Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia

Thrombocytopenia Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05998759
• Other study ID #: BJ-2021-235
• Secondary ID: BJ-2021-235RCTAI
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 2023
• Est. completion date: December 2025

Study information

• Verified date: September 2023
• Source: Beijing Hospital
• Contact: Xuan Zhang, MD.
• Phone: +86-01085136736
• Email: zxpumch2003[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 296
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Connective Tissue Diseases
• Thrombocytopenia

Intervention

Biological:
• Telitacicept
subcutaneous telitacicept 160 mg weekly for 24 weeks.

Drug:
• Placebo
subcutaneous placebo weekly for 24 weeks.

Locations

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

Sponsors (22)

Lead Sponsor

Collaborator

Beijing Hospital

Changhai Hospital, First Affiliated Hospital, Sun Yat-Sen University, First Hospital of China Medical University, Guangdong Provincial People's Hospital, Institute of Hematology & Blood Diseases Hospital, China, Peking University People's Hospital, Peking University Third Hospital, People's Hospital of Xinjiang Uygur Autonomous Region, RenJi Hospital, Second Xiangya Hospital of Central South University, Shandong Provincial Hospital, Shanxi Bethune Hospital, The Affiliated Hospital of Inner Mongolia Medical University, The First Affiliated Hospital of China University of Science and Technology (Anhui Provincial), The First Affiliated Hospital of Zhengzhou University, The First People's Hospital of Yunnan, Tianjin First Central Hospital, Tianjin Medical University General Hospital, West China Hospital, Wuhan Union Hospital, China, Xiangya Hospital of Central South University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	life quality 1	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.	at week 24
Other	life quality 2	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.	at week 24
Other	Absolute change rate from baseline in serum immunoglobulin G (IgG)	(serum IgG level at week 24-serum IgG level at baseline)/ serum IgG level at baseline	at week 24
Other	Absolute change rate from baseline in serum immunoglobulin M (IgM)	(serum IgM level at week 24-serum IgM level at baseline)/ serum IgM level at baseline	at week 24
Other	Absolute change rate from baseline in serum immunoglobulin A (IgA)	(serum IgA level at week 24-serum IgA level at baseline)/ serum IgA level at baseline	at week 24
Other	Absolute change rate from baseline in serum C3	(serum C3 level at week 24-serum C3 level at baseline)/ serum C3 level at baseline	at week 24
Other	Absolute change rate from baseline in serum C4	(serum C4 level at week 24-serum C4 level at baseline)/ serum C4 level at baseline	at week 24
Other	Absolute change rate from baseline in serum anti-platelet antibody	(serum anti-platelet antibody level at week 24-serum anti-platelet antibody level at baseline)/ serum anti-platelet antibody level at baseline	at week 24
Other	Absolute change rate from baseline in serum Blys	(serum Blys level at week 24-serum Blys level at baseline)/ serum Blys level at baseline. Blys is short for B lymphocyte stimulator.	at week 24
Other	Absolute change rate from baseline in serum APRIL	(serum APRIL level at week 24-serum APRIL level at baseline)/ serum APRIL level at baseline. APRIL is short for a proliferation-inducing ligand.	at week 24
Other	Absolute change rate from baseline in peripheral naive B cell count	(peripheral naive B cell count at week 24-peripheral naive B cell count at baseline)/ peripheral naive B cell count at baseline.	at week 24
Other	Absolute change rate from baseline in peripheral plasma cell count	(peripheral plasma cell count at week 24-peripheral plasma cell count at baseline)/ peripheral plasma cell count at baseline.	at week 24
Other	Absolute change rate from baseline in peripheral plasmablast count	(peripheral plasmablast count at week 24-peripheral plasmablast count at baseline)/ peripheral plasmablast count at baseline.	at week 24
Primary	Overall response (CR + PR) rate	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.	at week 24
Secondary	Overall response (CR + PR) rate	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.	at week 12
Secondary	Rescue treatment rate	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.	at week 24
Secondary	Time to rescue treatment	Time to rescue treatment refers to period duration from the initiation of Telitacicept or placebo (day 1) to rescue treatment.	at week 24
Secondary	Relapse rate	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.	at week 24
Secondary	Time to relapse	Time to relapse refers to period duration from the initiation of Telitacicept or placebo (day 1) to relapse.	at week 24
Secondary	treatment related adverse event	According to the NCI CTCAE 5.0	at week 24
Secondary	treatment related severe adverse event	According to the NCI CTCAE 5.0	at week 24
Secondary	bleeding scale	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.	at week 24