Treatment of thrombocytopenia in connective tissue diseases with Telitacicept

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

This study is testing if a new treatment called Telitacicept can help people with low platelet counts caused by connective tissue diseases feel better.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 296 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Beijing Hospital (other gov)
• Drugs / interventions: Rituximab, Epratuzumab, Belimumab, methotrexate, cyclophosphamide, prednisone
• Locations: 23 sites (Hefei, Anhui and 22 other locations)
• Trial ID: NCT05998759 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of Telitacicept, a biological agent, for treating thrombocytopenia associated with connective tissue diseases. Participants diagnosed with conditions such as primary Sjögren syndrome, systemic lupus erythematosus, or undifferentiated connective tissue disease will be randomly assigned to receive either Telitacicept or a placebo weekly for 24 weeks. The study is designed as a randomized, double-blind, placebo-controlled trial, ensuring unbiased results while maintaining stable background therapy throughout the treatment period.

Who should consider this trial

Good fit: Ideal candidates include individuals diagnosed with connective tissue disease-associated thrombocytopenia who have not responded adequately to standard treatments.

Not a fit: Patients who do not have connective tissue diseases or those with thrombocytopenia not associated with these conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve platelet counts and overall health for patients suffering from thrombocytopenia related to connective tissue diseases.

How similar studies have performed: While this approach is relatively novel, previous studies on targeted therapies for similar conditions have shown promising results.

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

Where this trial is running

Hefei, Anhui and 22 other locations

• The First Affiliated Hospital of Anhui Medical College — Hefei, Anhui, China (RECRUITING)
• The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial) — Hefei, Anhui, China (RECRUITING)
• Beijing Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Peking University People's Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Peking University Third Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• First Affiliated Hospital, Sun Yat-Sen University — Guangzhou, Guangdong, China (RECRUITING)
• Guangdong Provincial People's Hospital — Guangzhou, Guangdong, China (RECRUITING)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (RECRUITING)
• Wuhan Union Hospital, China — Wuhan, Hubei, China (RECRUITING)
• Second Xiangya Hospital of Central South University — Changsha, Hunan, China (RECRUITING)
• Xiangya Hospital of Central South University — Changsha, Hunan, China (RECRUITING)
• The Affiliated Hospital of Inner Mongolia Medical University — Hohhot, Inner Mongolia, China (RECRUITING)
• First Hospital of China Medical University — Shenyang, Liaoning, China (RECRUITING)
• Shandong Provincial Hospital — Jinan, Shandong, China (RECRUITING)
• Changhai Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)
• RenJi Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)
• Shanxi Bethune Hospital — Taiyuan, Shanxi, China (RECRUITING)
• West China Hospital — Chengdu, Sichuan, China (RECRUITING)
• Institute of Hematology & Blood Diseases Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• Tianjin First Central Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• Tianjin Medical University General Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• People's Hospital of Xinjiang Uygur Autonomous Region — Ürümqi, Xinjiang Uygur Autonomous Region, China (RECRUITING)
• The First People's Hospital of Yunnan — Kunming, Yunnan, China (RECRUITING)

Study contacts

• Principal investigator: Shengqian Xu, MD. — The First Affiliated Hospital of Anhui Medical Hospital
• Study coordinator: Xuan Zhang, MD.

Conditions: Connective Tissue Diseases, Thrombocytopenia, biological agents, B cell, targeted therapy