Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia

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ClinicalTrials.gov Identifier: NCT05998759

Recruitment Status : Not yet recruiting

First Posted : August 21, 2023

Last Update Posted : September 21, 2023

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View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)

Peking University People's Hospital

Peking University Third Hospital

First Affiliated Hospital, Sun Yat-Sen University

Guangdong Provincial People's Hospital

The First Affiliated Hospital of Zhengzhou University

Wuhan Union Hospital, China

Second Xiangya Hospital of Central South University

Xiangya Hospital of Central South University

The Affiliated Hospital of Inner Mongolia Medical University

First Hospital of China Medical University

Shandong Provincial Hospital

Changhai Hospital

RenJi Hospital

Shanxi Bethune Hospital

West China Hospital

Institute of Hematology & Blood Diseases Hospital, China

Tianjin First Central Hospital

Tianjin Medical University General Hospital

People's Hospital of Xinjiang Uygur Autonomous Region

The First People's Hospital of Yunnan

Information provided by (Responsible Party):

Yongjing Cheng, Beijing Hospital

Study Description

Brief Summary:

The goal of this clinical trial is to evaluate the efficacy and safety of Telitacicept for the treatment of connective tissue disease-associated thrombocytopenia.

Condition or disease	Intervention/treatment	Phase
Connective Tissue Diseases Thrombocytopenia	Biological: Telitacicept Drug: Placebo	Phase 2

Detailed Description:

In this randomized, double-blind placebo-controlled study, the investigators aim to evaluate the efficacy and safety of Telitacicept for the treatment of connective tissue disease-associated thrombocytopenia. After screening, eligible participants will be randomized at a 1: 1 ratio to receive either subcutaneous Telitacicept 160 mg or placebo once a week for 24 weeks. The background standard therapy is maintained stable during the whole treatment period.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	296 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-blind Placebo-controlled Study of Recombinant Human B Lymphocyte Stimulating Factor Receptor-Fc Fusion Protein for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
Estimated Study Start Date :	October 2023
Estimated Primary Completion Date :	December 2025
Estimated Study Completion Date :	December 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Connective Tissue Disorders

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Telitacicept plus standard therapy Telitacicept (160mg ih qw for 24 weeks) combined with standard therapy. Standard therapy refers to the following treatment (monotherapy or in combination): glucocorticoid, hydroxychloroquine, and other immunosuppressants (i.e. cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, methotrexate and leflunomide, et al.).	Biological: Telitacicept subcutaneous telitacicept 160 mg weekly for 24 weeks. Other Names: recombinant human B lymphocyte stimulating factor receptor-Fc fusion protein Recombinant Human B Lymphocyte(RC18) Tai'ai®
Placebo Comparator: Placebo plus standard therapy Placebo combined with standard therapy. Standard therapy refers to the following treatment (monotherapy or in combination): glucocorticoid, hydroxychloroquine, and other immunosuppressants (i.e. cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, methotrexate and leflunomide, et al.).	Drug: Placebo subcutaneous placebo weekly for 24 weeks. Other Names: Placebo control control

Outcome Measures

Primary Outcome Measures :

Overall response (CR + PR) rate [ Time Frame: at week 24 ]
Response is deemed as complete (CR) if the platelet (PLT) count is ≥ 100×10^9/L, partial (PR) if the platelet count ranges from 50×10^9/L to 100×10^9/L and at least doubled from baseline. No active bleeding is allowed in participants classified as CR or PR.

Secondary Outcome Measures :

Overall response (CR + PR) rate [ Time Frame: at week 12 ]
Response is deemed as complete (CR) if the platelet count is ≥ 100×10^9/L, partial (PR) if the platelet count ranges from 50×10^9/L to 100×10^9/L and at least doubled from baseline. No active bleeding is allowed in participants classified as CR or PR.
Rescue treatment rate [ Time Frame: at week 24 ]
Rescue treatment is initiated if the platelet count is <10×10^9/L, or the participant is with active bleeding, or based on the investigator's judgement when the platelet count ranges from 10×10^9/L to 20×10^9/L.
Time to rescue treatment [ Time Frame: at week 24 ]
Time to rescue treatment refers to period duration from the initiation of Telitacicept or placebo (day 1) to rescue treatment.
Relapse rate [ Time Frame: at week 24 ]
No response refers to the platelet count is < 50×10^9/L, or increases for less than 1-fold from baseline, or with active central nervous system or digestive tract bleeding, or rescue treatment is initiated. Relapse is defined as no response recurring after a complete or partial response lasting for at least 7 days with treatment.
Time to relapse [ Time Frame: at week 24 ]
Time to relapse refers to period duration from the initiation of Telitacicept or placebo (day 1) to relapse.
treatment related adverse event [ Time Frame: at week 24 ]
According to the NCI CTCAE 5.0
treatment related severe adverse event [ Time Frame: at week 24 ]
According to the NCI CTCAE 5.0
bleeding scale [ Time Frame: at week 24 ]
According to the ITP bleeding scale (IBLS). The IBLS comprises of 11 grades from 0 (none) to 2 (marked bleeding) by history over the previous week or by exam; 2 being worse. These 11 grades include: skin by physical exam, oral by physical exam, skin by history, oral by history, epistaxis, gastrointestinal, urinary, gynecological, pulmonary, intracranial hemorrhage, and subconjunctival hemorrhage.

Other Outcome Measures:

life quality 1 [ Time Frame: at week 24 ]
According to the ITP Patient Assessment Questionnaire™ (ITP-PAQ™) score. The ITP-PAQ™ is a disease-specific instrument that was designed to measure the Quality of Life (QoL) of adult patients with immune thrombocytopenia. The items employ a 4-week recall with responses recorded on 4-, 5- or 7-point Likert scales. All item scores are transformed to a 0 to 100 continuum where higher scores represent better QoL and are weighted equally to derive the scale scores.
life quality 2 [ Time Frame: at week 24 ]
According to the FACT-Th6 score. The Functional Assessment of Cancer Therapy-Thrombocytopenia (FACT-Th6) consists of 6 questions in which patients rate (0-4) their general degree of worry related to bleeding and bruising, and resulting activity impairment and frustration. Items were reverse-scored as necessary such that higher scores represent higher Health-related quality of life (HRQoL). Total scores ranged from 0 to 24. Recall period is previous 7 days.
Absolute change rate from baseline in serum immunoglobulin G (IgG) [ Time Frame: at week 24 ]
(serum IgG level at week 24-serum IgG level at baseline)/ serum IgG level at baseline
Absolute change rate from baseline in serum immunoglobulin M (IgM) [ Time Frame: at week 24 ]
(serum IgM level at week 24-serum IgM level at baseline)/ serum IgM level at baseline
Absolute change rate from baseline in serum immunoglobulin A (IgA) [ Time Frame: at week 24 ]
(serum IgA level at week 24-serum IgA level at baseline)/ serum IgA level at baseline
Absolute change rate from baseline in serum C3 [ Time Frame: at week 24 ]
(serum C3 level at week 24-serum C3 level at baseline)/ serum C3 level at baseline
Absolute change rate from baseline in serum C4 [ Time Frame: at week 24 ]
(serum C4 level at week 24-serum C4 level at baseline)/ serum C4 level at baseline
Absolute change rate from baseline in serum anti-platelet antibody [ Time Frame: at week 24 ]
(serum anti-platelet antibody level at week 24-serum anti-platelet antibody level at baseline)/ serum anti-platelet antibody level at baseline
Absolute change rate from baseline in serum Blys [ Time Frame: at week 24 ]
(serum Blys level at week 24-serum Blys level at baseline)/ serum Blys level at baseline. Blys is short for B lymphocyte stimulator.
Absolute change rate from baseline in serum APRIL [ Time Frame: at week 24 ]
(serum APRIL level at week 24-serum APRIL level at baseline)/ serum APRIL level at baseline. APRIL is short for a proliferation-inducing ligand.
Absolute change rate from baseline in peripheral naive B cell count [ Time Frame: at week 24 ]
(peripheral naive B cell count at week 24-peripheral naive B cell count at baseline)/ peripheral naive B cell count at baseline.
Absolute change rate from baseline in peripheral plasma cell count [ Time Frame: at week 24 ]
(peripheral plasma cell count at week 24-peripheral plasma cell count at baseline)/ peripheral plasma cell count at baseline.
Absolute change rate from baseline in peripheral plasmablast count [ Time Frame: at week 24 ]
(peripheral plasmablast count at week 24-peripheral plasmablast count at baseline)/ peripheral plasmablast count at baseline.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subjects who have been diagnosed with connective tissue disease (CTD)-associated thrombocytopenia. And CTD includes primary Sjögren syndrome (according to the 2002 American College of Rheumatology (ACR)/ European League against Rheumatism (EULAR) classification criteria), systemic lupus erythematosus (SLE, according to the 1997 or the 2009 ACR classification criteria), and undifferentiated connective tissue disease (according to the 1999 international classification criteria)
Refractory thrombocytopenia defined as:

Either: Failure to maintain sustained remission after treatment by oral glucocorticoid dose ≥1 mg/kg/day for at least 4 weeks (prednisone or equivalent) and at least one immunosuppressant (i.e. cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, methotrexate, leflunomide and hydroxychloroquine, et al.) Or: Relapse during oral glucocorticoid tapering or after withdrawal

50×10^9/L>PLT ≥20×10^9/L
anti-nuclear antibody (ANA) positive (≥1:80, any karyotype) detected in the laboratory of each research center
Standard therapy should be maintained stable for at least 28 days prior to the first dose of the experimental drug or placebo. Standard therapy refers to the following treatment (monotherapy or in combination): glucocorticoid, hydroxychloroquine, and other immunosuppressants (i.e. cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, methotrexate and leflunomide, et al.)
Signed informed consent form, willing or able to participate in all required study evaluations and procedures

Exclusion Criteria:

Vital organ lethal bleeding (including but not limited to central nervous system bleeding, digestive tract bleeding) at screening, or intracranial bleeding 6 months prior to screening
Antiphospholipid syndrome, thrombotic thrombocytopenia purpura, hemolytic uremic syndrome, or thrombocytopenia secondary to other causes (such as sepsis, Epstein-Barr virus infection, cytomegalovirus infection, Corona Virus Disease-19 (COVID-19) infection, drugs, etc.)
Hematopoietic system disorders, such as myelodysplastic syndrome, paroxysmal sleep hemoglobinuria, aplastic anemia, leukemia, lymphoma, myelofibrosis and so on
Severe cardiovascular system disease, including: unstable or uncontrollable disease or condition affecting the function of the heart (such as angina pectoris, congestive heart failure, uncontrolled hypertension or arrhythmia)
Arteriovenous thromboembolism events
Receiving antiplatelet or anticoagulant therapy at screening
Clinically significant electrocardiogram changes
corrected Q-T interval (QTc)>450ms for male, QTc>470ms for female
Severe pulmonary disease, including: unstable or uncontrollable disease or condition affecting respiratory function [e.g., diffuse alveolar hemorrhage, severe pulmonary hypertension, severe pulmonary interstitial disease (peripheral blood oxygen saturation <92% at rest without oxygen, or forced vital capacity (FVC)<50%, or carbon monoxide diffusing capacity (DLCO)<50%)]
Severe kidney disease, including: severe lupus nephritis (urinary protein > 6 g/24 hours or endogenous creatinine clearance < 30 ml /min) 8 weeks prior to randomization, active nephritis requiring current protocol disallowed drugs, severe renal insufficiency requiring hemodialysis or prednisone ≥100mg/ day (or equivalent) for ≥14 days
SLE or non-SLE related central nervous system disease (including epilepsy, psychosis, organic encephalopathy syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis) 8 weeks prior to randomization
Active hepatitis, a history of severe liver disease. Subjects positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus are excluded. As for subjects with antibodies to hepatitis B core antigen (HBcAb), further hepatitis B virus (HBV)-DNA should be tested. If HBV-DNA is negative, subjects could be enrolled; otherwise, subjects should be excluded
Abnormal laboratory results (including but not limited to: alanine aminotransferase (ALT) or aspertate aminotransferase (AST)≥3×ULN (upper limit of normal), white blood cell count <1.5×10^9/L)
Subjects with known active infections (e.g., shingles, COVID-19, HIV, active tuberculosis, etc.), and active or recurrent gastrointestinal ulcers
Pregnant or lactating women, and subjects with a during plan during the trial
Allergic reaction: history of allergic reactions to human biological products
Treatment with B cell-targeting agents such as Rituximab or Epratuzumab or Belimumab six months prior to randomization
Treatment with tumor necrosis factor (TNF) inhibitors or TNF-receptor blockers six months prior to randomization
Participating in clinical trial 28 days or 5 drug half-lives of the investigational agents prior to randomization
Received live vaccine 28 days prior to randomization
Treatment with thrombopoietin receptor agonists such as Eltrombopag or Romiplostim 28 days prior to randomization
Subjects with depression or suicidal thoughts
Previous treatment with telitacicept
B cell targeting drug therapy is not tolerated or responsive
Investigator considers candidates not appropriating for the study

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05998759

Contacts

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Contact: Xuan Zhang, MD.	+86-01085136736	zxpumch2003@sina.com
Contact: Yongjing Cheng, MD.	+86-01085136736	chengyongjing3427@njhmoh.cn

Locations

Show 22 study locations

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China, Anhui
The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)
Hefei, Anhui, China
Contact: Zhu Chen, MD.
China, Beijing
Beijing Hospital
Beijing, Beijing, China
Contact: Xuan Zhang, MD.
Contact: Yongjing Cheng, MD.
Sub-Investigator: Like Zhao, MD.
Sub-Investigator: Zhe Chen, MD.
Sub-Investigator: Ru Feng, MD.
Sub-Investigator: Fang Wang, MD.
Sub-Investigator: Yingjuan Chen, MD.
Sub-Investigator: Min Wang, MD.
Sub-Investigator: Qian Wang, MD.
Sub-Investigator: Min Feng, MD.
Sub-Investigator: Yanxiang Luo, MD.
Peking University People's Hospital
Beijing, Beijing, China
Contact: Jing He, MD.
Peking University Third Hospital
Beijing, Beijing, China
Contact: Rong Mu
China, Guangdong
First Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, China
Contact: Niansheng Yang, MD.
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Contact: Yang Li, MD.
China, Henan
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
Contact: Shengyun Liu, MD.
China, Hubei
Wuhan Union Hospital, China
Wuhan, Hubei, China
Contact: Anbin Huang, MD.
China, Hunan
Second Xiangya Hospital of Central South University
Changsha, Hunan, China
Contact: Fen Li, MD.
Xiangya Hospital of Central South University
Changsha, Hunan, China
Contact: Hui Luo, MD.
China, Inner Mongolia Autonomous Region
The Affiliated Hospital of Inner Mongolia Medical University
Hohhot, Inner Mongolia Autonomous Region, China
Contact: Hongbin Li, MD.
China, Liaoning
First Hospital of China Medical University
Shenyang, Liaoning, China
Contact: Pinting Yang, MD.
China, Shandong
Shandong Provincial Hospital
Jinan, Shandong, China
Contact: Hongsheng Sun, MD.
China, Shanghai
Changhai Hospital
Shanghai, Shanghai, China
Contact: Dongbao Zhao, MD.
RenJi Hospital
Shanghai, Shanghai, China
Contact: Sheng Chen, MD.
China, Shanxi
Shanxi Bethune Hospital
Taiyuan, Shanxi, China
Contact: Liyun Zhang, MD.
China, Sichuan
West China Hospital
Chengdu, Sichuan, China
Contact: Qibing Xie, MD.
China, Tianjin
Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin, China
Contact: Lei Zhang, MD.
Tianjin First Central Hospital
Tianjin, Tianjin, China
Contact: Wufang Qi, MD.
Tianjin Medical University General Hospital
Tianjin, Tianjin, China
Contact: Wei Wei, MD.
China, Xinjiang Uygur Autonomous Region
People's Hospital of Xinjiang Uygur Autonomous Region
Ürümqi, Xinjiang Uygur Autonomous Region, China
Contact: Lijun Wu, MD.
China, Yunnan
The First People's Hospital of Yunnan
Kunming, Yunnan, China
Contact: Qin Li, MD.

Sponsors and Collaborators

Beijing Hospital