Pharmacokinetics and Safety of Roledumab, a Fully Human Recombinant Monoclonal Anti-RhD Antibody, in RhD-negative Pregnant Woman Carrying an RhD-positive Foetus: a Phase IIb, Multicenter, Open-label Study

The aim of this study is to assess the pharmacokinetic profile of Roledumab 300μg IM / IV in RhD-negative pregnant women carrying an RhD-positive foetus.
To assess the safety of Roledumab in RhD-negative pregnant women and in RhD-positive fetus and newborns.
In addition the efficacy of Roledumab 300μg IM and IV to prevent RhD alloimmunisation in RhD-negative pregnant women carrying an RhD-positive fetus and the immunogenicity of Roledumab will be assessed.

Start Date01 Apr 2014

Sponsor / Collaborator

Laboratoire Français du Fractionnement et des Biotechnologies

EUCTR2009-011017-24-DE / Not yet recruitingNot Applicable

A Phase II, open-label, randomised, dose-finding study to compare the efficacy (in terms of clearance of RhD-positive RBCs) and safety of LFB-R593, a monoclonal anti-RhD antibody, vs Rhophylac®, a polyclonal anti-RhD immunoglobulin in healthy RhD negative volunteers

Start Date03 Aug 2009

Sponsor / Collaborator

LFB Biotechnologies SASU

NCT00952575 / CompletedPhase 2

A Phase II, Open-label, Randomised, Dose-finding Study to Compare the Efficacy (in Terms of Clearance of RhD-positive RBCs) and Safety of LFB-R593, a Monoclonal Anti-RhD Antibody vs a Polyclonal Anti-RhD Immunoglobulin in Healthy RhD Negative Volunteers

This phase II study is designed to demonstrate the ability of LFB-R593 to effectively eliminate exogenously-administered RhD-positive red blood cells from the circulation of an RhD-negative individual, thereby preventing RhD-alloimmunisation.

Start Date01 Aug 2009

Sponsor / Collaborator

Laboratoire Français du Fractionnement et des Biotechnologies

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100 Clinical Results associated with Roledumab

100 Translational Medicine associated with Roledumab

100 Patents (Medical) associated with Roledumab

Literatures (Medical) associated with Roledumab

15 Dec 2023·Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery

[Research on Runx2 gene induced differentiation of human amniotic mesenchymal stem cells into ligament fibroblasts in vitro and promotion of tendon-bone healing in rabbits].

Article

Author: Zhong, Hehe ; Xie, Tao ; Chen, Fang ; Wu, Shuhong ; Jin, Ying ; Xiang, Kuan ; Liu, Xiuqi

ObjectiveTo investigate whether the Runx2 gene can induce the differentiation of human amniotic mesenchymal stem cells (hAMSCs) to ligament fibroblasts in vitro and promote the tendon-bone healing in rabbits.MethodshAMSCs were isolated from the placentas voluntarily donated from healthy parturients and passaged, and then identified by flow cytometric identification. Adenoviral vectors carrying Runx2 gene (Ad-Runx2) and empty vector adenovirus (Ad-NC) were constructed and viral titer assay; then, the 3rd generation hAMSCs were transfected with Ad-Runx2 (Ad-Runx2 group) or Ad-NC (Ad-NC group). The real-time fluorescence quantitative PCR and Western blot were used to detect Runx2 gene and protein expression to verify the effectiveness of Ad-Runx2 transfection of hAMSCs; and at 3 and 7 days after transfection, real-time fluorescence quantitative PCR was further used to detect the expressions of ligament fibroblast-related genes [vascular endothelial growth factor (VEGF), collagen type Ⅰ, Fibronectin, and Tenascin-C]. The hAMSCs were used as a blank control group. The hAMSCs, hAMSCs transfected with Ad-NC, and hAMSCs were mixed with Matrigel according to the ratio of 1 : 1 and 1 : 2 to construct the cell-scaffold compound. Cell proliferation was detected by cell counting kit 8 (CCK-8) assay, and the corresponding cell-scaffold compound with better proliferation were taken for subsequent animal experiments. Twelve New Zealand white rabbits were randomly divided into 4 groups of sham operation group (Sham group), anterior cruciate ligament reconstruction group (ACLR group), anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-NC-scaffold compound group (Ad-NC group), and anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-Runx2-scaffold compound group (Ad-Runx2 group), with 3 rabbits in each group. After preparing the ACL reconstruction model, the Ad-NC group and the Ad-Runx2 group injected the optimal hAMSCs-Matrigel compunds into the bone channel correspondingly. The samples were taken for gross, histological (HE staining and sirius red staining), and immunofluorescence staining observation at 1 month after operation to evaluate the inflammatory cell infiltration as well as collagen and Tenascin-C content in the ligament tissues.ResultsFlow cytometric identification of the isolated cells conformed to the phenotypic characteristics of MSCs. The Runx2 gene was successfully transfected into hAMSCs. Compared with the Ad-NC group, the relative expressions of VEGF and collagen type Ⅰ genes in the Ad-Runx2 group significantly increased at 3 and 7 days after transfection ( P<0.05), Fibronectin significantly increased at 3 days ( P<0.05), and Tenascin-C significantly increased at 3 days and decreased at 7 days ( P<0.05). CCK-8 detection showed that there was no significant difference ( P>0.05) in the cell proliferation between groups and between different time points after mixed culture of two ratios. So the cell-scaffold compound constructed in the ratio of 1∶1 was selected for subsequent experiments. Animal experiments showed that at 1 month after operation, the continuity of the grafted tendon was complete in all groups; HE staining showed that the tissue repair in the Ad-Runx2 group was better and there were fewer inflammatory cells when compared with the ACLR group and the Ad-NC group; sirius red staining and immunofluorescence staining showed that the Ad-Runx2 group had more collagen typeⅠ and Ⅲ fibers, tending to form a normal ACL structure. However, the fluorescence intensity of Tenascin-C protein was weakening when compared to the ACLR and Ad-NC groups.ConclusionRunx2 gene transfection of hAMSCs induces directed differentiation to ligament fibroblasts and promotes tendon-bone healing in reconstructed anterior cruciate ligament in rabbits.

21 Sep 2023·Blood

Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression

Article

Author: Zerra, Patricia E. ; Maier, Cheryl L. ; Ayona, Diyoly ; Josephson, Cassandra D. ; Eisenbarth, Stephanie C. ; Jajosky, Ryan P. ; Chonat, Satheesh ; Hendrickson, Jeanne E. ; Arthur, Connie M. ; Wu, Shang-Chuen ; Hudson, Krystalyn E. ; Stowell, Sean R. ; Morais, Dominique ; Fasano, Ross M. ; Manis, John P. ; Patel, Kashyap R. ; Allen, Jerry William L. ; Roback, John D. ; Luckey, C. John ; Chai, Li

AbstractAntibodies against fetal red blood cell (RBC) antigens can cause hemolytic disease of the fetus and newborn (HDFN). Reductions in HDFN due to anti-RhD antibodies have been achieved through use of Rh immune globulin (RhIg), a polyclonal antibody preparation that causes antibody-mediated immunosuppression (AMIS), thereby preventing maternal immune responses against fetal RBCs. Despite the success of RhIg, it is only effective against 1 alloantigen. The lack of similar interventions that mitigate immune responses toward other RBC alloantigens reflects an incomplete understanding of AMIS mechanisms. AMIS has been previously attributed to rapid antibody-mediated RBC removal, resulting in B-cell ignorance of the RBC alloantigen. However, our data demonstrate that antibody-mediated RBC removal can enhance de novo alloimmunization. In contrast, inclusion of antibodies that possess the ability to rapidly remove the target antigen in the absence of detectable RBC clearance can convert an augmented antibody response to AMIS. These results suggest that the ability of antibodies to remove target antigens from the RBC surface can trigger AMIS in situations in which enhanced immunity may otherwise occur. In doing so, these results hold promise in identifying key antibody characteristics that can drive AMIS, thereby facilitating the design of AMIS approaches toward other RBC antigens to eliminate all forms of HDFN.

29 Aug 2023·Journal of Alzheimer's Disease

Neuropathologic Changes of Alzheimer’s Disease and Related Dementias: Relevance to Future Prevention

Article

Author: Edland, Steve E. ; Cholerton, Brenna A. ; Flanagan, Margaret E. ; White, Lon R. ; Kawas, Claudia H. ; Corrada, Maria M. ; Montine, Thomas J.

Background: Decedents with late-life dementia are often found at autopsy to have vascular pathology, cortical Lewy bodies, hippocampal sclerosis, and/or TDP-43 encephalopathy alone or with concurrent Alzheimer’s disease (AD) lesions. Nonetheless, it is commonly believed that AD neuropathologic changes (NC) are the dominant or exclusive drivers of late-life dementia. Objective: Assess associations of end-of-life cognitive impairment with any one or any combination of five distinct NC. Assess impairment prevalence among subjects having natural resistance to each type of NC. Methods: Brains from 1,040 autopsied participants of the Honolulu-Asia Study, the Nun Study, and the 90 + Study were examined for NC of AD, Lewy body dementia, microvascular brain injury, hippocampal sclerosis, and limbic predominate TDP-43 encephalopathy. Associations with impairment were assessed for each NC and for NC polymorbidity (variable combinations of 2-5 concurrent NC). Results: Among 387 autopsied decedents with severe cognitive impairment, 20.4% had only AD lesions (ADNC), 25.3% had ADNC plus 1 other NC, 11.1% had ADNC plus 2 or more other NC, 28.7% had no ADNC but 1-4 other NC, and 14.5% had no/negligible NC. Combinations of any two, three, or four NC were highly frequent among the impaired. Natural resistance to ADNC or any other single NC had a modest impact on overall cohort impairment levels. Conclusion: Polymorbidity involving 1-5 types of concurrent NC is a dominant neuropathologic feature of AD and related dementias. This represents a daunting challenge to future prevention and could explain failures of prior preventive intervention trials and of efforts to identify risk factors.

100 Deals associated with Roledumab

External Link

KEGG	Wiki	ATC	Drug Bank
-	Roledumab	-	DB16317

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Erythroblastosis, Fetal	Phase 3	-	LFB Biotechnologies SASU	-
Anemia, Hemolytic	Discovery	FR	Laboratoire Français du Fractionnement et des Biotechnologies	01 Apr 2014
Rh-Null, Regulator Type	Discovery	FR	Laboratoire Français du Fractionnement et des Biotechnologies	01 Apr 2014
Rheumatic Heart Disease	Discovery	FR	Laboratoire Français du Fractionnement et des Biotechnologies	01 Apr 2014

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02287896 (CTgov)	Phase 2	Rheumatic Heart Disease \| Rh-Null, Regulator Type	62	Roledumab (Population PK (PKS1))	hcgxjzdqbi(raqrpwvrhu) = emfigmccyg mnzzhksnmv (pbpkzrhjga, kkizfnhpkv - kcbtzdhlgg) View more	-	16 Aug 2019
				Roledumab (IM Arm Roledumab)	(ssdgkrjkip) = qpyarchpka wmkhgefpci (phiilodgha, ksidroiobc - gqfpqttbqu) View more

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