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Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus

ABSTRACT: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus

PROVIDER: PRJNA391720 | ENA |

REPOSITORIES: ENA

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Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus [blood]

Project description:This is a phase I randomized, double-blind, placebo-controlled crossover study which sought to evaluate a single dose of AMG 811, an anti-IFNγ antibody, in patients with DLE. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein

2017-06-23 | GSE100430 | GEO

Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus [skin]

2017-06-23 | GSE100093 | GEO

Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-06-23 | GSE100431 | GEO

Brief Report: Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus.

Project description:ObjectiveInterferon-γ (IFNγ) is implicated in the pathogenesis of discoid lupus erythematosus (DLE). This study sought to evaluate a single dose of AMG 811, an anti-IFNγ antibody, in patients with DLE.MethodsThe study was designed as a phase I randomized, double-blind, placebo-controlled crossover study of the pharmacodynamics, safety, and clinical efficacy of AMG 811 in patients with DLE. Patients received a single subcutaneous dose of AMG 811 (180 mg) or placebo. The patients in sequence 1 received AMG 811 followed by placebo, while those in sequence 2 received placebo followed by AMG 811. Pharmacodynamic end points included global transcriptional analyses of lesional and nonlesional skin, IFNγ blockade signature (IGBS) transcriptional scores in the skin and blood, keratinocyte IFNγ RNA scores, and serum levels of CXCL10 protein. Additional end points were efficacy outcome measures, including the Cutaneous Lupus Erythematosus Disease Area and Severity Index, and safety outcome measures.ResultsSixteen patients with DLE were enrolled in the study (9 in sequence 1 and 7 in sequence 2). AMG 811 treatment reduced the IGBS score (which was elevated in DLE patients at baseline) in both the blood and lesional skin. The keratinocyte IFNγ RNA score was not affected by administration of AMG 811. Serum CXCL10 protein levels (which were elevated in the blood of DLE patients) were reduced with AMG 811 treatment. The AMG 811 treatment was well tolerated but did not lead to statistically significant improvements in any of the efficacy outcome measures.ConclusionAMG 811 treatment led to changes in IFNγ-associated biomarkers and was well tolerated, but no significant clinical benefit was observed in patients with DLE.

| S-EPMC5434930 | biostudies-literature

Transcription profiling of rat tissues dosed with AMG A or AMG B

Project description:To evaluate and characterize gene expression changes and toxicity following oral gavage administration of AMG A & AMG B in male Sprague Dawley rats. Experiment Overall Design: This toxicogenomics study is designed to determine the toxicity and gene expression of AMG A and AMG B dosed orally daily (AMG A at 0mg/kg, 3mg/kg and 30 mg/kg and AMG B at 0mg/kg, 3mg/kg and 60mg/kg) for 1, 4 and 14 days. These doses are expected to produce mild and moderate changes in clinical pathology and histology associated with the pharmacologic antiangiogenic effect.

2008-06-11 | E-GEOD-10015 | biostudies-arrayexpress

Blockade of interferon-Î³ normalizes IFN regulated gene expression in subjects with systemic lupus erythematosus (SLE)

Project description:Normal donor blood was incubated with or without IFN-g stimulation to establish an IFN-g gene signature. Systemic lupus erythematosus subjects were treated with placebo or AMG 811, a therapeutic anti-IFN--g antibody, and changes in the IFN--g signature in whole blood of these subjects was measured. Blood from healthy volunteers (n=4) was collected into sodium heparin tubes, and then untreated or treated with 294 pM recombinant human IFN-Î³ for 0, 24, or 48 hours with incubation at 37oC, 5 % CO2. The blood was then added to PAXgene tubes and processed for RNA purification. Twenty six subjects with stable, mild to moderate SLE were administered placebo or a single dose of AMG 811 ranging from 2 mg to 180 mg SC or 60 mg IV. Whole blood PAXgene tube samples were collected from all cohorts at baseline, day-1 (pre-dose), and at days 15, 56, and end of study (EOS) after treatment Arrays were hybridized in a Loop design.

2016-02-24 | E-GEOD-78193 | biostudies-arrayexpress

Safety, pharmacokinetics and pharmacodynamics of AMG 811, an anti-interferon-γ monoclonal antibody, in SLE subjects without or with lupus nephritis.

Project description:ObjectiveTo evaluate safety, pharmacokinetics and pharmacodynamics of anti-interferon (IFN)-γ monoclonal antibody AMG 811 in subjects with SLE without or with lupus nephritis (LN).MethodsIn this phase Ib, randomised, multiple-dose escalation study (NCT00818948), subjects without LN were randomised to subcutaneous AMG 811 (6, 20 or 60 mg) or placebo and subjects with LN were randomised to subcutaneous AMG 811 (20, 60 or 120 mg) or placebo every four weeks for three total doses. Outcomes included incidence of adverse events (AEs); pharmacokinetics; levels of serum proteins (CXCL-10, interleukin 18, monocyte chemotactic protein-1); changes in gene transcript profiles and clinical parameters (Safety of Estrogen in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores, proteinuria, anti-double-stranded DNA (anti-dsDNA) antibodies, C3 complement, C4 complement).ResultsFifty-six subjects enrolled (28 SLE without LN; 28 with LN). Baseline mean SELENA-SLEDAI scores were 2.2 and 12.0 for SLE subjects without and with LN, respectively. Most subjects reported an AE; no meaningful imbalances were observed between AMG 811 and placebo. Pharmacokinetic profiles were similar and mostly dose-proportional in subjects without or with LN. AMG 811 treatment reduced CXCL-10 protein levels and blood-based RNA IFN-γ Blockade Signature compared with placebo. Reductions were less pronounced and not sustained in subjects with LN, even at the highest dose tested, compared with subjects without LN. No effect on SELENA-SLEDAI scores, proteinuria, C3 or C4 complement levels, or anti-dsDNA antibodies was observed.ConclusionAMG 811 demonstrated favourable pharmacokinetics and acceptable safety profile but no evidence of clinical impact. IFN-γ-associated biomarkers decreased with AMG 811; effects were less pronounced and not sustained in LN subjects.Trial registration numberNCT00818948; results.

| S-EPMC5604705 | biostudies-literature

Transcriptome of discoid lupus erythematosus (DLE) skin

Project description:Transcriptome of discoid lupus erythematosus (DLE) skin

| PRJNA494590 | ENA

Blockade of interferon-γ normalizes IFN regulated gene expression in subjects with systemic lupus erythematosus (SLE)

2016-02-24 | GSE78193 | GEO

Homo sapiens

Project description:Pharmacodynamics, Safety, and Clinical Efficacy of AMG 811, a Human Anti-Interferon-γ Antibody, in Patients With Discoid Lupus Erythematosus [skin]

| PRJNA390658 | ENA

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