Efgartigimod for Myositis
(ALKIVIA Trial)
Recruiting in Palo Alto (17 mi)
+424 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: argenx
Disqualifiers: Active infection, Autoimmune disease, Malignancy, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing an injectable medication called efgartigimod PH20 SC in people with certain muscle inflammation diseases. The goal is to see if it helps improve their condition by lowering harmful proteins in their blood. The study focuses on patients with specific subtypes of these diseases who often don't respond well to usual treatments. Efgartigimod was developed for autoimmune diseases and has been approved for treating a specific muscle condition in adults.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but it mentions that participants must be on a permitted background treatment for idiopathic inflammatory myopathy. It's best to discuss your specific medications with the study team.
What data supports the effectiveness of the drug Efgartigimod for treating myositis?
Research shows that Efgartigimod can restore muscle function in a mouse model of immune-mediated necrotizing myopathy, a severe form of myositis. This suggests it may help reduce harmful antibodies and improve muscle function in similar conditions.
12345Is efgartigimod safe for humans?
Efgartigimod has been generally well tolerated in clinical trials for conditions like generalized myasthenia gravis, with most side effects being mild to moderate.
16789How is the drug Efgartigimod PH20 SC different from other treatments for myositis?
Efgartigimod PH20 SC is unique because it works by reducing harmful antibodies in the body through a mechanism that prevents their recycling, which is different from traditional treatments like intravenous immunoglobulin (IVIg) that mainly focus on modulating the immune response. This drug is administered subcutaneously (under the skin), offering a potentially more convenient option compared to the intravenous route of other therapies.
1341011Eligibility Criteria
Adults with active Idiopathic Inflammatory Myopathy (IIM), specifically dermatomyositis, immune-mediated necrotizing myopathy, or polymyositis including antisynthetase syndrome. Participants must have muscle weakness and abnormal enzyme levels indicating IIM. They should be on stable IIM treatments and use contraception if applicable. Exclusions include other primary causes of muscle weakness, severe infections like HIV/HBV/HCV, recent major surgery risks, drug abuse history, pregnancy/lactation intentions during the study period.Inclusion Criteria
Contraceptive use consistent with local regulations, where available, for individuals participating in clinical studies. Women of childbearing potential must have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline before receiving investigational medicinal product (IMP)
Abnormal levels of at least 1 of the following enzymes: creatine kinase (CK), aldolase, lactate dehydrogenase, aspartate aminotransaminase (AST), alanine aminotransferase (ALT), based on central laboratory results
I was diagnosed with dermatomyositis before I turned 18, and it was within the last 5 years.
+10 more
Exclusion Criteria
You have had an allergic reaction to the experimental medication or any of its ingredients.
You have another autoimmune disease that could make it difficult to accurately evaluate your symptoms of idiopathic inflammatory myopathy (IIM) or might put you at increased risk.
Positive serum test at screening for active viral infection with any of the following conditions: Hepatitis B virus (HBV); Hepatitis C virus (HCV); HIV
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive efgartigimod PH20 SC or placebo on top of background treatment
12 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing Efgartigimod PH20 SC's effectiveness compared to a placebo in improving symptoms of IIM as measured by Total Improvement Score (TIS). It includes adults diagnosed with certain subtypes of IIM who will receive either the investigational medication or a placebo while continuing their standard treatment for IIM.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: EFG PH20 SCExperimental Treatment1 Intervention
participants receiving efgartigimod PH20 SC on top of background treatment
Group II: PBO PH20 SCPlacebo Group1 Intervention
participants receiving placebo PH20 SC on top of background treatment
Efgartigimod PH20 SC is already approved in European Union, United States, Japan, China for the following indications:
🇪🇺 Approved in European Union as VYVGART for:
- Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive
🇺🇸 Approved in United States as VYVGART Hytrulo for:
- Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
🇯🇵 Approved in Japan as VYVDURA for:
- Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive
🇨🇳 Approved in China as Efgartigimod alfa injection (subcutaneous injection) for:
- Generalized myasthenia gravis in adults who are anti-acetylcholine receptor antibody positive
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Investigator site 08 - 0010180Denver, CO
Investigator site 06 - 0010122Phoenix, AZ
Investigator site 05 - 0010004Orange, CA
Investigator site 07 - 0010167Pittsburgh, PA
More Trial Locations
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Who Is Running the Clinical Trial?
argenxLead Sponsor
References
Efgartigimod restores muscle function in a humanized mouse model of immune-mediated necrotizing myopathy. [2023]Immune-mediated necrotizing myopathies (IMNMs) are severe forms of myositis often associated with pathogenic anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies (aAbs). Efgartigimod is an engineered human IgG1 Fc fragment that antagonizes the neonatal Fc receptor (FcRn), thereby preventing recycling and promoting lysosomal degradation of IgG, including aAbs. We evaluated the therapeutic effects of IgG reduction by efgartigimod in a humanized murine model of IMNM.
Clinical benefits and immunopathological correlates of intravenous immune globulin in the treatment of inflammatory myopathies. [2005]High-dose intravenous immune globulin (IVIG) is emerging as a promising therapy for patients with inflammatory myopathies who have become unresponsive to, or cannot tolerate, conventional therapies. In a double-blind, placebo-controlled study, using objective criteria for improvement, IVIG demonstrated moderate to dramatic improvement in 75% of the patients with dermatomyositis. Preliminary results from a controlled study in inclusion-body myositis show that IVIG may also exert a mild benefit, but only in a small number of patients and in certain muscle groups. In some patients with polymyositis, IVIG is reported to be of benefit but controlled studies have not yet been completed. Immunocytochemical, immunological and in vitro studies on the patients' repeated muscle biopsies and follow-up sera showed that IVIG exerts its action in inflammatory myopathies by: (i) inhibiting myotoxic cytokines, such as TNF-alpha and IL-1; (ii) blockade of Fc receptors on endomysial macrophages interfering with Fc receptor-mediated phagocytosis; and (iii) inhibiting the uptake of C3 and intercepting the formation and deposition of membranolytic attack complex on the endomysial capillaries.
Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. [2009]To investigate serum levels of B cell activating factor (BAFF) in patients with myositis and correlate these to autoantibody profile, clinical phenotype and treatment.
Intravenous immunoglobulin in patients with anti-GAD antibody-associated neurological diseases and patients with inflammatory myopathies: effects on clinicopathological features and immunoregulatory genes. [2018]Controlled trials with intravenous immunoglobulin (IVIg) were conducted in patients with Stiff-Person Syndrome (SPS) and dermatomyositis (DM), two humorally mediated neurological disorders, and in inclusion body myositis (IBM), a T-cell-mediated inflammatory myopathy. The clinical efficacy was compared with alterations on tissue expression of complement, cytokines, chemokines, adhesion molecules, and immunoregulatory genes. The following patients were randomized in three separate trials to receive IVIg or placebo for 3 mo: (a) 16 patients with anti-GAD antibody-positive SPS; (b) 15 patients with DM resistant to therapies; and (c) 19 patients with IBM. After a washout, they crossed to the alternative therapy for another 3 mo. Efficacy was based on the difference in the respective disease scores from baseline to the second and third month of the infusions. In patients with SPS and DM, the scores changed positively and significantly from months 1 through 3, but returned to baseline when the patients crossed to placebo. In contrast, the scores in the placebo-randomized group remained constant or worsened from months 1 to 3, but improved significantly after crossing to IVIg. The muscle scores of patients with IBM did not significantly change between IVIg or placebo. In SPS, the anti-GAD65 antibody titers declined after IVIg but not after placebo. In DM, there was reduction of complement consumption, interception of membranolytic attack complex formation, downregulation of inflammation, fibrosis, cytokines, chemokines and adhesion molecules, and alterations in thousands of immunoregulatory genes. We conclude that IVIg is a safe and effective therapy for patients with SPS and DM unresponsive to other agents. In tissues, IVIg restores tissue cytoarchitecture by suppressing the inflammatory mediators at the protein, mRNA, and gene level.
[Late phase II/III study of BYM338 in patients with sporadic inclusion body myositis (RESILIENT): Japanese cohort data]. [2022]A global, randomized, double-blind placebo-controlled study was conducted to confirm that BYM338 (bimagrumab), an anti-activin type II receptor antibody, improves motor function in patients with sporadic inclusion body myositis after 52 weeks' treatment consisting of intravenous administration every 4 weeks at doses of 10, 3, and 1 mg/kg. In a Japanese sub-population (20 patients in total, 5 per dose group), no significant differences in the change from baseline of the 6-minute walking distance at Week 52 (primary endpoint) were observed between the placebo group and each BYM338 dose group. Furthermore, the lean body mass as an indicator of skeletal muscle mass increased in all BYM338 groups compared with the placebo group and the effects were dose-dependent. Overall, the Japanese sub-population showed similar trends as observed in the entire population (251 patients in total).
Efgartigimod Alfa in Generalised Myasthenia Gravis: A Profile of Its Use. [2023]Intravenous efgartigimod alfa (also known as efgartigimod alfa-fcab in the USA; Vyvgart®) is the first neonatal Fc receptor antagonist approved in several countries worldwide, including the USA and EU for the treatment of generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody positive, and in Japan for the treatment of gMG regardless of antibody status. In the double-blind, placebo-controlled phase 3 ADAPT trial in patients with gMG, efgartigimod alfa significantly and rapidly reduced disease burden and improved muscle strength and quality of life compared with placebo. The clinical benefits of efgartigimod alfa were durable and reproducible. Furthermore, in an interim analysis of the ongoing open-label phase 3 ADAPT+ extension trial, efgartigimod alfa provided consistent clinically meaningful improvements in patients with gMG. Efgartigimod alfa was generally well tolerated, with most adverse events being mild to moderate in severity.
Efgartigimod: First Approval. [2022]Efgartigimod (efgartigimod alfa-fcab, Vyvgart™) is a first-in-class neonatal Fc receptor antagonist being developed by argenx for the treatment of autoimmune diseases including myasthenia gravis. In December 2021, intravenous efgartigimod received its first approval in the USA for the treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive. Intravenous efgartigimod has also been evaluated for generalized myasthenia gravis in various other countries, with the agent subsequently approved in Japan in January 2022 for generalized myasthenia gravis patients regardless of antibody status and in preregistration stage in the EU. Several clinical studies of intravenous and subcutaneous formulation of efgartigimod are also being investigated for other autoimmune diseases including bullous pemphigoid, chronic inflammatory demyelinating polyradiculoneuropathy, immune thrombocytopenia, autoimmune myositis and pemphigus. This article summarizes the milestones in the development of efgartigimod leading to this first approval for generalized myasthenia gravis.
Efgartigimod beyond myasthenia gravis: the role of FcRn-targeting therapies in stiff-person syndrome. [2023]Stiff-person syndrome (SPS) is a rare autoimmune neurological disorder characterized by high titers of antibodies against glutamic acid decarboxylase (GAD) causing impaired GABAergic inhibitory neurotransmission. To date, there is not a defined therapy for such condition, but immunomodulating therapies, such as plasma exchange, intravenous immunoglobulins, and rituximab, have been widely used in clinical practice. However, the efficacy and tolerability of these treatments is not well established. Efgartigimod, a new neonatal Fc receptor (FcRn) blocker, is a human IgG1 antibody Fc fragment engineered with increased affinity for FcRn binding, leading to a reduction in IgGs levels, including pathogenic IgG autoantibody showing promising results in neurological autoimmune disorders and has been approved for the treatment of AChR-seropositive generalized myasthenia gravis (MG). In this study, we report and describe the first data on treatment with efgartigimod in three patients affected by both AChR-seropositive generalized MG and anti-GAD-seropositive SPS. Patients were followed since the start of efgartigimod and for the whole treatment period (12 weeks). MG symptoms were assessed with the "MG activity of daily living score" and the Quantitative Myasthenia Gravis score, while SPS ones were assessed with the "SPS activity of daily living score"; muscle strength was assessed with the Medical Research Council Sum score; the overall disability from MG and SPS was assessed by the modified Rankin Scale. All patients showed an improvement in symptoms of both SPS and MG after 2 cycles of treatment. Our data suggest that efgartigimod may be considered as a candidate drug for SPS and other autoantibody-mediated neurological disorders.
Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. [2022]There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis.
A machine learning analysis to predict the response to intravenous and subcutaneous immunoglobulin in inflammatory myopathies. A proposal for a future multi-omics approach in autoimmune diseases. [2022]To evaluate the response to treatment with intravenous (IVIg) and subcutaneous (20%SCIg) immunoglobulin in our series of patients with Inflammatory idiopathic myopathies (IIM) by the means of artificial intelligence.
Limited effects of high-dose intravenous immunoglobulin (IVIG) treatment on molecular expression in muscle tissue of patients with inflammatory myopathies. [2022]The study was conducted with the aim of achieving an improved understanding of the molecular mechanisms of high-dose intravenous immunoglobulin (IVIG) in inflammatory myopathies by investigating the effects on muscle function and immunological molecules in skeletal muscle of polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM) patients.