A5105827752- Muscle Physiology and Disorders
- Rheumatoid Arthritis Research and Therapies
- Systemic Lupus Erythematosus Research
- SARS-CoV-2 and COVID-19 Research
- Computational Drug Discovery Methods
- Cytokine Signaling Pathways and Interactions
- Muscle activation and electromyography studies
- Neuropeptides and Animal Physiology
- Systemic Sclerosis and Related Diseases
- Exercise and Physiological Responses
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- COVID-19 Clinical Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Cardiomyopathy and Myosin Studies
- Lymphoma Diagnosis and Treatment
- HER2/EGFR in Cancer Research
- Dermatology and Skin Diseases
- Protease and Inhibitor Mechanisms
- Psoriasis: Treatment and Pathogenesis
- Prosthetics and Rehabilitation Robotics
- Synthesis of Tetrazole Derivatives
- Cancer therapeutics and mechanisms
- Dermatologic Treatments and Research
- Research on Leishmaniasis Studies
Pfizer (United States)
2015-2023
Pfizer (United Kingdom)
2023
GlaxoSmithKline (United Kingdom)
2006-2016
GlaxoSmithKline (Netherlands)
2015
Age UK
2007-2012
The Royal Free Hospital
2001
University College London
2001
Coronavirus disease 2019 (COVID-19) is a continued leading cause of hospitalization and death. Safe, efficacious COVID-19 antivirals are needed urgently. Nirmatrelvir (PF-07321332), the first orally bioavailable, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) Mpro inhibitor against coronaviridae family, has demonstrated potent preclinical antiviral activity benign safety profile. We report safety, tolerability, pharmacokinetic data nirmatrelvir with without ritonavir as...
<h3>BACKGROUND</h3> Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment been shown to influence the outcome significantly affect score, though many of immunosuppression have tried. Recent developments haemopoietic stem cell transplantation (HSCT) allowed application profound followed by HSCT, rescue, autoimmune diseases such as SSc. <h3>METHODS</h3> Results for 41 patients included continuing...
Nirmatrelvir coadministered with ritonavir is highly efficacious in reducing the risk of coronavirus disease 2019 (COVID‐19) adverse outcomes among patients at increased progression to severe disease, including chronic kidney disease. Because nirmatrelvir eliminated by kidneys when given ritonavir, this phase I study evaluated effects renal impairment on pharmacokinetics, safety, and tolerability nirmatrelvir/ritonavir. Participants normal function ( n = 10) or mild, moderate, 8 each) were...
Abstract Objective To determine whether the plasma levels of a range inflammatory proteins have utility as biomarkers disease activity in rheumatoid arthritis (RA) patients. Methods Plasma (n = 163) were profiled 44 patients with RA diagnosed according to American College Rheumatology 1987 criteria (22 active and 22 quiescent disease) 16 age‐ sex‐matched healthy controls. The subset differentially expressed predictors was investigated using partial least‐squares discriminant analysis, their...
GSK2586184 is a selective oral Janus kinase (JAK)1 inhibitor being evaluated as treatment for moderate-to-severe plaque-type psoriasis.To assess the relationship between dose of and clinical response, primarily by Psoriasis Area Severity Index (PASI).Sixty patients with plaque psoriasis were randomized to cohort A: 100 mg, 200 mg or 400 twice daily placebo; eight open-label B, small exploratory treated daily, explore differential gene expression.At week 12, 75% reduction in PASI (PASI 75)...
High variability in patients' changes 6 minute walk distance (6MWD) over time has complicated clinical trials of treatment efficacy Duchenne muscular dystrophy (DMD). We assessed whether boys with DMD could be grouped into classes that shared similar ambulatory function trajectories as measured by 6MWD. Ambulatory aged 5 years or older genetically confirmed who were enrolled a natural history study at 11 care centers throughout Italy included. For each boy, standardized assessments 6MWD...
We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) DMD, 80 were treated multiple ascending doses (5, 20, 40 mg/kg) placebo. The primary endpoints safety mean change 4-stair climb (4SC) time at week 49. Secondary included other functional tests, pharmacokinetics, pharmacodynamics. Mean (SD) age was 8.4 (1.7) 9.3...
Abstract Several recent publications have established a strong association between anti-cyclic citrullinated peptide antibody (anti-CCP)-positive rheumatoid arthritis (RA) and carriage of shared epitope (SE) alleles. Although anti-CCP also been associated with more severe RA, the issue whether this is independent factor (RF) has not addressed. To identify associations RF, anti-CCP, SE status radiological damage, we studied large cross-sectional cohort longstanding RA. Individuals ( n = 872)...
Abstract Objective Recent evidence has highlighted a major genetic contribution to radiographic damage in rheumatoid arthritis (RA). The objective of this study was determine whether variants the loci for interleukin‐1 (IL‐1), IL‐6, IL‐10, protein tyrosine phosphatase N22 (PTPN22), and selenoprotein S are associated with damage. Methods Modified Larsen scores were determined cross‐sectional population patients RA (n = 964). Rheumatoid factor (RF) anti–cyclic citrullinated peptide (anti‐CCP)...
Abstract Objective The HLA–DRB1 locus within the major histocompatibility complex (MHC) at 6p21.3 has been identified as a susceptibility gene for rheumatoid arthritis (RA); however, there is increasing evidence of additional genes in MHC region. aim this study was to estimate their number and location. Methods A case–control performed involving 977 control subjects 855 RA patients. genotyped together with 2,360 single‐nucleotide polymorphisms Logistic regression used detect DRB1‐independent...
We aimed to evaluate the pharmacodynamics, efficacy, safety and tolerability of JAK1 inhibitor GSK2586184 in adults with systemic lupus erythematosus (SLE). In this adaptive, randomized, double-blind, placebo-controlled study, patients received oral 50-400 mg, or placebo twice daily for 12 weeks. Primary endpoints included interferon-mediated messenger RNA transcription over time, changes Safety Estrogen Lupus National Assessment-SLE Disease Activity Index score, number/severity adverse...
Representatives of academia, patient organisations, industry and the United States Food Drug Administration attended a workshop on dystrophin quantification methodology. The aims were to provide an overview methods used quantify levels in human skeletal muscle their applicability clinical trial samples, outline gaps with regards validating for robust applications prior regulatory agency review, align future efforts towards further optimizing these methods. facilitated constructive but also...
Abstract Safety, tolerability, anabolic effects, pharmacokinetics, and pharmacodynamics of single ascending multiple doses domagrozumab, an antimyostatin monoclonal antibody, were assessed following intravenous (IV) subcutaneous (SC) administration in healthy subjects. A range dose levels between 1 40 mg/kg IV (3 doses) 10 tested (n = 8 per cohort). Additionally, a 3 SC 8) cohort also received domagrozumab. Magnetic resonance imaging whole‐body dual‐energy x‐ray absorptiometry conducted to...
Aim: Using baseline data from a clinical trial of domagrozumab in Duchenne muscular dystrophy, we evaluated the correlation between functional measures and quantitative MRI assessments thigh muscle. Patients & methods: Analysis included timed tests, knee extension/strength North Star Ambulatory Assessment. (n = 120) underwent examinations one thigh, with sequences to enable measurements muscle volume (MV), MV index, mean T2 relaxation time via T2-mapping fat fraction. Results: was moderately...
Objective. To investigate the stability over 2 weeks of ultrasonographic assessments synovial thickness and vascularity in all 10 metacarpophalangeal joints subjects with rheumatoid arthritis (RA) a range disease activities as measured by validated Disease Activity Score-28 joint score (DAS28-ESR). And severe activity, to compare sensitivity these measurements, acute-phase markers, vascular endothelial growth factor change response oral prednisolone (7.5 mg daily). Methods. A group 38 RA...
Abstract Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disorder caused by mutations in the DMD gene, leading to severe reduction or absence of protein dystrophin. Gene therapy strategies that aim increase expression functional dystrophin (mini-dystrophin) are under investigation. The ability accurately quantify dystrophin/mini-dystrophin essential assessing level gene transduction. We demonstrated validation and application novel peptide immunoaffinity liquid...
Abstract Background An urgent need remains for antiviral therapies to treat patients hospitalized with COVID-19. PF-07304814—the prodrug (lufotrelvir) and its active moiety (PF-00835231)—is a potent inhibitor of the SARS-CoV-2 3CL protease. Method Eligible participants were 18 79 years old confirmed This first-in-human phase 1b study was designed 2 groups: single ascending dose (SAD) multiple (MAD). Participants could receive local standard-of-care therapy. In SAD, randomized 24-hour...
Abstract The enzyme methionine aminopeptidase-2 (MetAP-2) is thought to play an important function in human endothelial cell proliferation, and as such provides a valuable target both inflammation cancer. Rheumatoid arthritis (RA) chronic inflammatory disease associated with increased synovial vascularity, hence potential therapeutic for angiogenesis inhibitors. We examined the use of PPI-2458, selective non-reversible inhibitor MetAP-2, models RA, namely acute collagen-induced (CIA) mice....
<h3>Objective:</h3> To investigate the association of a recently described classification Human leukocyte antigen (HLA)-DRB1 shared epitope alleles with rheumatoid factors (RF) and anti-cyclic citrullinated peptide (CCP) production radiological severity in arthritis (RA). <h3>Methods:</h3> Patients RA (n = 962) were studied. Genotyping DRB1 assays for RF anti-CCP performed. Radiological was measured using modified Larsen score. <h3>Results:</h3> In accordance previous reports, we found...
Abstract An important feature of autoimmune diseases is the overlap pathophysiological characteristics. Clustering in families suggests that genetic variants may contribute to autoimmunity. The aim present study was investigate role interferon induced with helicase domain 1 (IFIH1) A946T (rs1990760 A>G) variant rheumatoid arthritis (RA), as this recently associated susceptibility type diabetes. A total 965 Caucasians RA and 988 healthy controls were genotyped for IFIH1 A946T. Gene...
Abstract Studies on targeted antivirals for treatment of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the cause ongoing pandemic, are limited. PF‐07304814 (lufotrelvir) is phosphate prodrug PF‐00835231, a protease inhibitor targeting 3C‐like SARS‐CoV‐2. This phase 1 study evaluated safety, tolerability, and pharmacokinetics (PK) single ascending intravenous doses lufotrelvir (continuous 24‐hour infusion 50, 150, 500, or 700 mg) versus placebo in healthy volunteers (2...
Aim: Evaluate the utility of glutamate dehydrogenase (GLDH) and cardiac troponin I as safety biomarkers, creatine kinase muscle injury panel health biomarkers in Duchenne muscular dystrophy. Patients & methods: Data were collected during a Phase II trial domagrozumab. Results: GLDH was more specific biomarker for liver than alanine aminotransferase. Cardiac elevations variable not sustained, limiting its applicability biomarker. Muscle no informative Conclusion: Results support use patients...