Clinical trial NCT05247203: Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus
Official title: A Phase I, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Telitacicept in Chinese Subjects With Systemic Lupus Erythematosus (SLE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Keywords: Systemic Lupus Erythematosus
Telitacicept
Pharmacokinetics
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Lead sponsor: RemeGen Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-18
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open-label, phase I study.

Detailed description: The purpose of this study is to evaluate the pharmacokinetics, safety and efficacy of Telitacicept in Chinese patients with systemic lupus erythematosus.

Eligibility criteria: Inclusion Criteria:

1. Subjects who give consent to this study participation and sign informed consent form;
2. Males and females, between the ages of 18 and 65 years old, inclusive, at the screening visit;
3. Diagnosis of SLE as defined by the American College of Rheumatology (ACR) 1997 criteria, with 4 or more of the 11 ACR criteria present;
4. SELENA-SLEDAI score ≥8 points with a clinical SELENA-SLEDAI score ≥6 points if low complement levels and/or anti-ds-DNA antibodies are present at the screening visit;
5. Subjects with unequivocally positive test for anti-nuclear antibody (ANA) and/or anti-ds-DNA serum antibody;
6. Be on a SLE standard treatment regimen (and remain stable) for a period of at least 30 days prior to Day 0. The standard regimen consists of the following medication(s) (alone or in combination)：corticosteroids, anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), other immunosuppressive or immunomodulatory agents including azathioprine, mycophenolate mofetil, cyclophosphamide, methotrexate, leflunomide, tacrolimus, cyclosporine.

Exclusion Criteria:

1. Subjects with severe lupus kidney disease (defined by proteinuria \>6g/24h or serum creatinine \>2.5mg/dL or serum creatinine \>221μmol/L) or active nephritis requiring prohibited medications, or subjects requiring hemodialysis or prednisone (or its equivalent)≥100mg/d for a period of ≥14 days within 8 weeks of Day 0;
2. Central nervous system (CNS) disease associated with lupus or not \[including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), encephalitis, CNS angiitis\] within 8 weeks prior to the screening visit;
3. Laboratory abnormalities including, but not limited to the following:

   1. ALT/AST≥2×upper limit of normal (ULN);
   2. endogenous creatinine clearance rate\<30 mL/min;
   3. white blood cell count\<2.5×10\^9/L;
   4. hemoglobin\<85 g/L;
   5. platelet count\<50×10\^9/L;
4. Active hepatitis or a history of severe liver disease at the screening visit. Positive test for Hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus antibodies (HCVAb). If anti-HBcAb result is positive while HBsAg result is negative, hepatitis B virus (HBV)-(DNA) test will be performed. If HBV-DNA result is negative, the patient is eligible;
5. Subjects with immunodeficiency, uncontrolled severe infection or active/recurrent gastrointestinal ulcers;
6. Pregnant or lactating female subjects or sexually active subjects who refuse to practice the protocol-specified contraception throughout the study;
7. History of allergy to humanized biological products;
8. Subjects who received live vaccine within 28 days of Day 0;
9. Participation in any other investigational study drug trial in the past 28 days or 5 half-lives, whichever was longer, prior to Day 0. Subjects who participated in a clinical trial on B-cell-targeted drug, or tumor necrosis factor inhibitor, or interleukin receptor blocker within 12 months prior to Day 0 would be excluded;
10. Subjects who received other B-cell targeted drugs, such as Belimumab, rituximab or Epratuzumab within 12 months prior to Day 0;
11. Subjects who received tumor necrosis factor inhibitors, interleukin receptor blockers within 12 months prior to Day 0;
12. Subjects who received intravenous immune globulin (IVIG), or high dose prednisone or its equivalents (≥100mg/d) for a period of ≥ 14 days, or plasma exchange within 28 days prior to Day 0;
13. Subjects who received IL-2, Thalidomide, Tripterygium wilfordii or Chinese medicinal preparations containing Tripterygium wilfordii within 28 days prior to Day 0;
14. Subjects with active infections (herpes zoster, HIV infection, active tuberculosis, etc.) at the screening visit;
15. Subjects with depression or suicidal thoughts;
16. Any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol..

Primary outcomes:
measure: Peak plasma concentration (Cmax) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Time to reach Cmax (tmax) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval (Ctrough)
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Average concentration (Cav) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Area under the curve from time zero to last quantifiable concentration (AUC 0-t) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Area under the curve from time zero to tau (AUC 0-tau) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Terminal elimination rate constant (λz) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Terminal elimination half-life (t1/2z) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
measure: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Telitacicept
timeFrame: up to 42 days following the last dose of Telitacicept
Secondary outcomes:
measure: Percentage of participants achieving a SLE Responder Index (SRI)
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Percentage of participants achieving a SELENA-SLEDAI improvement of ≥4 points
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to W24 in patient global assessment (PGA)
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to W24 in IgG
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to W24 in IgA
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to W24 in IgM
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to W24 in C3
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Change From Baseline to W24 in C4
timeFrame: Week 4, 8, 12, 16, 20, and 24
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: up to 28 days following the last dose of Telitacicept
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of University of Science and Technology of China
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital
state: Shanxi
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Ürümqi
country: China
facility: The People's Hospital of Xinjiang Uygur Autonomous Region
state: Xinjiang
city: Kunming
country: China
facility: The First People's Hospital of Yunnan Province
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University
state: Zhejiang
Study officials:
References: