Study to Assess Efficacy and Safety of HSK39297 Tablets in Patients With LN

Haisco Pharmaceutical Group

Status and phase: Enrolling; Phase 2

Conditions: Lupus Nephritis (LN)

Treatments: Drug: HSK39297 300mgQD; Drug: Placebo; Drug: HSK39297 200mgQD

Study type: Interventional

Funder types: Industry

Identifiers

NCT07363460

HSK39297-205

Details and patient eligibility

About

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

Enrollment: 105 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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 criterias);

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).

Exclusion criteria

1. The subject has previously failed to respond to treatment with MMF or other mofetil mycophenolate drugs, as assessed by the investigator.
2. Allergy to the investigational product or MMF, or contraindications to MMF and glucocorticoids.
3. Currently receiving or requiring administration of any drug listed in Section 5.7.2.2 "Prohibited Concomitant Medications" during the study period.
4. Receiving systemic glucocorticoid therapy for reasons other than systemic lupus erythematosus or lupus nephritis at screening (dose > 10 mg/day prednisone or equivalent; dosage conversion details see Appendix 4).
5. Received treatment with other investigational drugs within 30 days prior to screening or within 5 half-lives (whichever is longer).
6. Presence of rapidly progressive glomerulonephritis at screening (eGFR decline exceeding 50% within 3 months, or less than 50% but with rapid decline risk assessed by the investigator); renal biopsy showing crescents occupying more than 50% of glomeruli, or glomerulosclerosis exceeding 60%, or tubular atrophy/interstitial fibrosis exceeding 60%.
7. Presence of severe extra-renal manifestations of systemic lupus erythematosus at screening, including but not limited to severe pulmonary hypertension (WHO classification IV or higher), severe pulmonary interstitial fibrosis, severe myocarditis, severe heart failure (NYHA classification IV), or active central nervous system lupus.
8. Major, unstable, or uncontrolled acute or chronic diseases affecting various systems (e.g., cardiovascular, respiratory, hematological, gastrointestinal, hepatic, renal, neurological systems) within 6 months prior to screening or at screening that may affect study results or place the subject at high risk, excluding those caused by SLE.
9. History of other autoimmune diseases.
10. History of any of the following infections:

1) History of encapsulated bacterial infection (e.g., Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae) within 1 year prior to screening; 2) Active tuberculosis at screening; history of active tuberculosis within 2 years prior to screening; history of active tuberculosis currently cured but assessed by the investigator to be at risk for reactivation; positive interferon-gamma release assay with determination by the investigator or consulting specialist physician that it represents latent tuberculosis requiring prophylactic anti-tuberculosis treatment; 3) History of other active infections requiring antimicrobial treatment within 3 months prior to screening.

11. History of major organ (heart, lung, kidney, liver) transplantation or hematopoietic stem cell/bone marrow transplantation, or planned for transplantation.

12. Currently undergoing regular hemodialysis or planning to undergo hemodialysis during the study period.

13. History of gastrointestinal surgery that may significantly affect drug absorption, distribution, metabolism, and excretion, or history of severe gastrointestinal disease, or difficulty in swallowing, frequent vomiting leading to difficulty in eating or taking medication.

14. Diagnosis of malignancy within 5 years prior to screening, excluding basal cell carcinoma of the skin, papillary thyroid carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.

15. Major surgical procedures within 6 months prior to screening. 16. Laboratory tests at screening meet any of the following criteria:

1. Estimated Glomerular Filtration Rate (eGFR) < 30 ml/min/1.73m² (calculated by CKD-EPI 2021 formula, see Appendix 5);
2. Hematology: neutrophils < 1 × 10⁹/L; leukocytes < 2 × 10⁹/L; hemoglobin < 80 g/L; platelets < 50 × 10⁹/L;
3. Liver function: Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 3 × ULN; Total Bilirubin (TBIL) ≥ 2 × ULN;
4. Hepatitis B virus surface antigen (HBsAg) positive, or HBsAg negative but Hepatitis B virus core antibody (HBc-Ab) positive with HBV-DNA detection result higher than the quantitative lower limit; Hepatitis C virus antibody (HCV-Ab) positive;
5. Human Immunodeficiency Virus antibody (HIV-Ab) positive. 17. Pregnant or lactating female subjects at screening. 18. Other situations deemed unsuitable for participation by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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105 participants in 3 patient groups, including a placebo group

200mg QD

Active Comparator group

Description:

Patients take double-blind HSK39297 tablets 200mg for 52 weeks

Treatment:

Drug: HSK39297 200mgQD

300mg QD

Active Comparator group

Description:

Patients take double-blind HSK39297 tablets 300mg for 52 weeks

Treatment:

Drug: HSK39297 300mgQD

Placebo

Placebo Comparator group

Description:

Patients take double-blind placebo for 52 weeks

Treatment:

Drug: Placebo