Lupus Nephritis (LN)
Conditions
Brief summary
A double-blind,placebo controlled,randomized Phase 2 study to evaluate the safety and tolerability of once-daily, oral administration of 200 or 300 mg HSK39297 tablets versus placebo in Patients With Lupus Nephritis
Interventions
DRUGHSK39297 200mgQD
once daily, oral administration of HSK39297 tablets 200mg from Day 1 to Week 52.
DRUGHSK39297 300mgQD
once daily, oral administration of HSK39297 tablets 300mg from Day 1 to Week 52.
DRUGPlacebo
once daily, oral administration of placebo from Day 1 to Week 52.
Sponsors
Haisco Pharmaceutical Group Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Understand and comply with the research requirements, voluntarily participate in the research and sign the informed consent form before starting the relevant procedures; 2. Age ≥ 18 and \< 75 years old at screening, gender not limited; 3. Positive anti-ANA antibody and/or anti-dsDNA antibody (research center); 4. Pathological type of active III or IV lupus nephritis confirmed by renal biopsy within 12 months before screening, with or without type V (adopting the 2003 International Society of Nephrology/Renal Pathology Working Group's lupus nephritis pathological classification criteria, see Appendix 2; for recurrent subjects, the investigator assesses whether a repeat renal biopsy is necessary; renal biopsy is conducted after confirming that the subject meets all other inclusion criterias and does not meet the
Exclusion criteria
s); 5. Evidence of active lupus nephritis exists, and the investigator assesses that it is necessary to receive glucocorticoid combined with MMF treatment. Active lupus nephritis must meet the following two criterias: a) Proteinuria: a) At screening: 24h-UPCR ≥ 1g/g or FMV-UPCR ≥ 1g/g or FMV-UACR ≥ 0.5g/g; b) Before randomization: 24h-UPCR ≥ 1g/g (central laboratory); b) At screening: SLEDAI-2000 ≥ 8; 6. First onset or recurrence of lupus nephritis (for subjects who have received MMF treatment previously and have experienced recurrence, the investigator and the sponsor jointly assess the benefit based on the study's medication regimen to determine whether they can be enrolled); 7. Female subjects with reproductive capacity \[excluding those who have undergone surgical sterilization (hysterectomy, bilateral tubal ligation, bilateral oophorectomy) at least 6 weeks prior to screening or who are postmenopausal (defined as having no menstruation for 12 months, with no other medical cause)\]; a negative pregnancy test must be confirmed during the screening period. The subject must agree not to attempt pregnancy and not to donate oocytes from the date of signing the informed consent form until at least 30 days after the last administration of investigational product, and must use effective contraception; male subjects must agree not to donate sperm for at least 90 days from the date of signing the informed consent form until at least 90 days after the last administration of investigational product, and must use highly effective contraception with their female partners (see Appendix 3).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ratio of 24h-UPCR compared to Baseline | 24 weeks | Urine Protein Creatinine Ratio |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion achieving CRR/PRR | 12,24,52 weeks | Complete Renal Response,Partial Renal Response |
| Proportion achieving CRR/PRR without renal recurrence | 24,52 weeks | Complete Renal Response,Partial Renal Response |
| Proportion achieving CRR/PRR with glucocorticoid ≤ 5mg/d | 24,52weeks | Complete Renal Response,Partial Renal Response |
| Proportion achieving 25%/50% reduction in 24h-UPCR | 12,24,52 weeks | Urine Protein Creatinine Ratio |
| Time to first achievement of CRR, 25%/50% proteinuria reduction | from baseline to 52 weeks | Complete Renal Response |
| Duration of sustained CRR/PRR | from baseline to 52 weeks | Complete Renal Response,Partial Renal Response |
| Change in 24h-UPCR from baseline. | from baseline to 52 weeks | Urine Protein Creatinine Ratio |
| Change in eGFR from baseline | 12,24,52 weeks | Estimated glomerular filtration rate |
| Proportion with Glucocorticoid dose ≤ 5mg/d | 24,52 weeks | — |
| Annualized slope of eGFR | 52 weeks | Estimated glomerular filtration rate |
| Change in SLEDAI-2000 (Systemic lupus erythematosus disease activity index 2000，SLEDAI-2000)total score from baseline | 12, 24, 52 weeks | SLEDAI-2000 scale ranges form 0 to 105 score. The higher scores indicate a higher disease activity level of the subject's systemic lupus erythematosus . |
| Incidence and severity of adverse events (AEs) | 52 weeks | — |
| Pharmacokinetic characteristics(Cmax) of HSK39297 tablets in plasma. | 52 weeks | — |
| Pharmacokinetic characteristics(Cmin) of HSK39297 tablets in plasma. | 52 weeks | — |
| Pharmacokinetic characteristics(Cavg) of HSK39297 tablets in plasma. | 52 weeks | — |
| Pharmacokinetic characteristics(Tmax) of HSK39297 tablets in plasma. | 52 weeks | — |
| Pharmacokinetic characteristics(AUC0-τ) of HSK39297 tablets in plasma. | 52 weeks | — |
| Changes from baseline of pharmacodynamic indicators(Ap) | 52 weeks | — |
| Changes from baseline of pharmacodynamic indicators(Bb) | 52 weeks | — |
| Changes from baseline of pharmacodynamic indicators(sC5b-9) | 52 weeks | — |
| Changes from baseline in biological markers （C3）reflecting immunological activity of lupus nephritis | 52 weeks | — |
| Changes from baseline in biological markers （C4）reflecting immunological activity of lupus nephritis | 52 weeks | — |
| Changes from baseline in biological markers （anti-dsDNA antibody）reflecting immunological activity of lupus nephritis | 52 weeks | — |
| Change in FACIT-F (Functional Assessment of Chronic Illness Therapy-Fatigue)score from baseline | 52 weeks | FACIT-F scale ranges from 0 to 52 score,and the higher scores indicate a better condition of the subject and less fatigue. |
Countries
China
Contacts
CONTACTfangqiong Li
PRINCIPAL_INVESTIGATORbicheng Liu
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine
Outcome results
None listed