Telitacicept Study in Chinese Subjects With Systemic Lupus Erythematosus

Sponsor

RemeGen Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05247203

Collaborator

(none)

Enrollment

Locations

Arms

18.5

Anticipated Duration (Months)

3.9

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Systemic Lupus Erythematosus	Biological: Telitacicept Drug: standard therapy	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

May 17, 2022

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

Peak plasma concentration (Cmax) of Telitacicept [up to 42 days following the last dose of Telitacicept]
Cmax is defined as peak plasma concentration of Telitacicept
Time to reach Cmax (tmax) of Telitacicept [up to 42 days following the last dose of Telitacicept]
tmax is defined as time to reach Cmax of Telitacicept
Observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval (Ctrough) [up to 42 days following the last dose of Telitacicept]
Ctrough is defined as observed plasma concentration of Telitacicept just prior to the beginning of a dosing interval
Average concentration (Cav) of Telitacicept [up to 42 days following the last dose of Telitacicept]
Average concentration of Telitacicept
Area under the curve from time zero to last quantifiable concentration (AUC 0-t) of Telitacicept [up to 42 days following the last dose of Telitacicept]
AUC 0-t is defined as area under the curve from time zero to last quantifiable concentration of Telitacicept
Area under the curve from time zero to tau (AUC 0-tau) of Telitacicept [up to 42 days following the last dose of Telitacicept]
AUC 0-tau is defined as area under the curve from time zero to tau of Telitacicept
Terminal elimination rate constant (λz) of Telitacicept [up to 42 days following the last dose of Telitacicept]
λz is defined as terminal elimination rate constant
Terminal elimination half-life (t1/2z) of Telitacicept [up to 42 days following the last dose of Telitacicept]
t1/2z is defined as terminal elimination half-life of Telitacicept
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) of Telitacicept [up to 42 days following the last dose of Telitacicept]
Vz/F is defined as apparent volume of distribution during the terminal phase after extravascular administration of Telitacicept
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of Telitacicept [up to 42 days following the last dose of Telitacicept]
CL/F is defined as apparent total body clearance of drug from plasma after extravascular administration of Telitacicept

Secondary Outcome Measures

Percentage of participants achieving a SLE Responder Index (SRI) [Week 4, 8, 12, 16, 20, and 24]
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.
Percentage of participants achieving a SELENA-SLEDAI improvement of ≥4 points [Week 4, 8, 12, 16, 20, and 24]
SELENA-SLEDAI is calculated from 24 individual descriptors; 0 indicates inactive disease and the maximum theoretical score is 105.
Change From Baseline to W24 in patient global assessment (PGA) [Week 4, 8, 12, 16, 20, and 24]
PGA is a visual analog scale scored from 0 to 3 (1=mild, 2=moderate, 3=severe).
Change From Baseline to W24 in IgG [Week 4, 8, 12, 16, 20, and 24]
Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.
Change From Baseline to W24 in IgA [Week 4, 8, 12, 16, 20, and 24]
Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.
Change From Baseline to W24 in IgM [Week 4, 8, 12, 16, 20, and 24]
Immunoglobulins (IgG, IgA and IgM) are proteins produced by plasma cells.
Change From Baseline to W24 in C3 [Week 4, 8, 12, 16, 20, and 24]
Complement (C3/C4) are proteins that are part of the immune system.
Change From Baseline to W24 in C4 [Week 4, 8, 12, 16, 20, and 24]
Complement (C3/C4) are proteins that are part of the immune system.
Number of Participants Experiencing Adverse Events (AEs) [up to 28 days following the last dose of Telitacicept]
Adverse event means any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects who give consent to this study participation and sign informed consent form;
Males and females, between the ages of 18 and 65 years old, inclusive, at the screening visit;
Diagnosis of SLE as defined by the American College of Rheumatology (ACR) 1997 criteria, with 4 or more of the 11 ACR criteria present;
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;
Subjects with unequivocally positive test for anti-nuclear antibody (ANA) and/or anti-ds-DNA serum antibody;
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:

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;
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;
Laboratory abnormalities including, but not limited to the following:
ALT/AST≥2×upper limit of normal (ULN);
endogenous creatinine clearance rate<30 mL/min;
white blood cell count<2.5×10^9/L;
hemoglobin<85 g/L;
platelet count<50×10^9/L;
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;
Subjects with immunodeficiency, uncontrolled severe infection or active/recurrent gastrointestinal ulcers;
Pregnant or lactating female subjects or sexually active subjects who refuse to practice the protocol-specified contraception throughout the study;
History of allergy to humanized biological products;
Subjects who received live vaccine within 28 days of Day 0;
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;
Subjects who received other B-cell targeted drugs, such as Belimumab, rituximab or Epratuzumab within 12 months prior to Day 0;
Subjects who received tumor necrosis factor inhibitors, interleukin receptor blockers within 12 months prior to Day 0;
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;
Subjects who received IL-2, Thalidomide, Tripterygium wilfordii or Chinese medicinal preparations containing Tripterygium wilfordii within 28 days prior to Day 0;
Subjects with active infections (herpes zoster, HIV infection, active tuberculosis, etc.) at the screening visit;
Subjects with depression or suicidal thoughts;
Any condition or circumstance that, in the opinion of the investigator, may compromise the patient's ability to comply with the study protocol..

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China	233004
2	The First Affiliated Hospital of University of Science and Technology of China	Hefei	Anhui	China	230001
3	Peking Union Medical College Hospital	Beijing	Beijing	China	100032
4	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong	China	510260
5	Affiliated Hospital of Guilin Medical University	Guilin	Guangxi	China	541001
6	Affiliated Hospital of Hebei University	Baoding	Hebei	China	071000
7	The Second Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050000
8	Xiangya Hospital, Central South University	Changsha	Hunan	China	410008
9	The Second Xiangya Hospital of Central South University	Changsha	Hunan	China	410011
10	The First Hospital of China Medical University	Shenyang	Liaoning	China	110001
11	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi	China	710061
12	Qilu Hospital of Shandong University	Jinan	Shandong	China	250012
13	Yantai Yuhuangding Hospital	Yantai	Shandong	China	264200
14	The Second Hospital of Shanxi Medical University	Taiyuan	Shanxi	China	030001
15	Shanxi Bethune Hospital	Taiyuan	Shanxi	China	030032
16	General Hospital of Tianjin Medical University	Tianjin	Tianjin	China	300052
17	The People's Hospital of Xinjiang Uygur Autonomous Region	Ürümqi	Xinjiang	China	830001
18	The First People's Hospital of Yunnan Province	Kunming	Yunnan	China	650011
19	The Second Affiliated Hospital of Zhejiang University	Hangzhou	Zhejiang	China	310009