A5013642414- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Adenosine and Purinergic Signaling
- Blood groups and transfusion
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Hormonal Regulation and Hypertension
- Blood Pressure and Hypertension Studies
- Asthma and respiratory diseases
- Neonatal Health and Biochemistry
- Inhalation and Respiratory Drug Delivery
- Peripheral Neuropathies and Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Antibiotics Pharmacokinetics and Efficacy
- Myasthenia Gravis and Thymoma
- Pharmacogenetics and Drug Metabolism
- Poisoning and overdose treatments
- Chronic Lymphocytic Leukemia Research
- Analytical Methods in Pharmaceuticals
- Multiple Sclerosis Research Studies
- Biosimilars and Bioanalytical Methods
- Adrenal Hormones and Disorders
- Eicosanoids and Hypertension Pharmacology
- Respiratory and Cough-Related Research
- COVID-19 Impact on Reproduction
- Calcium signaling and nucleotide metabolism
Alexion Pharmaceuticals (United States)
2018-2024
AstraZeneca (United States)
2022-2024
Alexion Pharma (Switzerland)
2022-2023
AstraZeneca (Brazil)
2022-2023
RELX Group (United States)
2020
Palmetto Hematology Oncology
2019
Allergan (India)
2015
Forest Research Institute
2012-2015
Allergan (United States)
2015
City of Knowledge
2014
Ravulizumab is a long-acting C5 inhibitor engineered from eculizumab with increased elimination half-life, allowing an extended dosing interval two to eight weeks. Here we evaluate the efficacy and safety of ravulizumab in adults atypical hemolytic uremic syndrome presenting thrombotic microangiopathy. In this global, phase 3, single arm study complement inhibitor-naïve (18 years older) who fulfilled diagnostic criteria for syndrome, enrolled patients received through 26-week initial...
Eculizumab is first-line treatment for paroxysmal nocturnal hemoglobinuria (PNH); however, approximately 11%-27% of patients may experience breakthrough hemolysis (BTH) on approved doses eculizumab. Ravulizumab, a new long-acting C5 inhibitor with four-times longer mean half-life than eculizumab, provides immediate, complete, and sustained inhibition over 8-week dosing intervals. In two phase 3 studies, ravulizumab was noninferior to eculizumab (Pinf ≤0.0004) the BTH endpoint; fewer...
Abstract Introduction The terminal complement C5 inhibitor ravulizumab has a long elimination half-life, allowing maintenance dosing every 8 weeks. In the 26-week, double-blind, randomized, placebo-controlled period (RCP) of CHAMPION MG study, provided rapid and sustained efficacy was well tolerated in adults with anti-acetylcholine receptor antibody-positive (AChR Ab+) generalized myasthenia gravis (gMG). This analysis evaluated pharmacokinetics (PK), pharmacodynamics (PD), potential...
Ravulizumab, a long-acting complement C5 inhibitor engineered from eculizumab, allows extending maintenance dosing every 2–3 weeks to 4–8 depending on bodyweight. Here, we evaluated the efficacy and safety of ravulizumab in inhibitor-naïve children (under 18 years) with atypical hemolytic uremic syndrome. In this phase III, single-arm trial, was administered eight patients 20 kg over, four under kg. The primary endpoint complete thrombotic microangiopathy response (normalization platelet...
Abstract Background Atypical hemolytic uremic syndrome (aHUS) is a rare, complement-mediated disease associated with poor outcomes if untreated. Ravulizumab, long-acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for the treatment of aHUS. Here, we report from pediatric patient cohort ravulizumab clinical trial (NCT03131219) who were switched chronic treatment. Methods Ten patients received loading dose on Day 1, followed by maintenance...
Abstract Ravulizumab, a novel long‐acting complement component 5 (C5) inhibitor administered every 8 weeks (q8w), was non‐inferior to eculizumab for all efficacy outcomes in two randomised, open‐label, phase 3 trials C5 inhibitor‐naïve (Study 301) and eculizumab‐experienced 302) adult patients with paroxysmal nocturnal haemoglobinuria (PNH). This pre‐specified analysis characterised ravulizumab pharmacokinetics (PK), pharmacodynamics (PD; free levels), PD differences between medications 301,...
Objective To assess the pharmacokinetics and pharmacodynamics of long-acting terminal complement 5 (C5) inhibitor ravulizumab in adults with anti-aquaporin-4 antibody-positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) phase 3, open-label CHAMPION-NMOSD trial (NCT04201262). Methods Patients aged 18 years or older received a weight-based intravenous loading dose (2,400–3,000 mg) on day 1, followed by maintenance doses (3,000–3,600 15 once every 8 weeks thereafter. Pharmacokinetic...
Ravulizumab, the only long-acting complement C5 inhibitor for adults with paroxysmal nocturnal hemoglobinuria (PNH), demonstrated non-inferiority to eculizumab after 26 weeks of treatment in inhibitor-naïve patients during a phase III randomized controlled trial. We present open-label extension results up 52 treatment.Patients assigned ravulizumab every 8 (q8w) or 2 primary evaluation period received q8w 26-week extension. Efficacy endpoints were lactate dehydrogenase (LDH) normalization,...
Abstract Ravulizumab every 8 weeks showed non‐inferiority to eculizumab 2 in a 26‐week, phase 3, randomized controlled trial adults with paroxysmal nocturnal hemoglobinuria (PNH) who were clinically stable on (NCT03056040). We report results from the first 26 of extension period which patients continued ravulizumab (n = 96) or switched 95). At week 52, mean (SD) lactate dehydrogenase levels increased 8.8% (29%) ravulizumab‐ravulizumab and 5.8% (27%) eculizumab‐ravulizumab primary evaluation...
This study compared the pharmacokinetics (PK) of ravulizumab on-body delivery system for subcutaneous (SUBQ) administration with intravenous (IV) in eculizumab-experienced patients paroxysmal nocturnal hemoglobinuria (PNH). Patients PNH received SUBQ (n = 90) or IV 46) during 10-week randomized treatment period; all then an extension period (< 172 weeks; data cutoff 1 year). Primary endpoint was day 71 serum trough concentration (Ctrough). Secondary endpoints were Ctrough and free C5 over...
Drug interactions are a significant clinical concern, particularly in patients with conditions such as heart disease and hypertension, whom coadministration of multiple drugs is common. Nebivolol selective β1-blocker vasodilatory properties approved for the treatment hypertension. Drug-drug were investigated when nebivolol was coadministered to subjects classified poor CYP2D6 metabolizers extensive who receiving other commonly administered hypertension or compounds metabolized by cytochrome...
Terminal complement amplification is hypothesized to be a key contributor the clinical manifestations of severe coronavirus disease 2019 (COVID-19). Ravulizumab, humanized monoclonal antibody that binds with high affinity protein C5 and inhibits terminal activation, being evaluated as treatment for COVID-19-related pneumonia, acute lung injury, respiratory distress syndrome in an ongoing phase 3 randomized controlled trial (ALXN1210-COV-305). To address overactivation COVID-19 compared...
We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals.Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had with bilateral pulmonary infiltrates oxygen requirement. Eculizumab was administered on day 1...
Combining different classes of antihypertensives is more effective for reducing blood pressure (BP) than increasing the dose monotherapies. The aims this phase I study were to investigate pharmacokinetic and pharmacodynamic interactions between nebivolol, a vasodilatory β1-selective blocker, valsartan, an angiotensin II receptor assess safety tolerability combination. This was single-center, randomized, open-label, multiple-dose, 3-way crossover trial in 30 healthy adults aged 18–45 years....
Aclidinium bromide is a long-acting muscarinic antagonist in development for chronic obstructive pulmonary disease treatment. This 2-part, phase I study evaluated the safety and tolerability of single ascending intravenous (IV) doses aclidinium to determine its maximum tolerated dose (MTD; part I) absolute bioavailability (part II). Healthy male participants (N = 24) were randomized (1:1) each part: 3-period crossover, placebo-controlled, single-ascending, alternating IV (25-400 µg) 2-period...
ABSTRACT Aclidinium bromide is a novel, inhaled long‐acting muscarinic antagonist with low systemic activity developed for the treatment of COPD. It an ester compound rapidly hydrolysed in plasma into inactive alcohol and acid metabolites. In this Phase I, open‐label study, rates routes elimination radioactivity following intravenous administration [ 14 C]‐aclidinium were determined. The metabolites aclidinium also characterized identified excreta. Twelve healthy males randomized (1:1) to...