A Study of Telitacicept in Subjects With Childhood-onset Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This is a multi-center, open-label, phase 1 study.

Detailed Description
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The purpose of this study is to evaluate the pharmacokinetics (PK) of multiple doses of Telitacicept in subjects with childhood-onset systemic lupus erythematosus (cSLE) on a background of standard of care therapy and explore the safety and efficacy of Telitacicept in patients with cSLE.

Official Title
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A Phase 1, Open-label, Multi-center, Multiple-dose Study to Evaluate the Pharmacokinetics of Telitacicept in Subjects With Childhood-onset Systemic Lupus Erythematosus

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Telitacicept 2.5 mg/kg


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Fulfills SLICC 2012 or 2019 EULAR/ACR classification criteria for SLE. 12-17 years of age when signing the informed consent. Parent or legal guardian provided written informed consent. SELENA SLEDAI score ≥ 8 at screening. Serum autoantibodies (ANA and/or anti ds-DNA) tested positive at screening. Have been on a stable standard of care for SLE for at least 30 days prior to randomization. Main Exclusion Criteria: Have received Telitacicept at any time. Have received any of the following therapies within 6 months of baseline: B-cell targeted treatment, e.g., belimumab, rituximab, abatacept, other investigational biologicals. Have received any of the following therapies within 90 days of baseline: anti-TNF or anti-IL-6 therapy, interleukin-1 receptor antagonist, intravenous immunoglobulin (IVIG), plasmapheresis. Have received any of the following therapies within 30 days of baseline: Intravenous cyclophosphamide, non-biological investigational agents (within 30 days of baseline or 5 half-lives, whichever is longer), newly added immunosuppressive/immunomodulatory agent, anti-malarial, NSAID, high-dose prednisone or equivalent (> 1.5 mg/kg/day) or any intramuscular or intravenous steroid. Have received live vaccine within 30 days of baseline. Participated in an interventional clinical trial within 6 months of screening. Active CNS lupus requiring treatment within 60 days of baseline, including seizure, psychosis, organic brain syndrome, cerebrovascular accident, cerebritis or CNS vasculitis. Currently on kidney replacement therapy (hemodialysis, peritoneal dialysis) or in need of such therapy within 90 days of baseline. eGFR<30 mL/min/1.73m2. Acute severe nephritis. History of vital organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. Significant unstable or uncontrolled acute or chronic diseases (cardiovascular, lung, hematology, gastrointestinal, liver, renal, neurologic, malignancy or infectious disease) that could be explained by causes other than SLE. History of malignant neoplasm in the past 5 years. Primary immune deficiency. Acute or chronic infections requiring treatment. HIV/HCV/HBsAg/HBcAb positive. Tuberculosis. Have planned surgery, laboratory abnormalities, other diseases or conditions that, in the opinion of the investigator, makes the subject unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telitacicept 2.5 mg/kg<br>Telitacicept 2.5 mg/kg | Biological: Telitacicept 2.5 mg/kg<br>* Subjects will be given Telitacicept 2.5 mg/kg (with a maximum dose of 160 mg) subcutaneously once a week plus SOC for 12 weeks.<br>* Other names: RC18;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Telitacicept | Cmax is defined as peak plasma concentration of Telitacicept | up to 42 days following the last dose of Telitacicept | 
| tmax of Telitacicept | tmax is defined as time to reach Cmax of Telitacicept | up to 42 days following the last dose of Telitacicept | 
| Ctrough of Telitacicept | Ctrough is defined as observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval | up to 42 days following the last dose of Telitacicept | 
| Cav of Telitacicept | Average concentration of Telitacicept | up to 42 days following the last dose of Telitacicept | 
| AUC0-t of Telitacicept | AUC0-t is defined as area under the curve from time zero to last quantifiable concentration of Telitacicept | up to 42 days following the last dose of Telitacicept | 
| t1/2z of Telitacicept | t1/2z is defined as terminal elimination half-life of Telitacicept | up to 42 days following the last dose of Telitacicept | 
| λz of Telitacicept | λz is defined as terminal elimination rate constant | up to 42 days following the last dose of Telitacicept | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SLE Responder Index 4 (SRI 4) | SRI 4 is defined as a. SELENA-SLEDAI score reduced from baseline by at least 4 points; b. no new BILAG A or no more than 1 BILAG B compared to baseline; c. physician's global assessment (PGA) increased from baseline by less than 0.3 points. | Week 4, Week 8, Week 12 | 
| Proportion of subjects with SELENA-SLEDAI score reduced from baseline by at least 4 points. | The SELENA-SLEDAI is a tool for measuring the activity of systemic lupus. The total score ranges from 0-105, with a higher score representing a more significant degree of disease activity. | Week 4, Week 8, Week 12 | 
| Change from baseline in PGA. | The PGA is a visual analog scale scored from 0 to 3. A score of 1 corresponds to mild lupus disease activity. A score of 2 correlates with moderate disease activity and a score of 3 with severe disease activity. | Week 4, Week 8, Week 12 | 
| Change From Baseline in IgG | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. | Week 4, Week 8, Week 12 | 
| Change From Baseline in IgA | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. | Week 4, Week 8, Week 12 | 
| Change From Baseline in IgM | Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells. | Week 4, Week 8, Week 12 | 
| Change From Baseline in C3 | Complement (C3/C4) are proteins that are part of the immune system. | Week 4, Week 8, Week 12 | 
| Change From Baseline in C4 | Complement (C3/C4) are proteins that are part of the immune system. | Week 4, Week 8, Week 12 | 
| Incidence of AEs | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. | up to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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systemic lupus erythematosus, pediatrics, PK