Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Initial Efficacy of ASK8007 in Comparison With Placebo in Patients With Active Rheumatoid Arthritis - a Randomized, Double Blind, Placebo-controlled, Combined Single Dose Escalation and Multiple Dose Study

The purpose of this study is to investigate the safety and tolerability of the new medication ASK8007, and to study whether it has a beneficial effect on joint inflammation in patients with rheumatoid arthritis.

开始日期2007-09-01

申办/合作机构

Astellas Pharma, Inc.

100 项与 ASK-8007 相关的临床结果

登录后查看更多信息

100 项与 ASK-8007 相关的转化医学

登录后查看更多信息

100 项与 ASK-8007 相关的专利（医药）

登录后查看更多信息

项与 ASK-8007 相关的文献（医药）

2022-08-01·Current Medicinal Chemistry

Osteopontin in CardioMetabolic Medicine: A Risk Stratification Biomarker with Future Therapeutic Implication

作者: Carbone, Federico ; Montecucco, Fabrizio

Obesity is no longer viewed as single entity but rather as a heterogene ous disease with different phenotypes: classical, metabolically healthy, normal weight and osteosarcopenic obesity [2].Those phenotypes overwhe lm traditional characterization by BMI, but they are rather an e xpression of the new emerging paradigm of CardioMetabolic risk: a cluster of visceral fat deposition (also referred to as adiposopathy) , ectopic fat depots, insulin resistance and cytokine/ adi- pokines dysregulation [3].In line with this new view, proving the central role of inflammation would give an integrated perspective on globa l CardioMetabolic risk finally linked to the established concept of vulnerable patient.Out of the bone, macrophages represent the major source of OPN and one of the main targets.The expression of OPN is up- regulated during injury/healing processes when it is deeply involved in inflammation, fi brosis, mineralization, and tissue regeneration. OPN gene expression is tightly regulat ed by a wide range of hormone s, growth factors, cytokines, and drugs.Furt hermore, epigenetic control of OPN expression also exists. H3K9a, H3K27ac, or H3K4 have been reported to upre gulate OPNc expression in at herosclerosis and diabetes. Conversely, less is known about the epigene tic control of the OPN precursor Spp1.However, only one human antibody inhibit- ing both the RGD domain as well as the α9β1 integrin-d ependent cell binding to OPN (ASK8007) has been so far tested in a proof-of-concept study involving patients with rh eumatoid arthritis without clin. improvement.A consensus on these issues might finally clarify potential therap eutic implications of OPN m odulation at several levels ranging from lifestyle modifi- cations, pharmacotherapy, and ev en surgical interventions.

2012-02-01·Annals of the Rheumatic Diseases1区 · 医学

Safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of the monoclonal antibody ASK8007 blocking osteopontin in patients with rheumatoid arthritis: a randomised, placebo controlled, proof-of-concept study

1区 · 医学

Article

作者: M den Adel ; J G A Houbiers ; E Brouwer ; Hilde Jacobs ; D M Gerlag ; J Isaacs ; G M Holtkamp ; M J H Boumans ; H Ishikura ; Patrick Verschueren ; J Gomez-Reino ; B Rojkovich ; Rene Westhovens ; P P Tak ; S Kelly ; A Hastings

OBJECTIVESOsteopontin is an extracellular matrix protein with diverse immunomodulatory functions. The authors assessed the safety, tolerability, pharmacokinetics, pharmacodynamics and initial efficacy of the humanised monoclonal antibody ASK8007, which blocks osteopontin.METHODSIn this double-blind, multicentre, combined first-in-man, single-dose escalation (phase I, part A) and proof-of-concept, multiple-dose (phase IIA, part B) study, rheumatoid arthritis (RA) patients with active disease were randomly assigned to receive ASK8007 or placebo intravenously. Safety monitoring, pharmacokinetic and pharmacodynamic analyses and clinical assessments were performed throughout the study. The expression of phenotypic cell markers was evaluated in synovial tissue biopsy samples obtained at baseline and 43 days after initiation of treatment (part B) by immunohistochemistry and digital image analysis. Two co-primary efficacy endpoints were the change from baseline in the disease activity score evaluated in 28 joints (DAS28) and the change from baseline in the number of CD68 synovial sublining macrophages, both assessed on day 43 (part B).RESULTSASK8007 was overall safe and well tolerated up to the highest studied dose (20 mg/kg). Quantifiable concentrations of ASK8007 were detected in synovial fluid. No differences were observed for changes from baseline in DAS28 and CD68 sublining macrophages between ASK8007 and placebo-treated patients. Within the ASK8007 treatment group, there were also no apparent clinical responses or changes in sublining macrophages. In addition, ASK8007 treatment did not change other assessed biomarkers.CONCLUSIONSOsteopontin blockade is well tolerated and not related to safety concerns. These results consistently show that osteopontin blockade is unlikely to induce robust clinical improvement in RA patients.

2007-11-01·International Immunopharmacology2区 · 医学

Successful treatment of collagen-induced arthritis in non-human primates by chimeric anti-osteopontin antibody

2区 · 医学

Article

作者: Toshihiro Nakashima ; Junko Morimoto ; Toshimitsu Uede ; Nobuchika Yamamoto ; Takeshi Naruse ; Masaharu Torikai ; Fumihiko Sakai ; Shigeyuki Kon

The presence of thrombin-cleaved form of osteopontin well correlated with various inflammatory disease activities in not only rodents, but also humans. We previously demonstrated that the blocking of the interaction of a cryptic epitope within osteopontin, which is exposed by thrombin cleavage, with its integrins by specific antibody recognizing cryptic epitope of mouse osteopontin, could significantly inhibits the development of arthritis in mice. We generated a murine monoclonal antibody, 2K1, specifically recognizing a cryptic epitope of human osteopontin, SVVYGLR. We constructed a chimeric antibody, C2K1 in which variable region of 2K1 was fused with human IgG1 constant region. In the present study, we investigated whether the therapeutic administration of C2K1 could ameliorate the established collagen-induced arthritis in cynomolgus monkey. Thus, C2K1 was injected after the onset of arthritis. The inhibition of joint swelling by C2K1 became evident at 4 to 5 weeks after initiation of arthritis, when blood level of C2K1 was peaked. Joint swelling reappeared along with the sharp decline of C2K1 blood levels at 6 weeks. Importantly, destruction of bone and cartilage in joints was still significantly prevented at 10 weeks when blood level of C2K1 was quite low if any and anti-C2K1 antibody emerged. These results demonstrate that neutralizing antibody against the cryptic epitope of osteopontin can be a future therapeutic choice for patients with rheumatoid arthritis.

100 项与 ASK-8007 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
骨病	临床2期	-	Immuno-Biological Laboratories Co., Ltd.	-
骨病	临床2期	-	Astellas Pharma, Inc.	-
骨病	临床2期	-	The Chemo-Sero-Therapeutic Research Institute	-
肿瘤	临床2期	日本	-	-
类风湿关节炎	临床2期	-	The Chemo-Sero-Therapeutic Research Institute	-
类风湿关节炎	临床2期	-	Immuno-Biological Laboratories Co., Ltd.	-
类风湿关节炎	临床2期	-	Immuno-Biological Laboratories Co., Ltd.	-
类风湿关节炎	临床2期	-	The Chemo-Sero-Therapeutic Research Institute	-