Clinical trial NCT05998759: Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Connective Tissue Diseases
Thrombocytopenia
Keywords: Connective Tissue Diseases
Thrombocytopenia
biological agents
B cell
targeted therapy
Lead sponsor: Beijing Hospital
Sponsor class: OTHER_GOV
Collaborators: name: The First Affiliated Hospital of Anhui Medical University
name: The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)
name: Peking University People's Hospital
name: Peking University Third Hospital
name: First Affiliated Hospital, Sun Yat-Sen University
name: Guangdong Provincial People's Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: Wuhan Union Hospital, China
name: Second Xiangya Hospital of Central South University
name: Xiangya Hospital of Central South University
name: The Affiliated Hospital of Inner Mongolia Medical University
name: First Hospital of China Medical University
name: Shandong Provincial Hospital
name: Changhai Hospital
name: RenJi Hospital
name: Shanxi Bethune Hospital
name: West China Hospital
name: Institute of Hematology & Blood Diseases Hospital, China
name: Tianjin First Central Hospital
name: Tianjin Medical University General Hospital
name: People's Hospital of Xinjiang Uygur Autonomous Region
name: The First People's Hospital of Yunnan
First posted: 2023-08-21
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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 glucocorticoid 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
* 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 14 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 unstable dosage of thrombopoietin receptor agonists such as Eltrombopag or Romiplostim 14 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

Primary outcomes:
measure: Overall response (CR + PR) rate
timeFrame: at week 24
Secondary outcomes:
measure: Overall response (CR + PR) rate
timeFrame: at week 12
measure: Rescue treatment rate
timeFrame: at week 24
measure: Time to rescue treatment
timeFrame: at week 24
measure: Relapse rate
timeFrame: at week 24
measure: Time to relapse
timeFrame: at week 24
measure: treatment related adverse event
timeFrame: at week 24
measure: treatment related severe adverse event
timeFrame: at week 24
measure: bleeding scale
timeFrame: at week 24
Other outcomes:
measure: life quality 1
timeFrame: at week 24
measure: life quality 2
timeFrame: at week 24
measure: Absolute change rate from baseline in serum immunoglobulin G (IgG)
timeFrame: at week 24
measure: Absolute change rate from baseline in serum immunoglobulin M (IgM)
timeFrame: at week 24
measure: Absolute change rate from baseline in serum immunoglobulin A (IgA)
timeFrame: at week 24
measure: Absolute change rate from baseline in serum C3
timeFrame: at week 24
measure: Absolute change rate from baseline in serum C4
timeFrame: at week 24
measure: Absolute change rate from baseline in serum anti-platelet antibody
timeFrame: at week 24
measure: Absolute change rate from baseline in serum Blys
timeFrame: at week 24
measure: Absolute change rate from baseline in serum APRIL
timeFrame: at week 24
measure: Absolute change rate from baseline in peripheral naive B cell count
timeFrame: at week 24
measure: Absolute change rate from baseline in peripheral plasma cell count
timeFrame: at week 24
measure: Absolute change rate from baseline in peripheral plasmablast count
timeFrame: at week 24
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Guangzhou
country: China
facility: First Affiliated Hospital, Sun Yat-Sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Wuhan Union Hospital, China
state: Hubei
city: Changsha
country: China
facility: Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia Autonomous Region
city: Shenyang
country: China
facility: First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Provincial Hospital
state: Shandong
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: RenJi Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin First Central Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Ürümqi
country: China
facility: People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang Uygur Autonomous Region
city: Kunming
country: China
facility: The First People's Hospital of Yunnan
state: Yunnan
Study officials:
affiliation: Beijing Hospital
name: Xuan Zhang, MD.
role: STUDY_CHAIR
affiliation: Beijing Hospital
name: Yongjing Cheng, MD.
role: STUDY_CHAIR
affiliation: The First Affiliated Hospital of Anhui Medical Hospital
name: Shengqian Xu, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)
name: Zhu Chen, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University People's Hospital
name: Jing He, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Peking University Third Hospital
name: Rong Mu, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Niansheng Yang, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Guangdong Provincial People's Hospital
name: Yang Li, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: The First Affiliated Hospital of Zhengzhou University
name: Guanmin Gao, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuhan Union Hospital, China
name: Anbin Huang, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Xiangya Hospital of Central South University
name: Fen Li, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Xiangya Hospital of Central South University
name: Hui Luo, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: The Affiliated Hospital of Inner Mongolia Medical University
name: Hongbin Li, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: First Hospital of China Medical University
name: Pinting Yang, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shandong Provincial Hospital
name: Hongsheng Sun, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Changhai Hospital
name: Dongbao Zhao, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: RenJi Hospital
name: Sheng Chen, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Shanxi Bethune Hospital
name: Liyun Zhang, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: West China Hospital
name: Qibing Xie, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin First Central Hospital
name: Wufang Qi, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tianjin Medical University General Hospital
name: Wei Wei, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: People's Hospital of Xinjiang Uygur Autonomous Region
name: Lijun Wu, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Yunnan
name: Qin Li, MD.
role: PRINCIPAL_INVESTIGATOR
References: