Efficacy and Safety of Telitacicept in the Treatment of Systemic Sclerosis

Diffuse Cutaneous Systemic Sclerosis Clinical Trial

Official title:

The Efficacy and Safety of Telitacicept in the Treatment of Early Diffuse Cutaneous Systemic Sclerosis: A Multicenter, Open-label, Randomized Controlled Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06375005
• Other study ID #: 2024-0381
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: JING XUE, PhD
• Phone: 86-13858121751
• Email: jingxue[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a prospective, open-label, randomized, controlled, multi-center clinical trial. The aim of this study is to investigate the efficacy and safety of Telitacicept in adults with early diffuse cutaneous systemic sclerosis (dcSSc), with Mycophenolate Mofetil (MMF) administered as a background treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 38
• Est. completion date: December 31, 2026
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Men or women aged 18-70 years old.

• Systemic sclerosis, as defined by ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) 2013 criteria.

• dcSSc (diffuse cutaneous systemic sclerosis) according to the LeRoy criteria.

• Disease duration of = 18 months (defined as time from the first non-Raynaud's phenomenon manifestation).

• = 10 mRSS units at the screening visit.

• Negative serum pregnancy test in a woman of childbearing potential at the screening visit.

• Ability to render informed consent in accordance with institutional guidelines.

Exclusion Criteria:

• Limited scleroderma.

• Disease duration of greater than 3 years.

• Rheumatic autoimmune disease other than SSc.

• Systemic sclerosis-like illness associated with environmental agents such as vinyl chloride, or bleomycin.

• Any prior history of renal crisis.

• Intermediate- or high-risk pulmonary arterial hypertension.

• Pulmonary disease with FVC < 50% of predicted or DLCO (hemoglobin-corrected) < 40% of predicted at screening or requires oxygen therapy.

• Underwent major surgery within 8 weeks prior to randomization or planned major surgery during the trial period.

• Use of immunosuppressive therapies, including methotrexate, azathioprine, hydroxychloroquine, leflunomide, tacrolimus, sirolimus, and mycophenolate mofetil within 4 weeks prior to randomization, and cyclophosphamide within 3 months prior to randomization.

• Use of other anti-fibrotic agents, including colchicine, D-penicillamine, thalidomide, nintedanib, pirfenidone, tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib) within 4 weeks prior to randomization.

• Use of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily, or intravenous and intramuscular corticosteroid injections within 4 weeks prior to randomization.

• Use of Intravenous Immunoglobulin (IVIG) within 12 weeks within 4 weeks prior to randomization.

• Prior use of belimumab, rituximab, or other B-Cell depleting therapies ever.

• Use of other biologics or small molecule targeted therapies, including anakinra within 1 week prior to randomization, ixekizumab within 2 weeks prior to randomization, and infliximab, certolizumab pegol, golimumab, adalimumab, abatacept, tocilizumab within 8 weeks prior to randomization, and janus kinase inhibitors within 2 weeks prior to randomization.

• Prior use of other cell depletion therapies.

• Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as severe central nervous system disease,severe heart failure, arrhythmia, unstable atherosclerotic cardiovascular disease, severe GI involvement, severe hypertension or severe diabetes.

• Abnormal results in hepatitis B or hepatitis C testing indicating active or chronic infection.

• Active tuberculosis (TB) or latent TB infection.

• Seropositive for human immunodeficiency virus (HIV) or known history of HIV infection.

• Known active bacterial, viral, fungal, mycobacterial, or other infection,including major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening.

• Primary or secondary immunodeficiency.

• IgA deficiency (<10 mg/dL) or IgG deficiency (<400 mg/dL).

• Participation in another clinical research study involving the evaluation of another investigational drug within 3 months of entry into this study.

• Any of the following at the screening visit: Hemoglobin <8.0 g/dL; WBC <3 x 10^9/L; Neutrophil <1.5 x 10^9/L; platelets <75 x 10^9/L; serum ALT or AST > 1.5 x ULN; TBil > ULN; eGFR < 40mL/min/1.73m^2.

• Malignant disease within 5 years prior to screening, with the exception of excised/cured local basal or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix;

• Immunization with a live/attenuated vaccine within 4 weeks prior to randomization.

• Pregnant or breast feeding women or women of childbearing potential not willing to use adequate contraception.

• History of allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.

• Immunization with a live/attenuated vaccine within 4 weeks prior to randomization.

• Patients anticipated to be non-compliant with the protocol requirements or expected not to complete the trial as planned (e.g., those with psychiatric disorders, history of alcohol abuse, drug abuse, or substance misuse).

Related Conditions & MeSH terms

• Diffuse Cutaneous Systemic Sclerosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis

Intervention

Drug:
• Telitacicept
Telitacicept is fusion protein comprising a recombinant transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) receptor fused to the fragment crystallizable (Fc) domain of human immunoglobulin G (IgG). Telitacicept binds to and neutralizes the activity of two cell-signalling molecules, B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby suppressing the development and survival of plasma cells and mature B cells. Telitacicept will be subcutaneously injected at a dose of 160mg per week, lasting for 48 weeks.
• Mycophenolate Mofetil
All patients will receive background therapy with Mycophenolate Mofetil (MMF), administered orally at a dose of 0.5g twice daily for 48 weeks.

Locations

Country	Name	City	State
China	Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital, Zhejiang University School Of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Changxing People's Hospital	Huzhou	Zhejiang
China	The First Hospital of Jiaxing	Jiaxing	Zhejiang
China	Ningbo First Hospital	Ningbo	Zhejiang
China	Huashan Hospital of Fudan University	Shanghai	Shanghai
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Affiliated Hospital of Yangzhou University	Yangzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 48	Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.	Baseline, Week 48
Primary	Percentage of Participants With Treatment-related Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Week 52
Secondary	Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 24	Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement.	Baseline, Week 24
Secondary	Percentage of Participants Who Improved in Modified Rodnan Skin Score (mRSS) by =20%, =40%, =60% From Baseline to Week 24 and Week 48	Skin thickness was assessed by the mRSS. The mRSS was rated with scores ranging from 0 (normal) to 3 (severe skin thickening) across 17 different sites. The total score was the sum of the individual skin scores in the 17 body areas (e.g., face, hands, fingers; proximal area of the arms, distal area of the arms, thorax, abdomen; proximal area of the legs, and distal area of the legs, feet), giving a range of 0-51 units and had been validated for participants with systemic sclerosis (SSc). A negative change from baseline showed improvement. Percentage of participants who achieved improvement in mRSS by =20%, =40%, =60% from baseline to week 24 and week 48 were reported.	Baseline, Week 24 and 48
Secondary	American College of Rheumatology Composite Response Index for Systemic Sclerosis (ACR-CRISS) and Revised ACR-CRISS at Week 24 and 48	CRISS forms a composite response index consisting of SSc-related organ involvement and the following five variables: mRSS, FVC percent predicted, physician's and patient's global assessments, and HAQ-DI score. The resulting index is a 2-step process that captures clinically meaningful worsening of internal organ involvement and the core variables that show change.	Week 24 and 48
Secondary	Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted at Week 24 and Week 48	FVC is pulmonary function test and will be conducted as per the study Pulmonary Function Manual, which is based on the American Thoracic Society/European Respiratory Society (ATS/ERS) Consensus Statement. FVC is the maximum amount of air exhaled from the lungs after taking the deepest breath possible. Negative change in FVC percent predicted indicates worsening.	Week 24 and 48
Secondary	Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Percent Predicted (Corrected For Hemoglobin) at Week 24 and Week 48	Diffusing capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. It is used to determine the severity of lung disease. DLCO for a given individual is compared to reference or predicted values.	Week 24 and 48
Secondary	Change From Baseline in Patient's Global Assessment at Week 24 and Week 48	Patient global assessment for overall disease represents the patient's assessment of the patient's global scleroderma on a 0 (excellent) -10 (extremely poor) Likert scale. Higher score means worse outcome.	Baseline, Week 24 and 48
Secondary	Change From Baseline in Physician's Global Assessment at Week 24 and Week 48	This assessment represents the physician's assessment of the patient's current disease activity on a 0 (excellent) -10 (extremely poor) Likert scale. Higher score means worse outcome.	Baseline, Week 24 and 48
Secondary	Change From Baseline in Short Form-36 (SF-36) Questionnaire at Week 24 and Week 48	The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health.	Baseline, Week 24 and 48
Secondary	Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 24 and Week 48	The HAQ-DI is a composite measure from which a 'Standard Disability Index' score can be computed to assess a patient's disability level. Generally, a score of 0-1 represents mild to moderate difficulty, 1-2 moderate to severe disability and 2-3 severe to very severe disability. The HAQ-DI comprises 20 items that assess patient abilities across 8 functional activities: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item is rated on a 4-point scale: 0=Without ANY difficulty, 1=With SOME difficulty, 2=With MUCH difficulty, 3=UNABLE to do. The 8 scores of the 8 sections are summed and divided by 8. In the event that one section is not completed by a subject then the summed score would be divided by 7. The final overall HAQ-DI score ranges from 0 to 3 and positive change indicates worse health-related quality of life (HRQoL).	Baseline, Week 24 and 48
Secondary	Change From Baseline in Physical Function Assessed by Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) at Week 24 and Week 48	SHAQ-DI assessed five scleroderma-specific visual analogue scale (VAS) items to explore the impact of participant's disease. These items were developed to measure the effect of scleroderma on five elements of disease that could have a great impact on a participant's daily activities. Each VAS item was rated separately (0-100 millimeters [mm]), with higher scores indicating more severe disease. The five items were: 1) intestinal disease, 2) breathing problem, 3) Raynaud syndrome, 4) finger ulcers, and 5) overall disease.	Baseline, Week 24 and 48
Secondary	Change From Baseline in Tender Joint Counts at Week 24 and Week 48	28 joints are assessed for tenderness (positive or negative). The number of tender joint counts ranges from 0 to 28. A higher number indicates worse outcome.	Baseline, Week 24 and 48
Secondary	Change From Baseline in Swollen Joint Counts at Week 24 and Week 48	28 joints are assessed for swelling (positive or negative). The number of swollen joint count ranges from 0 to 28. A higher number indicates worse outcome.	Baseline, Week 24 and 48
Secondary	Change From Baseline in Digital Ulcer Counts at Week 24 and Week 48	Digital ulcers refer to lesions (on the finger or distal to the metacarpophalangeal joint) with loss of surface epithelisation and a visually discernible depth.	Baseline, Week 24 and 48