Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
Study Details
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 |
|---|---|---|
|
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
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:
|
| 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:
|
Outcome Measures
Primary Outcome Measures
- Overall response (CR + PR) rate [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 [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 [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 [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 [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 [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 [at week 24]
According to the NCI CTCAE 5.0
- treatment related severe adverse event [at week 24]
According to the NCI CTCAE 5.0
- bleeding scale [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 [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 [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) [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) [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) [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 [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 [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 [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 [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 [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 [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 [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 [at week 24]
(peripheral plasmablast count at week 24-peripheral plasmablast count at baseline)/ peripheral plasmablast count at baseline.
Eligibility Criteria
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)
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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
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50×109/L>PLT ≥20×109/L
-
anti-nuclear antibody (ANA) positive (≥1:80, any karyotype) detected in the laboratory of each research center
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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.)
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Hematopoietic system disorders, such as myelodysplastic syndrome, paroxysmal sleep hemoglobinuria, aplastic anemia, leukemia, lymphoma, myelofibrosis and so on
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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)
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Arteriovenous thromboembolism events
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Receiving antiplatelet or anticoagulant therapy at screening
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Clinically significant electrocardiogram changes
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corrected Q-T interval (QTc)>450ms for male, QTc>470ms for female
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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%)]
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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
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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
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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
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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)
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Subjects with known active infections (e.g., shingles, COVID-19, HIV, active tuberculosis, etc.), and active or recurrent gastrointestinal ulcers
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Pregnant or lactating women, and subjects with a during plan during the trial
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Allergic reaction: history of allergic reactions to human biological products
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Treatment with B cell-targeting agents such as Rituximab or Epratuzumab or Belimumab six months prior to randomization
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Treatment with tumor necrosis factor (TNF) inhibitors or TNF-receptor blockers six months prior to randomization
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Participating in clinical trial 28 days or 5 drug half-lives of the investigational agents prior to randomization
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Received live vaccine 28 days prior to randomization
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Treatment with thrombopoietin receptor agonists such as Eltrombopag or Romiplostim 28 days prior to randomization
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Subjects with depression or suicidal thoughts
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Previous treatment with telitacicept
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B cell targeting drug therapy is not tolerated or responsive
-
Investigator considers candidates not appropriating for the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial) | Hefei | Anhui | China | |
| 2 | Beijing Hospital | Beijing | Beijing | China | |
| 3 | Peking University People's Hospital | Beijing | Beijing | China | |
| 4 | Peking University Third Hospital | Beijing | Beijing | China | |
| 5 | First Affiliated Hospital, Sun Yat-Sen University | Guangzhou | Guangdong | China | |
| 6 | Guangdong Provincial People's Hospital | Guangzhou | Guangdong | China | |
| 7 | The First Affiliated Hospital of Zhengzhou University | Zhengzhou | Henan | China | |
| 8 | Wuhan Union Hospital, China | Wuhan | Hubei | China | |
| 9 | Second Xiangya Hospital of Central South University | Changsha | Hunan | China | |
| 10 | Xiangya Hospital of Central South University | Changsha | Hunan | China | |
| 11 | The Affiliated Hospital of Inner Mongolia Medical University | Hohhot | Inner Mongolia Autonomous Region | China | |
| 12 | First Hospital of China Medical University | Shenyang | Liaoning | China | |
| 13 | Shandong Provincial Hospital | Jinan | Shandong | China | |
| 14 | Changhai Hospital | Shanghai | Shanghai | China | |
| 15 | RenJi Hospital | Shanghai | Shanghai | China | |
| 16 | Shanxi Bethune Hospital | Taiyuan | Shanxi | China | |
| 17 | West China Hospital | Chengdu | Sichuan | China | |
| 18 | Institute of Hematology & Blood Diseases Hospital | Tianjin | Tianjin | China | |
| 19 | Tianjin First Central Hospital | Tianjin | Tianjin | China | |
| 20 | Tianjin Medical University General Hospital | Tianjin | Tianjin | China | |
| 21 | People's Hospital of Xinjiang Uygur Autonomous Region | Ürümqi | Xinjiang Uygur Autonomous Region | China | |
| 22 | The First People's Hospital of Yunnan | Kunming | Yunnan | China |
Sponsors and Collaborators
- Beijing Hospital
- 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
- Tianjin First Central Hospital
- Tianjin Medical University General Hospital
- People's Hospital of Xinjiang Uygur Autonomous Region
- The First People's Hospital of Yunnan
Investigators
- Study Chair: Xuan Zhang, MD., Beijing Hospital
- Study Chair: Yongjing Cheng, MD., Beijing Hospital
- Principal Investigator: Zhu Chen, MD., The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial)
- Principal Investigator: Jing He, MD., Peking University People's Hospital
- Principal Investigator: Rong Mu, MD., Peking University Third Hospital
- Principal Investigator: Niansheng Yang, MD., First Affiliated Hospital, Sun Yat-Sen University
- Principal Investigator: Yang Li, MD., Guangdong Provincial People's Hospital
- Principal Investigator: Shengyun Liu, MD., The First Affiliated Hospital of Zhengzhou University
- Principal Investigator: Anbin Huang, MD., Wuhan Union Hospital, China
- Principal Investigator: Fen Li, MD., Second Xiangya Hospital of Central South University
- Principal Investigator: Hui Luo, MD., Xiangya Hospital of Central South University
- Principal Investigator: Hongbin Li, MD., The Affiliated Hospital of Inner Mongolia Medical University
- Principal Investigator: Pinting Yang, MD., First Hospital of China Medical University
- Principal Investigator: Hongsheng Sun, MD., Shandong Provincial Hospital
- Principal Investigator: Dongbao Zhao, MD., Changhai Hospital
- Principal Investigator: Sheng Chen, MD., RenJi Hospital
- Principal Investigator: Liyun Zhang, MD., Shanxi Bethune Hospital
- Principal Investigator: Qibing Xie, MD., West China Hospital
- Principal Investigator: Lei Zhang, MD., Institute of Hematology & Blood Diseases Hospital
- Principal Investigator: Wufang Qi, MD., Tianjin First Central Hospital
- Principal Investigator: Wei Wei, MD., Tianjin Medical University General Hospital
- Principal Investigator: Lijun Wu, MD., People's Hospital of Xinjiang Uygur Autonomous Region
- Principal Investigator: Qin Li, MD., The First People's Hospital of Yunnan
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BJ-2021-235
- BJ-2021-235
- RCTAIIRCTD001