Voclosporin(QL1074): QL1074 23.7 mg BlD will be administered as a fixed dose without the use of therapeutic drugmonitoring. The protocol contains provisions for management of dose based on safety concerns, in particular, BP and renal function,can be managed by dose reduction and temporary of QL1074 to interruption.
Placebo: Placebo softgel capsules, identical to 7.9 mg QL1074, will be provided. The administration plan and dosage management regulations are the same as QL1074.
Study summary
The purpose of this study is to assess the efficacy of QL1074 compared with placebo in achieving renal response after 52 weeks of therapy in subjects with Active Lupus Nephritis.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
Inclusion Criteria:
1. Written informed consent before any study-specific procedures are performed.
2. Male or female subjects with a minimum age of 18 (or legal age of consent if \>18 years) to 75 years of age, inclusive, at the time of screening (Visit 1).
3. Previous diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria (1997)
4. Subjects with evidence of active nephritis, According to the 2018 International Society of Nephrology/Society of Nephropathology (ISN/RPS) classification criteria for lupus nephritis, defined as follows:
* Kidney biopsy result within 2 years prior to screening indicating Class III, IV (alone or in combination with Class V), or Class V LN, Biopsy results must be reviewed with the Investigator to confirm eligibility.
* UPCR of a minimum of ≥1.5 mg/mg for Class III/IV or to a minimum of ≥2 mg/mg for Class V at screening.
* If the subject provides a biopsy report within 2 years but more than 6 months before screening, the UPCR needs to be doubled at least within 6 months before screening.
5. According to the Investigators' evaluation, subject requires high-dose corticosteroids and immunosuppressive therapy.
6. Subject is willing to take oral MMF for the duration of the study, either by continuing current MMF therapy or by initiating it on or before the Baseline Visit.
7. Fertile subjects (both male and female) must agree to use reliable contraception methods with their partners from the time of signing the informed consent form until 3 months after the end of the trial; women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.
Exclusion Criteria:
1. Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/minute/1.73 m2 at screening.
2. urrently taking or planning to use drugs or treatments listed in the Prohibited Drugs (Section 5.5) during the trial, including not completing the required washout.
3. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
4. A previous kidney transplant or planned transplant within study treatment period.
5. Any known hypersensitivity or contraindication to any of the drugs planned to be used (including but not limited to: MMF, Mycophenolate Sodium, Cyclosporine, Voclosporin, Corticosteroids) or any components of these drug products.
6. Current or medical history of:
* The subject has a history of drug abuse or alcohol abuse within 2 years before the screening period;
* Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia 1, but have been treated with conization or loop electrosurgical excision procedure and have had a normal repeat Papanicolaou test are allowed;
* Lymphoproliferative disease or previous total lymphoid irradiation;
* Severe viral infection (e.g., cytomegalovirus, hepatitis B virus, hepatitis C virus) within 3 months of screening; or known HIV infection. Severe viral infection is defined as active disease requiring antiviral therapy;
* Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid;
7. Other known clinically significant active medical conditions, such as:
* Severe cardiovascular disease including congestive heart failure, history of cardiac dysrhythmia, congenital long QT syndrome or Hypertension with poor control (systolic blood pressure ≥165mmHg and/or diastolic blood pressure ≥105mmHg after treatment with 2 or more drugs). QT interval duration corrected for heart rate using method of Fridericia exceeding 480 msec in the presence of a normal QRS interval (\<110 msec) at time of screening will result in exclusion;
* Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin ≥2.5 times the upper limit of normal) at screening and, if abnormal at screening, then confirmed that the levels have returned to \<2.5 times upper limit of normal before randomization;
* Chronic obstructive pulmonary disease or asthma requiring oral steroids;
* Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count \<2.5×109/L; absolute neutrophil count \<1.3×109/L; thrombocytopenia (platelet count \<50×109/L);
* According to the evaluation of the investigator, the subject suffered from active bleeding;
* Patients with infections requiring intravenous antibiotic treatment (antibacterial drugs, antiviral drugs, antifungal drugs, or antiparasitic drugs) during screening;
8. According to the researchers' assessment, the subjects have other congenital or acquired immune diseases (except for SLE and LN), for which the condition or the treatment of the condition may affect the study assessments or outcomes (e.g., scleroderma with significant pulmonary hypertension; any condition for which additional immunosuppression is indicated). Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes (e.g.,Sjögren's syndrome) are not excluded.
9. No vaccines using live vaccines or attenuated live vaccines are allowed in the 4 weeks before the screening and while taking the study treatment.
10. According to the evaluation of the investigators, there have been significant, unstable or poorly controlled physical/mental illnesses or traumas that may affect the progress or results of the trial within the first 6 months of the screening period.
11. Women who are pregnant or breastfeeding.
12. Participated in another drug or device trial within 4 weeks before the screening period or within 5 half-lives of the drug (whichever is longer).
13. The subject has participated in previous clinical trials of Voclosporin, was randomly assigned to a group, and received treatment with the trial drug.
14. According to the assessment of the investigators, there may be conditions that affect the results of the trial or that the risks to the subjects outweigh the benefits.
Primary outcome measure(s)
Number of Participants With Complete Renal Remission at Week 52 — Week 52 The primary efficacy endpoint was the number of subjects showing complete renal response at Week 52. Complete renal response was adjudicated based on blinded data by an independent Clinical Endpoints Committee based on meeting the following criteria: UPCR of ≤0.5 g/g \& eGFR ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of \>20%
Trial sites (10)
Facility
City
Region
Status
The First Affiliated Hospital of Bengbu Medical University
Bengbu
Anhui
Recruiting
The People's Hospital of Bozhou
Bozhou
Anhui
Recruiting
Anhui Provincial Hospital
Hefei
Anhui
Recruiting
The Second Affiliated Hospital of Anhui Medical University
Hefei
Anhui
Recruiting
Chincse PLA General Hosptial
Beijing
Beijing Municipality
Recruiting
Peking University First Hospital
Beijing
Beijing Municipality
Not Yet Recruiting
Fujian Medical University Union Hospital
Fuzhou
Fujian
Recruiting
The First Affiliated Hospital of Dalian Medical University
Dalian
Liaoning
Recruiting
Huashan Hospital
Shanghai
Shanghai Municipality
Recruiting
Heping Hospital Affiliated to Changzhi Medical College
Changzhi
Shanxi
Recruiting
More Qilu Pharmaceutical Co., Ltd. trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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