An Open-label, Multicenter, Phase 4 Study to Assess the Effects of a Prophylactic Immune Tolerizing Regimen in MPS II Treatment-Naïve Patients Planned to Receive ELAPRASE Who Are at Risk of Developing Persistent Neutralizing Antibodies

The main aim of this study is to evaluate the ability of a prophylactic immune tolerizing regimen (ITR) to prevent or reduce the development of high titer anti-idursulfase antibodies in treatment-naïve participants with Hunter syndrome.
In this open label, single arm study, all participants will receive ELAPRASE treatment and a prophylactic ITR.
Participants will be treated with ELAPRASE for up to 104 weeks. The prophylactic ITR will start 1 day prior to the start of ELAPRASE. The prophylactic ITR will consist of a 5-week cycle of: Rituximab (intravenously [IV], weekly for 4 weeks); Methotrexate (oral, 3 times per week for 5 weeks) and intravenous immunoglobulin (IVIG) (IV, every 4 weeks of the cycle).
Following the completion of 1 cycle, an assessment will be made at Month 6, 12, and 18 regarding the need for administering another 5-week cycle of the ITR.
Participants will be in the study for approximately 112 weeks (including 6 weeks for screening, up to 104 weeks for treatment, and 2 weeks for follow-up).

开始日期2023-02-28

申办/合作机构

Takeda Pharmaceutical Co., Ltd.

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100 项与 Hyaluronic acid x CD20 相关的临床结果

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100 项与 Hyaluronic acid x CD20 相关的转化医学

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0 项与 Hyaluronic acid x CD20 相关的专利（医药）

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项与 Hyaluronic acid x CD20 相关的文献（医药）

2020-01-01·Folia biologica4区 · 医学

Anti-CD38 Therapy with Daratumumab for Relapsed/Refractory CD20-Negative Diffuse Large B-Cell Lymphoma.

4区 · 医学

Article

作者: Pokorna, E ; Vokurka, M ; Klener, P ; Karolova, J ; Svaton, M ; Vockova, P

Diffuse large B-cell lymphoma (DLBCL) is the most common and one of the most aggressive subtypes of non-Hodgkin's lymphomas. Front-line therapy consists of chemotherapy in combination with anti-CD20 monoclonal antibody rituximab. Relapses after rituximab-based regimen have poor prognosis and call for new treatment options. Immunohistochemistry analysis of relapsed DLBCL often reveal CD20-negative lymphoma, which limits repeated use of rituximab in combination with salvage chemotherapy. CD38 is a surface antigen that binds to CD38, CD31/PECAM-1 and hyaluronic acid. CD38 is an important mediator of signal transmission from the microenvironment into the cell. Anti-CD38 monoclonal antibody daratumumab has been approved for the treatment of multiple myeloma. Expression of CD38 on the surface of DLBCL is highly variable (compared to strong expression on myeloma cells), but can be easily assessed by flow cytometry or immunohistochemistry. A patient-derived xenograft (PDX) model of CD20-negative, CD38-positive DLBCL derived from a patient with rituximab-refractory DLBCL was used for in vivo experiments. We demonstrated that daratumumab suppressed growth of subcutaneous PDX tumours significantly more effectively than rituximab. Analysis of tumours obtained from mice treated with daratumumab revealed down-regulation of surface CD38, suggesting endocytosis of CD38-daratumumab complexes. The results suggest a potential clinical use of daratumumab in combination with salvage chemotherapy in patients with relapses of CD20-negative DLBCL. In addition, daratumumab might potentially serve as a suitable antibody moiety for derivation of antibodydrug conjugates for the targeted delivery of toxic payloads to the lymphoma cells.

2019-05-01·Advanced Functional Materials1区 · 材料科学

Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles

1区 · 材料科学

Article

作者: Laccetti, Kristiana H. ; Hammond, Paula T. ; Correa, Santiago ; Dreaden, Erik ; Min, Jouha ; Roy, Sweta ; Roh, Young Hoon ; Palmer, Peter A. ; Kong, Stephanie ; Li, Jiahe ; Lawson, Edward C. ; Choi, Ki Young ; Heo, Roun

AbstractUsing siRNA therapeutics to treat hematologic malignancies has been unsuccessful because blood cancer cells exhibit remarkable resistance to standard transfection methods. Herein, the successful delivery of siRNA therapeutics with a dual‐targeted, layer‐by‐layer nanoparticle (LbL‐NP) is reported. The LbL‐NP protects siRNA from nucleases in the bloodstream by embedding it within polyelectrolyte layers that coat a polymeric core. The outermost layer consists of hyaluronic acid (a CD44‐ligand) covalently conjugated to CD20 antibodies. The CD20/CD44 dual‐targeting outer layer provides precise binding to blood cancer cells, followed by receptor‐mediated endocytosis of the LbL‐NP. This siRNA delivery platform is used to silence B‐cell lymphoma 2 (BCL‐2), a pro‐survival protein, in vitro and in vivo. The dual‐targeting approach significantly enhances internalization of BCL‐2 siRNA in lymphoma and leukemia cells, which leads to significant downregulation of BCL‐2 expression. Systemic administration of the dual‐targeted, siRNA‐loaded nanoparticle induces apoptosis and hampers proliferation of blood cancer cells, both in cell culture and in orthotopic non‐Hodgkin's lymphoma animal models. These results provide the basis for approaches to targeting blood‐borne cancers and other diseases and suggest that LbL nanoassemblies are a promising approach for delivering therapeutic siRNA to hematopoetic cell types that are known to evade transfection by other means.

2015-12-01·Annals of the Rheumatic Diseases1区 · 医学

B-cell depletion attenuates serological biomarkers of fibrosis and myofibroblast activation in IgG4-related disease

1区 · 医学

Article

作者: Mattoo, Hamid ; Carruthers, Mollie ; Feeney, Eoin ; Chung, Raymond T ; Kulikova, Maria ; Deshpande, Vikram ; Mahajan, Vinay ; Stone, John H ; Wallace, Zachary S ; Della-Torre, Emanuel ; Pillai, Shiv

ObjectivesFibrosis is a predominant feature of IgG4-related disease (IgG4-RD). B-cell depletion induces a prompt clinical and immunological response in patients with IgG4-RD, but the effects of this intervention on fibrosis in IgG4-RD are unknown. We used the enhanced liver fibrosis (ELF) score to address the impact of rituximab on fibroblast activation. The ELF score is an algorithm based on serum concentrations of procollagen-III aminoterminal propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid.MethodsTen patients with active, untreated IgG4-RD were enrolled. ELF scores were measured and correlated with the IgG4-RD Responder Index, serum IgG4, circulating plasmablasts and imaging studies. Through immunohistochemical stains for CD3, CD20, IgG4 and α-smooth muscle actin, we assessed the extent of the lymphoplasmacytic infiltration and the degree of fibroblast activation in one patient with tissue biopsies before and after rituximab.ResultsThe ELF score was increased in patients with IgG4-RD compared with healthy controls (8.3±1.4 vs 6.2±0.9; p=0.002) and correlated with the number of organs involved (R2=0.41; p=0.04). Rituximab induced significant reductions in the ELF score, the number of circulating plasmablasts and the IgG4-RD Responder Index (p<0.05 for all three parameters). Rituximab reduced both the lymphoplasmacytic infiltrate and myofibroblast activation. IgG4-RD relapse coincided with recurrent increases in the ELF score, indicating reactivation of collagen deposition.ConclusionsThe ELF score may be a clinically useful indicator of active fibrosis and the extent of disease in IgG4-RD. B-cell depletion has the potential to halt continued collagen deposition by attenuating the secretory phenotype of myofibroblasts in IgG4-RD lesions.