A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TST002 Intervenous Injection in Postmenopausal Women and Men With Reduced Bone Mineral Density

This is a placebo-controlled, single-ascending dose, multicenter Phase I clinical study to evaluate the safety, tolerability, PK and PD characteristics of a single intravenous infusion of TST002 in subjects with reduced bone mineral density.

Start Date28 Apr 2022

Sponsor / Collaborator

Hangzhou Just Biotherapeutics Co. Ltd.Startup

CTR20213044 / Active, not recruitingPhase 1

评估TST002注射液在骨密度降低受试者的安全性和耐受性及药代动力学的Ⅰ期临床研究

[Translation] A Phase I clinical study to evaluate the safety, tolerability and pharmacokinetics of TST002 injection in subjects with reduced bone density

主要目的：评价TST002注射液的安全性和耐受性。次要目的：描述TST002注射液的药代动力学特征；评估TST002注射液的药效学特征；评价TST002注射液的免疫原性，评价其对PK和PD的可能影响；评价TST002的群体药代动力学，并评估TST002暴露量与药效学终点之间的关系。

[Translation]

Primary objective: To evaluate the safety and tolerability of TST002 injection. Secondary objectives: To describe the pharmacokinetic characteristics of TST002 injection; To evaluate the pharmacodynamic characteristics of TST002 injection; To evaluate the immunogenicity of TST002 injection and its possible effects on PK and PD; To evaluate the population pharmacokinetics of TST002 and to evaluate the relationship between TST002 exposure and pharmacodynamic endpoints.

Start Date22 Apr 2022

Sponsor / Collaborator

Hangzhou Just Biotherapeutics Co. Ltd.Startup

NCT02337387 / TerminatedPhase 1

A Multiple-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of 2 Formulations of Blosozumab in Postmenopausal Women

The purpose of this study is to evaluate the tolerability of two different formulations of blosozumab in women who have reached menopause.
This study will last approximately 12 weeks for each participant, not including screening. Screening is required within 28 days prior to starting the study.

Start Date01 Jan 2015

Sponsor / Collaborator

Eli Lilly & Co.

100 Clinical Results associated with Blosozumab

100 Translational Medicine associated with Blosozumab

100 Patents (Medical) associated with Blosozumab

Literatures (Medical) associated with Blosozumab

31 Dec 2023·mAbs

Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4 ⁺ T cell interleukin-2 secretion

Article

Author: Mishima, Masayuki ; Ikuno, Tatsuya ; Mizuno, Hideaki ; Takeiri, Akira ; Yano, Mariko ; Arata, Yoshiyuki ; Motoyama, Shigeki ; Nishito, Yukari ; Yabuki, Nami ; Tabo, Mitsuyasu ; Matsushita, Tomochika ; Kiyokawa, Jumpei ; Suzuki, Hiromi ; Ito, Shunsuke ; Chiba, Shuichi ; Honda, Masaki ; Kubo, Chiyomi ; Sampei, Zenjiro

Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an in vitro peripheral blood mononuclear cell-based assay that can be used to assess immunogenicity potential within 3 days. This method involves examining the frequency and function of interleukin (IL)-2-secreting CD4⁺ T cells induced by therapeutic antibodies. IL-2-secreting CD4⁺ T cells seem to be functionally relevant to the immunogenic potential due to their proliferative activity and the expression of several cytokines. The rates of the donors responding to low and high immunogenic proteins, mAb1, and keyhole limpet hemocyanin were 1.3% and 93.5%, respectively. Seven antibodies with known rates of immunogenicity (etanercept, emicizumab, abciximab, romosozumab, blosozumab, humanized anti-human A33 antibody, and bococizumab) induced responses in 1.9%, 3.8%, 6.4%, 10.0%, 29.2%, 43.8%, and 89.5% of donors, respectively. These data are comparable with ADA incidences in clinical settings. Our results show that this assay can contribute to the swift assessment and mechanistic understanding of the immunogenicity of therapeutic antibodies.

01 Oct 2022·Annals of palliative medicine

Blosozumab in the treatment of postmenopausal women with osteoporosis: a systematic review and meta-analysis

Review

Author: Cai, Yuli ; Su, Yanlin ; Li, Hao ; Li, Nianhu ; Ma, Liang ; Liu, Fei ; Li, Gang ; Wang, Wenzhao

BACKGROUND:

Postmenopausal women are one of the most vulnerable groups to osteoporosis. Romosozumab is a newly monoclonal drug that inhibits the activity of sclerostin. Since it has been on the market for only 3 years, there is a lack of systematic analysis on postmenopausal women and the efficacy is not clear. In this study, we compared randomized controlled trials to assess the effects of blosozumab versus placebo in perimenopausal and postmenopausal women.

METHODS:

This meta-analysis has been registered in the PROSPERO registry (number CRD42020145839). The PubMed, Cochrane Library, ClinicalKey, and Embase databases were searched from inception date to July 01, 2021. We used the keywords "osteoporosis", "decreased bone mass", and "blosozumab" to retrieve studies on the relationship between blosozumab and osteoporosis in each database. The inclusion criteria were: (I) randomized controlled trials (RCTs) comparing the treatment of osteoporosis with blosozumab and a placebo or without treatment, (II) studies on postmenopausal women aged over 50 years, and (III) studies providing bone mineral density data. The quality of all randomized controlled trials included in this study was independently assessed by two researchers according to the Cochrane risk manual and was divided into high, medium and low quality. The main results analyzed were bone mineral density (BMD) and T-score. Our results mainly include BMD and procollagen type I N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP), and osteocalcin (OC).

RESULTS:

Three RCTs with 105 patients were selected from 157 retrieved articles. Due to high heterogeneity [BMD: Tau2=2.79; Chi2=11.70, degrees of freedom (df) =1 (P=0.0006); I2=91%], we could not perform statistical analysis of BMD. The results of BMD were then evaluated systematically. Three RCT studies were included in the evaluation. Compared with that of the placebo, blosozumab increased levels of the BMD biomarker osteocalcin [mean deviation (MD) 12.55; 95% confidence interval (CI), 8.18, 16.91; P<0.00001]. None of the 3 RCTs presented a risk of bias during the meta-analysis.

CONCLUSIONS:

The results suggested that blosozumab could be used as a target drug to improve BMD in postmenopausal women. This will provide a reference for the clinical treatment of postmenopausal women with osteoporosis.

01 Jul 2022·Journal of clinical densitometry : the official journal of the International Society for Clinical DensitometryQ4 · MEDICINE

Efficacy and safety of anti-sclerostin antibodies in the treatment of osteoporosis: A meta-analysis and systematic review

Q4 · MEDICINE

Review

Author: Raikos, Nikolaos ; Kouvelas, Dimitrios ; Poutoglidou, Frideriki ; Samoladas, Efthimios

Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of antis-sclerostin antibodies compared to placebo and conventional therapies (alendronate and teriparatide) in the treatment of osteoporosis. Randomized controlled trials were searched from PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) from their inception up to June 2021 by using Medical Subject Headings terms "anti-sclerostin antibody", "romosozumab", "blosozumab", "AMG 785″, "LY2541546", and "osteoporosis". Two investigators independently screened eligible studies, assessed the risk of bias and extracted the data from each study. The I² index was used to assess heterogeneity. Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). The GRADE approach was used to rate the quality of evidence for all the pooled outcomes. 8 RCTs with 12,416 patients met the inclusion criteria. Anti-sclerostin antibodies significantly increased lumbar spine, total hip and femoral neck bone mineral density compared to placebo, alendronate and teriparatide at both 6 and 12 mo. Adverse events were comparable between anti-sclerostin antibodies and other treatments, except for the incidence of injection-site reactions that was higher in the anti-sclerostin antibody groups. Anti-sclerostin antibodies represent a valid theurapeutic option in the treatment of osteoporosis. Further studies with longer duration and follow-up are needed to confirm the results of this meta-analysis.

News (Medical) associated with Blosozumab

31 Jul 2023

·www.prnewswire.com

Transcenta Anti-sclerostin Monoclonal Antibody TST002 (Blosozumab) Received Approval from China CDE to Initiate Phase II Clinical Trial in Patients with Reduced Bone Mineral Density

SUZHOU, China, July 30, 2023 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announces that it has received approval from China Center for Drug Evaluation (CDE) to initiate Phase II clinical trial of TST002(Blosozumab). This study aims to evaluate the safety, tolerability, and pharmacokinetics of TST002(Blosozumab) after single and multiple intravenous administrations in patients with reduced bone mineral density. Osteoporosis is a significant health concern for the middle-aged and elderly population in China. It is estimated that by 2050, the number of osteoporosis patients will reach 120 million. Compared with RANKL mAbs, sclerostin mAbs successfully achieve the dual goal of preventing bone loss and rebuilding the bone. Evenity (Romosozumab) of Amgen is the only anti-sclerostin antibody drug that has been approved by the FDA in the United States. Up to the present, there was no anti-sclerostin antibody drug approved in China. In May 2023, Transcenta presented Phase I unblinded data, which showed that the overall safety and tolerability of TST002 (Blosozumab) in all dose cohorts is favorable. On the efficacy side, all dose cohorts from 200-1,200 mg have shown a clinically meaningful increase in lumbar spine BMD on Day 85 (D85) after a single dose of TST002 (Blosozumab) and comparable to those of Blosozumab single dose study at the similar dose levels. The average increase of lumbar spine BMD at Day 85 (D85) from baseline ranged from 3.52% to 6.20% across dose cohorts, all exceeding the least significant difference (2.77%). The increase of lumbar spine BMD in the placebo group was only 0.30% even with optimal calcium and vitamin D supplemental treatment. In addition, encouraging BMD increase in total hip from 1.30% to 2.24% across dose cohorts were observed after single dose of TST002 (Blosozumab). In comparison, the mean percent change in lumbar spine BMD from baseline to month 12 was 5.4% after one year of Denosumab treatment.1 "We are excited to have received the clearance to move forward from CDE. Our Phase II will assess several regimens of TST002 (Blosozumab) with reduced dosing frequency, bringing us closer to our Phase III. We look forward to fully exploring the differentiated profile of TST002 to address the unmet medical need of the large patient population who suffers from osteoporosis," said Dr. Caroline Germa, Transcenta's Executive Vice President, Global Medicine Development and Chief Medical Officer. Reference: 1 About TST002 (Blosozumab) TST002 (Blosozumab) is a humanized anti-sclerostin monoclonal antibody as a drug candidate for osteoporosis and other bone loss diseases. It has a dual effect possessing both anabolic and anti-resorptive effects, which stimulates bone formation and inhibits bone absorption, resulting in fast increase in bone mineral density and bone strength. Blocking sclerostin activity in human treated with anti-sclerostin antibody or with naturally occurring genetic deletion has been shown to be an effective approach in increasing bone mineral density (BMD) and reducing bone fracture. Currently there is no approved anti-sclerostin antibody therapy in China yet although Romosozumab from Amgen has been approved in the United States, Europe and Japan. About Transcenta Holding Limited Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing. Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing 13 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders. For more information, please visit and . Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Transcenta, are intended to identify certain of such forward-looking statements. Transcenta does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Transcenta with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Transcenta's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Transcenta's competitive environment and political, economic, legal and social conditions. Transcenta, the Directors and the employees of Transcenta assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. SOURCE Transcenta Holding Limited

Phase 1Phase 2Clinical ResultDrug ApprovalPhase 3

17 May 2023

·www.prnewswire.com

Transcenta Announces Encouraging Phase I Clinical Data of TST002 (Blosozumab) in Chinese Patients with Reduced Bone Mineral Density

SUZHOU, China, May 16, 2023 /PRNewswire/ -- Transcenta Holding Limited ("Transcenta") (HKEX: 06628), a clinical stage biopharmaceutical company with fully-integrated capabilities in discovery, research, development and manufacturing of antibody-based therapeutics, announces encouraging phase I clinical data of TST002 (Blosozumab) in Chinese patients with reduced bone mineral density (BMD). TST002 (Blosozumab) was well tolerated and significantly increased BMD at day 85 following single intravenous injection at various doses. Transcenta in-licensed the Great China rights of Blosozumab from Eli Lilly and Company ("Eli Lilly") for development and commercialization in Greater China in 2019. Blosozumab Phase II trials in postmenopausal women in the United States and Japan have been completed by Eli Lilly. Transcenta conducted a phase I study (NCT05391776) to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of single dose of TST002 (Blosozumab) in Chinese postmenopausal women and elder men with reduced BMD. It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study with single intravenous injection of TST002 (Blosozumab) at doses of either 200, 400, 800 or 1,200 mg or matching placebo. A total of 32 patients have been enrolled and treated. Database lock and data unblinding have been completed as of May 12, 2023. Preliminary analysis of the unblinded data shows that the overall safety and tolerability of TST002 (Blosozumab) in all dose cohorts is favorable. Compared with previous clinical studies of Blosozumab in European, American and Japanese subjects, no new safety signals were found. There were no dose limiting toxicity, SAE, AE led to dose modification or death reported. All the adverse events were transient. On the efficacy side, all dose cohorts from 200-1,200 mg have shown a clinically meaningful increase in lumbar spine BMD on D85 after a single dose of TST002 (Blosozumab) and comparable to those of Blosozumab single dose study at the similar dose levels. The average increase of lumbar spine BMD at D85 from baseline ranged from 3.52% to 5.94% across dose cohorts, all exceeding the least significant difference (2.77%). The increase of lumbar spine BMD in the placebo group was only 0.3%. These results indicate that TST002 (Blosozumab) has the potential to treat osteoporosis, supporting Transcenta's plan to initiate phase II clinical studies with multiple doses once every two to three months. "We have observed encouraging preliminary BMD data with TST002 (Blosozumab) and the data generated support further exploration of our compound in a phase II. Targeting sclerostin is a well validated approach and we are confident that TST002 (Blosozumab) differentiated profile, with a reduced dosing frequency and potential for improved efficacy, will allow to address the unmet medical need of the large patient population who suffers from osteoporosis." said Dr. Caroline Germa, Transcenta's Executive Vice President, Global Medicine Development and Chief Medical Officer. About TST002 (Blosozumab) TST002 (Blosozumab) is a humanized anti-sclerostin monoclonal antibody as a drug candidate for osteoporosis and other bone loss diseases. It has a dual effect possessing both anabolic and anti-resorptive effects, which stimulates bone formation and inhibits bone absorption, resulting in fast increase in bone mineral density and bone strength. Blocking sclerostin activity in human treated with anti-sclerostin antibody or with naturally occurring genetic deletion has been shown to be an effective approach in increasing bone mineral density (BMD) and reducing bone fracture. Currently there is no approved anti-sclerostin antibody therapy in China yet although Romosozumab from Amgen has been approved in the United States, Europe and Japan. About Transcenta Holding Limited Transcenta (HKEX: 06628) is a clinical stage biopharmaceutical company with fully integrated capabilities in antibody-based biotherapeutics discovery, research, development and manufacturing. Transcenta has established global footprint, with Headquarters and Discovery, Clinical and Translational Research Center in Suzhou, Process and Product Development Center and Manufacturing Facility in Hangzhou, and Clinical Development Centers in Princeton, US and in Beijing, Shanghai and Guangzhou of China, and External Partnering Center in Boston and Los Angeles, US. Transcenta has also initiated the construction of the Group Headquarters and the second high-end biopharmaceutical facility with ICB as its core technology in Suzhou Industrial Park. Transcenta is developing 13 therapeutic antibody molecules for oncology and selected non-oncology indications including bone and kidney disorders. For more information, please visit and . Forward-Looking Statements This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Transcenta, are intended to identify certain of such forward-looking statements. Transcenta does not intend to update these forward-looking statements regularly. These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Transcenta with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Transcenta's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Transcenta's competitive environment and political, economic, legal and social conditions. Transcenta, the Directors and the employees of Transcenta assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect. SOURCE Transcenta Holding Limited

Clinical ResultPhase 1Phase 2Drug ApprovalADC

100 Deals associated with Blosozumab

External Link

KEGG	Wiki	ATC	Drug Bank
D10094	Blosozumab	-	DB12560

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteoporosis	Phase 2	US	Eli Lilly & Co.	01 Aug 2010
Osteoporosis	Phase 2	JP	Eli Lilly & Co.	01 Aug 2010
Osteoporosis	Phase 2	DK	Eli Lilly & Co.	01 Aug 2010
Osteoporosis	Phase 2	EE	Eli Lilly & Co.	01 Aug 2010
Osteoporosis	Phase 2	LT	Eli Lilly & Co.	01 Aug 2010
Osteoporosis, Postmenopausal	Phase 1	US	Eli Lilly & Co.	01 Apr 2014

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


PRNewswire Manual	Phase 1	Osteoporosis	-	Blosozumab	cwuuatqssu(ylwuqoxwno) = The average increase of lumbar spine BMD at Day 85 (D85) from baseline ranged from 3.52% to 6.20% across dose cohorts, all exceeding the least significant difference (2.77%). The increase of lumbar spine BMD in the placebo group was only 0.30% even with optimal calcium and vitamin D supplemental treatment. cvfzrlgtxk (wkokoopcnk )	Positive	30 Jul 2023
				placebo
NCT01742078 (CTgov)	Phase 1	-	60	LY2541546 - IV (7.5 mg LY2541546 - IV)	ntwruyvldy(mrnlpsblys) = xogfogijnj rpdhjqunft (tpsitovgay, torcidcqii - jysangoipy) View more	-	23 Jan 2019
				LY2541546 - IV (25 mg LY2541546 - IV)	ntwruyvldy(mrnlpsblys) = khsivcctxp rpdhjqunft (tpsitovgay, quhpqyupeq - ahpxprwawh) View more
NCT02337387 (CTgov)	Phase 1	Osteoporosis, Postmenopausal	28	Blosozumab (Blosozumab Formulation A)	ilbixysbau(lrazbrcfit) = nykobeljfd vubamkfvvq (likeynqvtm, vwxxiojtat - zhtheubmju) View more	-	22 Jan 2019
				Blosozumab (Blosozumab Formulation B)	ilbixysbau(lrazbrcfit) = lkuywvthja vubamkfvvq (likeynqvtm, nuscnvhtmg - rhkstcafig) View more
NCT01742091 (CTgov)	Phase 1	-	59	Placebo - SC+LY2541546 - SC (180 mg LY2541546 SC Q4W)	ezsdnyzvbs(yuxdjredbt) = ntgakiknpl chznicjbcy (seavkdqfcn, hrzwbbmgws - ualejeyany) View more	-	18 Jul 2018
				LY2541546 - SC (270 mg LY2541546 SC Q2W)	ezsdnyzvbs(yuxdjredbt) = bgnknwnvtp chznicjbcy (seavkdqfcn, defgrfzfdh - ewjpqanpfx) View more
NCT02109042 (CTgov)	Phase 1	Osteoporosis, Postmenopausal	15	Blosozumab (Weekly SC Blosozumab Injections)	vgxngsmsdw(ovdauoakky) = lsfkkxsyvl yyhfjicqeg (bfschywtqw, nqzdobsjcz - recxqvbkrz) View more	-	16 Jul 2018
				Blosozumab (180 mg SC Blosozumab Injection)	zvefudlwxn(upafjplydt) = scwfnnbmbw vnqhscvikd (eurxqldflu, pljrxecnsi - fyzdugvidg) View more
NCT01144377 (CTgov)	Phase 2	Osteoporosis	154	Placebo+LY2541546 (180 mg LY2541546 Q4W + Placebo)	fxlrzqhqts(pkmjwtrhth) = shbfvswpjw iggdvckfcp (rwjcczeofe, wkbltslhbr - mfomzbytcw) View more	-	04 Dec 2017
				LY2541546 (180 mg LY2541546 Q2W)	fxlrzqhqts(pkmjwtrhth) = edfzvwwfxe iggdvckfcp (rwjcczeofe, ibhnvlwtgh - xafmojkrex) View more

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