in NASH and high diagnostic accuracy in stratification of all grades of liver steatosis, although it is weaker in the presence of advanced fibrosis. Whilst PDFF does not correlate with other features of NASH, it has been reported that NAFLD patients with grade one steatosis are more likely to have characteristics of advanced liver disease such as fibrosis and ballooning, and changes in hepatic steatosis may be correlated with changes in other histological endpoints. Thus whilst some authors advise caution about using PDFF as a biomarker of NASH it has been well accepted by the NASH community as a biomarker for both enrolment and as an endpoint in NASH clinical trials (e.g. MOZART: NCT01766713; FLINT: NCT01265498). Where cT1 appears to have an advantage over PDFF as a non-invasive biomarker for NASH, is in detection of patients with both disease activity (ballooning and inflammation) and fibrosis as cT1 has been reported to be correlated with ballooning, fibrosis and NAFLD activity score, and has been shown to predict clinical outcomes. As such it is emerging as a promising biomarker for both screening and as an endpoint in NASH clinical trials (NCT02421094; NCT02912260) particularly those investigating mechanisms of action of fibro-inflammation, or for distinguishing those with more advanced NASH with fibrosis. Both cT1 and PDFF can be acquired as part of the LiverMultiScan™ (LMS) imaging protocol (Perspectum Diagnostics Ltd, UK). Based on the data reported in the literature, and from our preliminary analysis of N=109 biopsy-confirmed NAFL patients recruited from the two UK studies, both cT1 and PDFF appear to have potential to become diagnostic biomarkers, that may have utility for clinical trial population enrichment when used in conjunction with clinical risk factors. Specifically, for PDFF to identify participants who are more likely to have histopathologic findings of steatosis, and cT1 to identify participants who are more likely to have histopathologic findings of NASH, and NASH with fibrosis. The primary objective of this study is to evaluate cT1 (Corrected T1) as a diagnostic biomarker that can be used, in conjunction with clinical risk factors, to identify patients who are more likely to have liver histopathologic findings of non-alcoholic steatohepatitis (NASH). Ideally, this biomarker should identify patients with a non-alcoholic fatty liver disease activity score (NAS) ≥ 4 and liver fibrosis (NASH/CRN Brunt/Kleiner scale) ≥ stage 2 on histopathologic assessment. Based on our observations from earlier trials, our hypothesis is that we expect cT1 to have good diagnostic accuracy for discriminating those with NAS≥4 & F≥2 from those without
Phase
N/ASpan
195 weeksSponsor
PerspectumDallas, Texas
Recruiting
A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)
Phase
3Span
251 weeksSponsor
Madrigal Pharmaceuticals, Inc.Dallas, Texas
Recruiting
A Phase 3 Study Evaluating Efficacy and Safety of Lanifibranor Followed by an Active Treatment Extension in Adult Patients With (NASH) and Fibrosis Stages F2 and F3 ( NATiV3 )
Primary objectives This Phase 3 study is conducted to evaluate lanifibranor in adults with NASH and liver fibrosis stage F2 or F3 and consists of 2 sequential parts - an initial double-blind placebo-controlled (DBPC) period (Part A) followed by a double-blind active treatment extension (ATE) period (Part B), with the following primary objectives: Part A To assess the safety and efficacy of lanifibranor compared to placebo on 'NASH resolution and improvement of fibrosis' assessed by liver histology. Part B To assess the safety of lanifibranor beyond the DBPC period. Secondary objectives Key secondary objectives of Part 1: - To assess the effect of lanifibranor compared to placebo on NASH resolution and no worsening of fibrosis - To assess the effect of lanifibranor compared to placebo on improvement of fibrosis with no worsening of NASH Other secondary objectives of both Part 1 and Part 2: - To assess the effect of lanifibranor on other key histological features of NASH (only for DBPC period) - To assess the effect of lanifibranor on NASH resolution and improvement of fibrosis in diabetic patients (only for DBPC period) - To assess the effect of lanifibranor on liver tests - To assess the effect of lanifibranor on glycaemic parameters - To assess the effect of lanifibranor on lipid parameters - To assess the effect of lanifibranor on liver stiffness and steatosis assessed by elastography. - To assess the effect of lanifibranor on health-related quality of life - To assess the safety of lanifibranor - To assess population PK modeling through plasma levels of lanifibranor using sparse sampling scheme (only for DBPC period)
Phase
3Span
267 weeksSponsor
Inventiva PharmaDallas, Texas
Recruiting
Collection of Blood From Healthy Patients, Patients With Benign Disease and Patients With Cancer
Whole blood, plasma, and/or serum specimens will be collected from patients with active cancer, patients in cancer remission, patients diagnosed with benign disease, and healthy volunteers. These blood samples will be used to perform various studies to determine the utility of select DNA methylation markers for cancer diagnostic or prognostic indications.
Phase
N/ASpan
346 weeksSponsor
Helio GenomicsDallas, Texas
Recruiting
MILD® Percutaneous Image-Guided Lumbar Decompression: A Medicare Claims Study
In this study the treatment group will include all patients receiving MILD, and the control group will include all patients receiving IPD for the treatment of LSS during the enrollment period. Reoperation and harms data will be studied for the MILD and IPD procedures for a 24-month follow-up period after the index procedure using Medicare claims data. This study is exempt from IRB oversight (Department of Health and Human Services regulations 45 CFR 46) and does not require prior enrollment nor patient consent. The inclusion of the study's NCT number on MILD Medicare claims is required and results in enrollment.
Phase
N/ASpan
512 weeksSponsor
Vertos Medical, Inc.Dallas, Texas
Recruiting
A Study to Explore the Incidence of Influenza and Respiratory Syncytial Virus (RSV) in Adults Hospitalized With Acute Respiratory Tract Infection
Phase
N/ASpan
159 weeksSponsor
Janssen Research & Development, LLCDallas, Texas
Recruiting
Dallas, Texas
Recruiting
Healthy Volunteers
A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
Phase
3Span
470 weeksSponsor
Akero Therapeutics, IncDallas, Texas
Recruiting
Dallas, Texas
Recruiting