Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus

A Phase I, Multiple-Dose Study to Evaluate the Pharmacokinetics, Safety and Efficacy of Telitacicept in Chinese Subjects With Systemic Lupus Erythematosus (SLE)

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

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Biological: Telitacicept; Drug: standard therapy

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233004
      • The First Affiliated Hospital of Bengbu Medical College
    • Hefei, Anhui, China, 230001
      • The First Affiliated Hospital of University of Science and Technology of China
  • Beijing
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510260
      • The second Affiliated Hospital of Guangzhou Medical University
  • Guangxi
    • Guilin, Guangxi, China, 541001
      • Affiliated Hospital of Guilin Medical University
  • Hebei
    • Baoding, Hebei, China, 071000
      • Affiliated Hospital of Hebei University
    • Shijiazhuang, Hebei, China, 050000
      • The Second Hospital of Hebei Medical University
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
    • Yantai, Shandong, China, 264200
      • Yantai Yuhuangding Hospital
  • Shanxi
    • Taiyuan, Shanxi, China, 030032
      • Shanxi Bethune Hospital
    • Taiyuan, Shanxi, China, 030001
      • The Second Hospital of Shanxi Medical University
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • General Hospital of Tianjin Medical University
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830001
      • The People's hospital of Xinjiang Uygur Autonomous Region
  • Yunnan
    • Kunming, Yunnan, China, 650011
      • The First People's Hospital of Yunnan Province
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The second affiliated hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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..

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telitacicept Arm 1; Telitacicept 80mg, once a week for 24 weeks plus standard therapy	Biological: Telitacicept; subcutaneous injection; Other Names: RC18; Drug: standard therapy; A 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.
Experimental: Telitacicept Arm 2; Telitacicept 160mg, once a week for 24 weeks plus standard therapy	Biological: Telitacicept; subcutaneous injection; Other Names: RC18; Drug: standard therapy; A 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.
Experimental: Telitacicept Arm 3; Telitacicept 160mg, once a week for 12 weeks followed by once every two weeks for another 12 weeks plus standard therapy	Biological: Telitacicept; subcutaneous injection; Other Names: RC18; Drug: standard therapy; A 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.
Experimental: Telitacicept Arm 4; Telitacicept 240mg, once a week for 24 weeks plus standard therapy	Biological: Telitacicept; subcutaneous injection; Other Names: RC18; Drug: standard therapy; A 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.
Experimental: Telitacicept Arm 5; Telitacicept 240mg, once every two weeks for 24 weeks plus standard therapy	Biological: Telitacicept; subcutaneous injection; Other Names: RC18; Drug: standard therapy; A 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax) of Telitacicept	Cmax is defined as peak plasma concentration of Telitacicept	up to 42 days following the last dose of Telitacicept
Time to reach Cmax (tmax) of Telitacicept	tmax is defined as time to reach Cmax of Telitacicept	up to 42 days following the last dose of Telitacicept
Observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval (Ctrough)	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
Average concentration (Cav) of Telitacicept	Average concentration of Telitacicept	up to 42 days following the last dose of Telitacicept
Area under the curve from time zero to last quantifiable concentration (AUC 0-t) of Telitacicept	AUC 0-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
Area under the curve from time zero to tau (AUC 0-tau) of Telitacicept	AUC 0-tau is defined as area under the curve from time zero to tau of Telitacicept	up to 42 days following the last dose of Telitacicept
Terminal elimination rate constant (λz) of Telitacicept	λz is defined as terminal elimination rate constant	up to 42 days following the last dose of Telitacicept
Terminal elimination half-life (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
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Telitacicept	Vz/F is defined as apparent volume of distribution during the terminal phase after extravascular administration of Telitacicept	up to 42 days following the last dose of Telitacicept
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Telitacicept	CL/F is defined as apparent total body clearance of drug from plasma after extravascular administration of Telitacicept	up to 42 days following the last dose of Telitacicept

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants achieving a SLE Responder Index (SRI)	Percentage of subjects with a ≥ 4 point reduction from baseline in SELENA-SLEDAI score, and no worsening (increase of < 0.30 points from baseline) in PGA, and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with baseline.	Week 4, 8, 12, 16, 20, and 24
Percentage of participants achieving a SELENA-SLEDAI improvement of ≥4 points	SELENA-SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105.	Week 4, 8, 12, 16, 20, and 24
Change From Baseline to W24 in patient global assessment (PGA)	PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).	Week 4, 8, 12, 16, 20, and 24
Change From Baseline to W24 in IgG	Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.	Week 4, 8, 12, 16, 20, and 24
Change From Baseline to W24 in IgA	Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.	Week 4, 8, 12, 16, 20, and 24
Change From Baseline to W24 in IgM	Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.	Week 4, 8, 12, 16, 20, and 24
Change From Baseline to W24 in C3	Complement (C3/C4) are proteins that are part of the immune system.	Week 4, 8, 12, 16, 20, and 24
Change From Baseline to W24 in C4	Complement (C3/C4) are proteins that are part of the immune system.	Week 4, 8, 12, 16, 20, and 24
Number of Participants Experiencing Adverse Events (AEs)	Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.	up to 28 days following the last dose of Telitacicept

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Actual): October 25, 2023
• Study Completion (Actual): November 13, 2023

Study Registration Dates

• First Submitted: January 26, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Connective Tissue Diseases; Systemic Lupus Erythematosus; Autoimmune Diseases; Lupus Erythematosus, Systemic; Telitacicept
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: 18C020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No