ARGX-119 for ALS (ReALiSe Trial)
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: argenx
Prior Safety Data
Trial Summary
What is the purpose of this trial?This study aims to evaluate the safety of ARGX-119 in adults with ALS. The study will also assess the impact of ARGX-119 on ALS disease outcomes, including muscle function. The study consists of 2 periods: a treatment period when participants will receive one of three ARGX-119 doses or placebo and an extension period when all participants will receive the same dose of ARGX-119. Participation in the study will last up to approximately 100 weeks.
Is the drug ARGX-119 a promising treatment for ALS?The information provided does not directly mention ARGX-119 or its effects on ALS, so we cannot determine if it is a promising treatment based on this data.234610
Do I have to stop taking my current medications for the ARGX-119 ALS trial?The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the study coordinators for more details.
What safety data exists for ARGX-119 in ALS treatment?The provided research does not contain specific safety data for ARGX-119 or its use in ALS treatment. The studies focus on adverse drug reactions and databases for various drugs, but ARGX-119 is not mentioned. Further investigation into clinical trial registries or specific studies on ARGX-119 would be needed to find relevant safety data.18111215
What data supports the idea that ARGX-119 for ALS is an effective drug?The available research does not provide specific data on the effectiveness of ARGX-119 for ALS. However, it mentions other treatments like AMX0035 and GM604, which have shown some positive results in slowing ALS progression and improving certain functions. For example, GM604 slowed functional decline and improved biomarkers in a small study. Without specific data on ARGX-119, we can't compare its effectiveness to these other treatments.5791314
Eligibility Criteria
This trial is for adults aged 18 to 80 with ALS, who have a specific risk profile and at least 60% normal lung function. It's open to those with familial or sporadic ALS as per Gold Coast criteria.Inclusion Criteria
I am between 18 and 80 years old.
I have been diagnosed with ALS.
Participant Groups
The study tests ARGX-119's safety and its effect on muscle function in ALS patients. Participants will receive either ARGX-119 or a placebo during the treatment period, followed by an extension where all get ARGX-119.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: ARGX-119 - Dose 3Experimental Treatment1 Intervention
Participants will receive third dosage level of ARGX-119 intravenously during the double blinded treatment period followed by ARGX-119 in active treatment extension period
Group II: ARGX-119 - Dose 2Experimental Treatment1 Intervention
Participants will receive second dosage level of ARGX-119 intravenously during the double blinded treatment period followed by ARGX-119 in active treatment extension period
Group III: ARGX-119 - Dose 1Experimental Treatment1 Intervention
Participants will receive first dosage level of ARGX-119 intravenously during the double blinded treatment period followed by ARGX-119 in active treatment extension period
Group IV: PlaceboPlacebo Group2 Interventions
Participants will receive placebo intravenously during the double-blinded treatment period followed by ARGX-119 in active treatment extension period
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Montreal Neurological Institute and HospitalMontreal, Canada
Kaye Edmonton ClinicEdmonton, Canada
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Who is running the clinical trial?
argenxLead Sponsor
References
Drug Adverse Reaction Target Database (DART) : proteins related to adverse drug reactions. [2018]An adverse drug reaction (ADR) often results from interaction of a drug or its metabolites with specific protein targets important in normal cellular function. Knowledge about these targets is both important in facilitating the study of the mechanisms of ADRs and in new drug discovery. It is also useful in the development and testing of rational drug design and safety evaluation tools. The Drug Adverse Reaction Database (DART) is intended to provide comprehensive information about adverse effect targets of drugs described in the literature. Moreover, proteins involved in adverse effect targets of chemicals not yet confirmed as ADR targets are also included as potential targets. This database gives physiological function of each target, binding drugs/agonists/antagonists/activators/inhibitors, IC(50) values of the inhibitors, corresponding adverse effects, and type of ADR induced by drug binding to a target. Cross-links to other databases are also introduced to facilitate the access of information about the sequence, 3-dimensional structure, function, and nomenclature of each target along with drug/ligand binding properties, and related literature. The database currently contains entries for 147 ADR targets and 89 potential targets. A total of 187 adverse reaction conditions, 257 drugs, and 1080 ligands known to bind to each of these targets are also currently described. Each entry can be retrieved through multiple search methods including target name, target physiological function, adverse effect, ligand name, and biological pathways. A special page is provided for contribution of new or additional information. This database can be accessed at http://xin.cz3.nus.edu.sg/group/drt/dart.asp.
Mutation screening of the ALS2 gene in sporadic and familial amyotrophic lateral sclerosis. [2009]Mutations in the ALS2 gene cause juvenile-onset autosomal recessive amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia.
Variations in the coding and regulatory sequences of the angiogenin (ANG) gene are not associated to ALS (amyotrophic lateral sclerosis) in the Italian population. [2011]Potentially causative missense variations in the ANG gene and a positive association with the synonymous rs11701-G substitution was detected mainly in Irish and Scottish ALS patients. We screened 262 Italian SOD1 negative ALS patients (250 sporadic) and 415 matched controls for sequence variations in the coding, 3'/5' UTR and 5' flanking (642 bp) regions of the ANG gene. We identified 53 sequence variations of which 46 new, 20 with a minor allele frequency (MAF) >or=0.01 and only three localised in the coding sequence, namely the missense I46V, identified in one patient and two controls, and the synonymous G86G and T97T corresponding to rs11701 and rs2228653. None of the detected SNPs or of their haplotypic combinations was significantly associated with ALS susceptibility or clinical features. In conclusion, we did not detect the association with rs11701-G or with any other newly detected variation in the ANG regulatory region. Furthermore we did not identify potentially causal mutations in the coding region.
ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics. [2022]Amyotrophic lateral sclerosis (ALS) is the commonest adult onset motor neuron disease, with a peak age of onset in the seventh decade. With advances in genetic technology, there is an enormous increase in the volume of genetic data produced, and a corresponding need for storage, analysis, and interpretation, particularly as our understanding of the relationships between genotype and phenotype mature. Here, we present a system to enable this in the form of the ALS Online Database (ALSoD at http://alsod.iop.kcl.ac.uk), a freely available database that has been transformed from a single gene storage facility recording mutations in the SOD1 gene to a multigene ALS bioinformatics repository and analytical instrument combining genotype, phenotype, and geographical information with associated analysis tools. These include a comparison tool to evaluate genes side by side or jointly with user configurable features, a pathogenicity prediction tool using a combination of computational approaches to distinguish variants with nonfunctional characteristics from disease-associated mutations with more dangerous consequences, and a credibility tool to enable ALS researchers to objectively assess the evidence for gene causation in ALS. Furthermore, integration of external tools, systems for feedback, annotation by users, and two-way links to collaborators hosting complementary databases further enhance the functionality of ALSoD.
Fixed dynamometry is more sensitive than vital capacity or ALS rating scale. [2017]Improved outcome measures are essential to efficiently screen the growing number of potential amyotrophic lateral sclerosis (ALS) therapies.
Astrocyte elevated gene-1 is a novel regulator of astrogliosis and excitatory amino acid transporter-2 via interplaying with nuclear factor-κB signaling in astrocytes from amyotrophic lateral sclerosis mouse model with hSOD1G93A mutation. [2019]AEG-1 has received extensive attention on cancer research. However, little is known about its roles in astrogliosis of Amyotrophic lateral sclerosis (ALS). In this study, we detected AEG-1 expression in hSOD1G93A-positive (mut-SOD1) astrocytes and wild type (wt-SOD1) astrocytes, and intend to elucidate its potential functions in ALS related astrogliosis and the always accompanied dysregulated glutamate clearance. Results showed elevated protein and mRNA levels of AEG-1 in mut-SOD1 astrocytes; Also, NF-κB signaling pathway related proteins and inflammatory cytokines were upregulated in mut-SOD1 astrocytes; AEG-1 knockdown attenuated astrocytes proliferation and pro-inflammatory release; also we found that AEG-1 silence inhibited translocation of p65 from cytoplasma to nuclear, which was associated with inhibited NF-κB signaling. Besides, excitatory amino acid transporter-2 (EAAT2) expression levels were significantly decreased, accompanied by impaired glutamate clearance ability, in mut-SOD1 astrocytes; yin yang 1 (YY1), a transcriptional inhibitor for EAAT2, increased in nucleus of mut-SOD1 astrocytes. AEG-1 silence inhibited translocation of YY1 to nucleus, increased EAAT2 expression levels, and enhanced astrocytic ability of glutamate clearance, ultimately exerted the neuronal protection. Findings from this study implicate potential function of AEG-1 in mut-SOD1 related astrogliosis and the accompanied excitatory cytotoxic mechanism in ALS.
A Phase 2A randomized, double-blind, placebo-controlled pilot trial of GM604 in patients with Amyotrophic Lateral Sclerosis (ALS Protocol GALS-001) and a single compassionate patient treatment (Protocol GALS-C). [2023]Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options. Genervon has discovered and developed GM604 (GM6) as a potential ALS therapy. GM6 has been modeled upon an insulin receptor tyrosine kinase binding motoneuronotrophic factor within the developing central nervous system. Methods This was a 2-center phase 2A, randomized, double-blind, placebo-controlled pilot trial with 12 definite ALS patients diagnosed within 2 years of disease onset. Patients received 6 doses of GM604 or placebo, administered as slow IV bolus injections (3x/week, 2 consecutive weeks). Objectives were to assess the safety and efficacy of GM604 based on ALSFRS-R, FVC and selected biomarkers (TDP-43, Tau and SOD1, pNFH). This report also includes results of compassionate treatment protocol GALS-C for an advanced ALS patient. Results Definite ALS patients were randomized to one of two treatment groups (GM604, n = 8; placebo, n = 4). 2 of 8 GM604-treated patients exhibited mild rash, but otherwise adverse event frequency was similar in treated and placebo groups. GM604 slowed functional decline (ALSFRS-R) when compared to a historical control (P = 0.005). At one study site, a statistically significant difference between treatment and control groups was found when comparing changes in respiratory function (FVC) between baseline and week 12 (P = 0.027). GM604 decreased plasma levels of key ALS biomarkers relative to the placebo group (TDP-43, P = 0.008; Tau, P = 0.037; SOD1, P = 0.009). The advanced ALS patient in compassionate treatment demonstrated improved speech, oral fluid consumption, mouth suction with GM604 treatment and biomarker improvements. Conclusions We observed favorable shifts in ALS biomarkers and improved functional measures during the Phase 2A study as well as in an advanced ALS patient. Although a larger trial is needed to confirm these findings, the present data are encouraging and support GM604 as an ALS drug candidate.
Analyses of Adverse Drug Reactions-Nationwide Active Surveillance Network: Canadian Pharmacogenomics Network for Drug Safety Database. [2020]Adverse drug reactions (ADRs) are a major problem in modern medicine, representing up to the fourth-highest cause of mortality. Pharmacogenomic tests are 1 of the most promising methods to tackle the challenge of ADRs. The objective of this study was to analyze the clinical and demographic information of the pan-Canadian active surveillance network, Canadian Pharmacogenomics Network for Drug Safety (CPNDS). Information entered into the database by trained active surveillors between May 15, 2005 and May 9, 2017 was collected and analyzed. Specific data included for analysis were number of ADR reports, reports of drug use without ADRs, date of onset of ADR, suspected drugs, concomitant drugs, and fatal ADR cases. The CPNDS database consisted of 93,974 reports of medication use, including 10,475 reports of ADRs, of which 72.6% occurred in pediatric patients (≤21 years old). Self-reported ancestries were predominantly Europe (38.2%), Canada (9.6%), and East Asia (4.9%). The 5 most frequent ADRs were cutaneous ADRs, peripheral neuropathy, cardiotoxicity, central nervous system toxicity, and ototoxicity. The 5 drugs most commonly suspected to cause ADRs were methotrexate, vincristine, doxorubicin, cisplatin, and L-asparaginase. The CPNDS database is a valuable resource to identify clinical and genomic predictors of ADRs. The database also highlights our candidate ADRs for pharmacogenomic discovery research to identify additional ADR biomarkers. Additionally, the database provides information that can be used for developing strategies to prevent ADRs and raises awareness of ADRs among Canadian healthcare professionals.
Development and Validation of the Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS). [2021]A new outcome measure for overall disability level with improved responsiveness is needed for amyotrophic lateral sclerosis (ALS) clinical trials.
Clinical and Molecular Aspects of Senataxin Mutations in Amyotrophic Lateral Sclerosis 4. [2021]To determine the clinical and molecular features in patients with amyotrophic lateral sclerosis 4 (ALS4) due to mutations in the senataxin (SETX) gene and to develop tools for evaluating SETX variants.
Adverse events related to radium-223 treatment: "real-life" data from the Eudra-Vigilance database. [2021]The aim of our study was to analyze adverse events (AEs) associated with radium-223 using real life data from Eudra-Vigilance (EV) database.
Signal detection of botulinum toxin type A (BoNT/A) using the Korea Adverse Event Reporting System Database, 1999 - 2016. [2021]To detect signals of potential adverse events (AEs) after botulinum toxin (BTX) treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD).
MN-166 (ibudilast) in amyotrophic lateral sclerosis in a Phase IIb/III study: COMBAT-ALS study design. [2022]Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with motor neuron loss as a defining feature. Despite significant effort, therapeutic breakthroughs have been modest. MN-166 (ibudilast) has demonstrated neuroprotective action by various mechanisms: inhibition of proinflammatory cytokines and macrophage migration inhibitory factor, phosphodiesterase inhibition, and attenuation of glial cell activation in models of ALS. Early-phase studies suggest that MN-166 may improve survival outcomes and slow disease progression in patients with ALS. This article describes the rationale and design of COMBAT-ALS, an ongoing randomized, double-blind, placebo-controlled, multicenter Phase IIb/III study in ALS. This study is designed to evaluate the pharmacokinetics, safety and tolerability and assess the efficacy of MN-166 on function, muscle strength, quality of life and survival in ALS.
Incorporating patient preferences and burden-of-disease in evaluating ALS drug candidate AMX0035: a Bayesian decision analysis perspective. [2023]Label="OBJECTIVE">Provide US FDA and amyotrophic lateral sclerosis (ALS) society with a systematic, transparent, and quantitative framework to evaluate the efficacy of the ALS therapeutic candidate AMX0035 in its phase 2 trial, which showed statistically significant effects (p-value 3%) in slowing the rate of ALS progression on a relatively small sample size of 137 patients.
Neurotoxicity induced by taxane-derived drugs: analysis of the FAERS database 2017-2021. [2023]Taxane-related neurotoxicity is a frequent clinical problem but lacks postmarketing data regarding neurological disorders. This study aimed to evaluate the potential association between neurological adverse events and several taxanederived drugs via the Food and Drug Administration Adverse Event Reporting System (FAERS).