A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects With Light Chain (AL) Amyloidosis

A Phase 3 study to evaluate the efficacy and safety of birtamimab plus standard of care compared to placebo plus standard of care in Mayo Stage IV patients with AL amyloidosis.

开始日期2021-08-30

申办/合作机构

Prothena Biosciences Ltd.

EUCTR2021-000037-14-ES / Unknown status临床3期

开始日期2021-07-01

申办/合作机构

Prothena Biosciences Ltd.

NCT03879278 / Terminated临床1期

A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of NPT189 in Healthy Subjects

This will be a Phase 1, randomized, double-blind, single center, placebo-controlled, multiple ascending dose (MAD) study in a maximum of 3 cohorts of 8 healthy male and female subjects each. Subjects in Cohorts 1, 2 and 3 will receive ascending multiple IV doses of NPT189 or matching placebo.

开始日期2019-03-06

申办/合作机构

Proclara Biosciences, Inc.

100 项与淀粉样蛋白轻链相关的临床结果

登录后查看更多信息

100 项与淀粉样蛋白轻链相关的转化医学

登录后查看更多信息

0 项与淀粉样蛋白轻链相关的专利（医药）

登录后查看更多信息

221

项与淀粉样蛋白轻链相关的文献（医药）

2024-04-01·Human Pathology

Morphological findings in different subtypes of hepatic amyloid

Article

作者: Yasir, Saba ; Zhang, Lizhi ; Torbenson, Michael ; Chen, Zongming Eric ; Hartley, Chris

The classic findings have been well described for light-chain amyloid involving the liver. In addition to light chain, however, many additional proteins are now known to be amyloidogenic and can involve the liver. A total of 58 surgical pathology specimens with amyloid deposits were analyzed for patterns of amyloid deposition, including amyloid from light chain lambda (N = 17), light chain kappa (N = 15), transthyretin (N = 15), serum amyloid A (N = 4), apolipoprotein A1 (N = 4), fibrinogen alpha (N = 2), LECT2 (N = 1). Amyloid deposits predominately targeted the liver vasculature, including the walls of the hepatic arteries, portal veins, and sinusoids. While there was overlap, light chain amyloid predominately involved the sinusoids, while transthyretin amyloid predominately targeted the hepatic arteries, especially the larger ones in the hilum and larger portal tracts. Serum amyloid A formed nodular deposits that started in the portal vasculature but then extended into the portal tract stroma, leading to large, bulbous, portal-based amyloid deposits. Apolipoprotein A amyloid also formed large portal-based nodules. Fibrinogen was mild and subtle on H&E and predominately affected portal veins. Amyloid deposits in hilar nerves were prominent with amyloid light chain, transthyretin, and apolipoprotein A1. In conclusion, the histology of hepatic amyloid is diverse and shows several distinct clusters of findings that can aide in recognition in surgical pathology specimens.

2023-12-01·Fish and shellfish immunology reports

Expression of genes encoding non-specific immunity, anti-oxidative status and aquaporins in β-glucan-fed golden mahseer (Tor putitora) juveniles under ammonia stress.

Article

作者: Tripathi, Priyanka H ; Ciji, Alexander ; Akhtar, Md Shahbaz ; Pandey, Anupam

The study investigated the effects of dietary administration of β-glucan on aquaporins and antioxidative & immune gene expression in endangered golden mahseer, Tor putitora juveniles, exposed to ammonia stress. For that, fish were fed experimental diets having 0 (control/basal), 0.25, 0.5, and 0.75% β-d-glucan for five weeks and then exposed to ammonia (10 mgL^-1 total ammonia nitrogen) for 96 h. Administration of β-glucan differentially influenced the mRNA expression of aquaporins, anti-oxidative, and immune genes in ammonia-exposed fish. For instance, the transcript abundance of catalase and glutathione-s-transferase in gill varied significantly among the treatment groups, with the lowest levels in 0.75% β-glucan fed groups. At the same time, their hepatic mRNA expression was similar. Congruently, transcript abundance of inducible nitric oxide synthase considerably decreased in the β-glucan fed ammonia-challenged fish. Conversely, the relative mRNA expression of various immune genes viz., major histocompatibility complex, immunoglobulin light chain, interleukin 1-beta, toll-like receptors (tlr4 and tlr5) and complement component 3 remained largely unchanged in ammonia-exposed mahseer juveniles that were fed with graded levels of β-glucan. On the other hand, a significantly lower transcript level of aquaporins 1a and 3a was noticed in the gill of glucan-fed fish compared to ammonia-exposed fish that received the basal diet. However, branchial aquaporin 3b remained unaltered. Altogether, this study showed that dietary intake of 0.75% β-glucan improved resistance to ammonia stress to a certain degree, probably through activating anti-oxidative system and reducing brachial ammonia uptake.

2023-12-01·BMJ Case Reports

Acute myositis secondary to Epstein-Barr virus in the absence of infectious mononucleosis with severe rhabdomyolysis

Article

作者: Lent, Dale ; Goldman, John ; Tuchinsky, Adam ; Montalvo, Angela

SummaryRhabdomyolysis is characterised by muscle breakdown which causes myoglobin light chain release and can result in renal injury. While some of the most common causes of rhabdomyolysis are trauma related, others include toxins, autoimmune processes or viral aetiologies. We present the case of a 20s-year-old man, with no significant medical history, who presented to the emergency department with a 1-week history of weakness, myalgias, nausea, vomiting and subjective fevers. A review of systems and physical exam were otherwise unremarkable, including being negative for sore throat, dysphagia and lymphadenopathy. On presentation, the patient was noted to have dark urine with a creatine kinase value of 452 458 U/L and an elevated creatinine at 7.23 mg/dL. The patient denied any trauma or increased physical activity. His toxin screen and autoimmune workup were negative. The patient’s serological workup was significant for acute Epstein-Barr virus (EBV) infection, without additional viral coinfection or mononucleosis. During his hospitalisation course, the patient was managed with supportive care including haemodialysis. The patient made a full renal recovery and was discharged with scheduled outpatient follow-up. This case highlights the recognition of an acute EBV infection causing rhabdomyolysis in the absence of mononucleosis or concomitant infection.

项与淀粉样蛋白轻链相关的新闻（医药）

2023-12-19

·GlobeNewswire-Health Care

AC Immune’s Targeted Anti-pTau Active Immunotherapy for Alzheimer’s Disease Advances into Phase 2b Trial

AC Immune’s Targeted Anti-pTau Active Immunotherapy for Alzheimer’s Disease Advances into Phase 2b Trial Potentially registration-enabling Phase 2b study (ReTain) will evaluate the effect of ACI-35.030 on cognition and Tau pathology in approximately 500 participants with preclinical Alzheimer’s disease (AD) Anti-pTau active immunotherapy being designed to potentially prevent or reduce cognitive decline could address need of over 315 million people globally1 with preclinical AD AC Immune to receive approximately CHF 40 million in total milestone payments under terms of the licensing agreement, following trial initiation and enrollment milestone AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, today announced that its development partner has programmed the launch of a Phase 2b clinical study to evaluate ACI-35.030 (JNJ-64042056) in patients with preclinical Alzheimer’s disease (AD), those individuals not yet showing symptoms. ACI-35.030 is an investigational targeted active immunotherapy, selective for pathological phosphorylated Tau (pTau). Studies have shown that pTau correlates with AD progression and the trial aims to show that ACI-35.030 can prevent or slow down the progression of tau pathology and onset of clinical symptoms. Under the terms of the licensing agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company, AC Immune will now receive a milestone payment of CHF 15 million and will receive another milestone payment of CHF 25 million related to achieving a non-disclosed enrollment target. The partnership with Janssen aims to develop and commercialize therapeutic anti-Tau active immunotherapies for the treatment of AD and potentially other Tauopathies. Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: “In the recently completed Phase 1b/2a trial, data showed that ACI-35.030 was able to activate patients’ immune systems with a robust polyclonal antibody response against phosphorylated Tau and its neurotoxic aggregated form, which is believed to contribute to the pathology and progression of Alzheimer’s disease. Our partner’s decision to move forward with this robust clinical trial shows that treatment with this active immunotherapy so early in the disease process that individuals are not yet showing symptoms, holds tremendous promise to slow or possibly even prevent progression to symptomatic AD.” The Phase 2b ReTain trial is a potentially registration-enabling trial and is a randomized, multicenter, double-blind, placebo-controlled clinical study in participants with preclinical AD to assess the clinical effect of active immunization with ACI-35.030. It is designed to test the hypothesis that ACI-35.030 has a disease-modifying effect that can delay or prevent the onset of cognitive impairment or other clinical symptoms in individuals with preclinical AD through inhibition of seeding and spreading of pathological Tau. Approximately 500 participants with preclinical AD (cognitively normal, amyloid positive, Tau positive) will be randomized in a 1:1 ratio to a single dose level of ACI-35.030 or placebo and administered as intramuscular injections for a maximum of 4 years. The primary endpoint will measure cognitive decline as assessed by the Preclinical AD Cognitive Composite 5 (PACC-5) score, which combines tests that evaluate episodic memory, timed executive function, and global cognition. It is sensitive enough to detect early changes in cognitive function, even before the first clinical signs of mild cognitive impairment (MCI) are apparent2. The key secondary efficacy endpoint will assess the effect of ACI-35.030 on the propagation and/or accumulation of Tau pathology compared with placebo, as measured by Tau PET imaging in the Tau Naïve Composite region of interest. PET imaging for pathological Tau will be performed at baseline and annually for 4 years. This endpoint may be sufficient for a Biologics License Application (BLA) filing seeking accelerated approval from the U.S. Food & Drug Administration (FDA), with the primary endpoint serving as the basis for a traditional approval. Donohue MC, Sperling RA, Salmon DP, Rentz DM, Raman R, Thomas RG, Weiner M, Aisen PS, Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing, Alzheimer’s Disease Neuroimaging Initiative, and Alzheimer’s Disease Cooperative Study (2014) The preclinical Alzheimer cognitive composite: measuring amyloid-related decline. JAMA Neurol 71(8):961–970. https://doi.org/10.1001/jamaneurol.2014.803 ACI-35.030 (JNJ-64042056) is an investigational active immunotherapy designed using AC Immune’s SupraAntigen® platform. Its liposomal formulation incorporates a conformationally-constrained, membrane bound target peptide antigen, phosphorylated Tau (pTau), in addition to adjuvants and non-Tau T-helper peptides. Immunization with ACI-35.030 has been shown in a recent Phase 1b/2a clinical trial to rapidly elicit antibodies after the first injection against extracellular pathological pTau in 100% of elderly patients with Alzheimer’s disease. Importantly, the antibody response was sustained, boostable, and focused on pathological pTau, including enriched paired helical filaments (ePHF). Aggregation of pTau leads to the formation of neurotoxic ePHF and Tau tangles. Antibodies against non-phosphorylated Tau diminished over time. To date, no safety or tolerability issues have been observed following ACI-35.030 immunization. AC Immune’s clinically validated SupraAntigen® platform uses proprietary liposomes to rapidly generate novel product candidates for active immunotherapy as well as best-in-class monoclonal antibodies for passive immunization against key neurodegenerative disease targets. Antibodies generated by the platform are highly specific for the pathological conformations of misfolded proteins and have shown strong safety. The SupraAntigen® platform has successfully generated two active immunotherapies and two antibody candidates that have been validated in clinical studies and has led to multiple global partnerships with world-leading pharmaceutical companies. In addition to targeting Amyloid-beta and Tau, AC Immune has generated conformation-specific antibodies against emerging neurodegenerative disease targets including alpha-synuclein, TDP-43, and the NLRP3 inflammasome pathway. AC Immune SA is a clinical-stage biopharmaceutical company that aims to become a global leader in precision medicine for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features ten therapeutic and three diagnostic candidates, five of which are currently in Phase 2 clinical trials and one of which is in Phase 3. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies including Genentech, a member of the Roche Group, Eli Lilly and Company, and others, resulting in substantial non-dilutive funding to advance its proprietary programs and >$3 billion in potential milestone payments. The content above comes from the network. if any infringement, please contact us to modify.