Systemic Lupus Erythematosus
Conditions
Interventions
Experimental group:Part 1 Dose Escalation:
Dose group 1: 2 mg on day 1 and 6 mg on day 8
Dose group 2: 2 mg on day 1, 20 mg on day 8
Dose group 3: 2 mg on day 1, 60 mg on day 8
Dose group 4: 6 mg on day 1 and 120 mg on day 8
Part 2 is an open-label extension study, which will be conducted at the discretion of the sponsor. In Part 2, the dosing regimen is determined based on
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Patients are eligible for inclusion in the study only if all of the following criteria are met: 1. Aged between 18 and 75 years at the time of signing the informed consent form (ICF); 2. Diagnosis of systemic lupus erythematosus according to the 2019 American College of Rheumatology (ACR) and European Alliance of Association for Rheumatology (EULAR) classification criteria (Aringer et al, 2019); 3. Patients suspected of having lupus nephritis (e.g., proteinuria) must be screened as described in Section 5.1.1 to determine if they are eligible for inclusion in the study as SLE patients with active LN; 4. At screening, patients meet at least two of the following criteria, one of which must be anti-double-stranded deoxyribonucleic acid (anti-dsDNA) positive or anti-Smith antibody: a. Anti-double-stranded DNA antibodies; b. Anti-Smith antibodies; c. Antinuclear antibody (ANA) titer>=1:80; 5. Active SLE: SLEDAI-2K total score >=6 and SLEDAI-2K clinical score >=4 at screening; 6. The patient has a poor response to treatment as judged by the investigator, defined as using any of the following treatments at any time point before screening for at least 3 months, but lacks clinical efficacy or intolerance: antimalarials, mycophenolatemofetil MMF, azathioprine, cyclophosphamide, methotrexate (MTX), leflunomide, tacrolimus, vocyclosporine, cyclosporine, belinumab, terituximab, B Cell-depleting therapies (eg, rituximab, orizolizumab, inipilimab, ofalimumab), aniluzumab, and/or tetracycline; 7. Stable use of any of the following conventional therapies (alone or in combination) through study day D1: a. Methotrexate = 10 weeks prior to screening; b. Hydroxychloroquine =10 weeks prior to screening; c. Chloroquine = 10 weeks prior to screening; d. Leflunomide = 10 weeks prior to screening; Oral prednisone = 2 weeks prior to screening; 8. Any of the following stable medications (alone or in combination) must be discontinued for >=1 week prior to study day D1: a. azathioprine: no more than 2 mg/kg/day at a dose = 10 weeks prior to screening; b. Mycophenolate mofetil: >= 10 weeks prior to screening at a dose not exceeding 3 g/day; c. Mycopheno sodium: >= 10 weeks prior to screening at a dose not exceeding 2.16 g/day; d. Tacrolimus: >= 10 weeks prior to screening according to local standard of care regimen; e. Volosporine: >=10 weeks prior to screening according to local standard of care regimen; f. Cyclosporine: >= 10 weeks prior to screening according to local standard of care regimen. 5.1.1. Additional inclusion criteria for SLE patients with concomitant active LN 1. Active, biopsy-proven hypertrophic ulcerative nephritis type III or IV according to the 2018 International Society of Nephrology/Society of Renal Pathology criteria a. Biopsy must be performed within 1 year prior to or during screening b. Allow the incorporation of V-shapes 2. Proteinuria (24-hour urine protein>=0.75 g/24 hours or urine protein-to-creatinine ratio [UPCR]>=0.75 mg/mg) in a 24-hour urine sample after at least 3 months of treatment with one or more of the following conventional immunosuppressive therapies at any time prior to screening: azathioprine, MMF/mycophenome sodium, cyclophosphamide, calcineurin inhibitors, belinumab, terituximab, and/or anti-CD20 monoclonal antibodies; 3. S
Exclusion criteria
Exclusion criteria: Patients who meet any of the following exclusion criteria must be excluded from the study: 1. Laboratory indicators at screening: a. Peripheral B cell count=2 times ULN ii. Total bilirubin level and alkaline phosphatase > 2 times ULN (or total bilirubin > 2.5 times ULN for patients with Gilbert's syndrome) e. Estimated glomerular filtration rate (estimated glomerular) calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula filtration rate,eGFR)<=60 mL/min/1.73m^2; (If during screening, the original value due to laboratory error is deemed incorrect, a repeat assessment may be performed to confirm eligibility) 2. Patients will be excluded if they are known to have any of the following conditions: a. Any known HIV infection or positive for HIV type 1 or 2 antibodies at screening; b. Positive hepatitis B surface antigen (HBsAg). Patients who are positive for hepatitis B core antibody (HBcAb) must be tested for hepatitis B virus deoxyribonucleic acid (HBV-DNA) to determine their status; If HBV-DNA is positive, the patient should be excluded; If HBV-DNA is negative, the patient can participate in the study; c. Patients with positive hepatitis C antibody must be tested for hepatitis C ribonucleic acid (HCV RNA); If HCV RNA is also positive, the patient should be excluded; If HCV RNA is negative, the patient can participate in the study; d. Active tuberculosis (TB) or lack of documentation of completion of active tuberculosis treatment. If the tuberculosis test (QuantiFERON® -TB Gold Test or T-SPOT) is positive, the patient may have a chest x-ray to rule out latent or active tuberculosis according to local guidelines/standard of care requirements. If the test result is positive and no active tuberculosis is found on chest X-ray, the patient may be allowed to enroll after providing proof of completion of active tuberculosis or latent tuberculosis treatment; ? If the test result is inconclusive, the site should repeat the test; ? A positive test result or two consecutive indeterminate results should be considered a positive result; ? The subsequent negative test result after the indeterminate test result shall be regarded as a negative test result; Occult tuberculosis patients ? Those who have a record of completing anti-tuberculosis therapy before participating in the study can participate in this study; ? Patients with no documented treatment will be considered screen-ineligible for screening; Active infection with novel coronavirus type 2 (SARS-CoV-2), influenza, or respiratory syncytial virus (RSV) confirmed by screening test and asymptomatic for at least 1 week prior to the first dose of cizutami or those who do not have fever and their symptoms improve after stopping antipyretics can be enrolled; f. Patients with confirmed or suspected symptoms and/or signs of infection, temperature of 38°C and above, or antimicrobial use within 1 week prior to the first dose of cizutami; g. Within 3 months prior to the first dose of cizutami, had any of the following infections: Severe infection (requiring hospitalization or systemic antibacterial = for 2 weeks); Opportunistic infections (including but not limited to Pneumoc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of cizutamig; | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the PK of cizutamig in blood; | — |
Countries
China
Contacts
Public ContactZeng Xiaofeng
Peking Union Medical College Hospital
Outcome results
None listed