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.
The aim of the current study is to investigate whether QL1074, added to the standard of care treatment in active lupus nephritis (LN), is able to reduce disease activity over a treatment period of 52 weeks. The background therapy will be mycophenolate mofetil (MMF) and initial treatment with IV methylprednisolone, followed by a reducing course of oral corticosteroids. Subjects with active LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria (as measured by Urine Protein Creatinine Ratio (UPCR)) while demonstrating an acceptable safety profile.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
270
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 softgel capsules, identical to 7.9 mg QL1074, will be provided. The administration plan and dosage management regulations are the same as QL1074.
The First Affiliated Hospital of Bengbu Medical University
Bengbu, Anhui, China
RECRUITINGThe People's Hospital of Bozhou
Bozhou, Anhui, China
RECRUITINGNumber of Participants With Complete Renal Remission at 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%
Time frame: Week 52
Time to Urine Protein Creatinine Ratio of ≤0.5 g/g(Number of Days)
Time in days to reduction in Urine Protein Creatinine Ratio to decrease to 0.5 g/g or less.
Time frame: 52 Weeks
Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 g/g or Less
Number of Participants With Reduction in Urine Protein Creatinine Ratio to 0.5 g/g or Less
Time frame: 52 Weeks
Number of Subjects With Partial Renal Response at Week 52
Number of subjects with partial Renal Response (defined as a 50% reduction in UPCR from baseline) at Week 52. Baseline UPCR is the average of 2 pre-randomisation values.
Time frame: Week 52
Time to 50% Reduction in UPCR (Number of Days)
Time in days to reduction in Urine Protein Creatinine Ratio to decrease by 50% compared to baseline. Baseline is the average of two pre-randomisation values.
Time frame: 52 Weeks
Number of Subjects With Partial Renal Response at Week 24
Number of subjects with partial Renal Response (defined as a 50% reduction in UPCR from baseline) at Week 24. Baseline UPCR is the average of 2 pre-randomisation values.
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Anhui Provincial Hospital
Hefei, Anhui, China
RECRUITINGThe Second Affiliated Hospital of Anhui Medical University
Hefei, Anhui, China
RECRUITINGChincse PLA General Hosptial
Beijing, Beijing Municipality, China
RECRUITINGPeking University First Hospital
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGFujian Medical University Union Hospital
Fuzhou, Fujian, China
RECRUITINGThe First Affiliated Hospital of Dalian Medical University
Dalian, Liaoning, China
RECRUITINGHuashan Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGHeping Hospital Affiliated to Changzhi Medical College
Changzhi, Shanxi, China
RECRUITINGTime frame: Week 24
Number of Subjects With Renal Response With Low Dose Steroids
Programmed Renal Response whilst on low dose steroids (\<2.5 mg/day) for the preceding 8 Weeks at Weeks 24 and 52
Time frame: Week 24 and Week 52
Change From Baseline in UPCR
Change from baseline by visit in Urine Protein Creatinine Ratio. Baseline is the average of two pre-randomisation values.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Proportion of subjects experiencing a confirmed 30% decrease or more fom baseline in eGFR at each timepoint
Number of subjects with a 30% or more decrease in estimated glomerular filtration rate compared to baseline at each visit time point that meets diagnostic criteria.
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Change from baseline by visit in Serum Creatinine, Urine Protein, and estimated Glomerular Filtration rate.
Change from baseline by visit in Serum Creatinine, Urine Protein, and estimated Glomerular Filtration rate. eGFR is corrected to a maximum value of 90 mL/min/1.73 m2
Time frame: Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
Change From Screening in Immunology Parameters (Complement 3 (C3), C4, and Anti-Double-Stranded DNA)
Change from baseline by visit in Immunology Parameters (Complement 3 (C3), C4, and Anti-Double-Stranded DNA). The immunological baseline data is the numerical value during the screening period.
Time frame: Week 24 and Week 52
Change From Baseline in Patient Reported Outcomes
Health-related quality of life (HRQoL) information was collected using the Short Form Health Survey (SF-36) HRQoL assessment and the LupusPRO (v1.7) assessment. The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. Scoring ranges from 0 to 100 with higher scores reflecting better health. LupusPro assessment is a patient-reported questionnaire regarding the effect of lupus or its treatment on the patient's health, quality of life, and the medical care received related to lupus. The questionnaire consists of 43 questions within 8 HRQOL domains and 4 Non-HRQoL domains. Scores range from 0 to 100 with higher scores reflecting better quality of life.
Time frame: Week 12, Week 24 and Week 52
Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA - SLEDAI)
The SELENA-SLEDAI tool is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with lupus. A patient's SELENA-SLEDAI total score is the sum of all marked lupus related descriptors (seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, vasculitis, arthritis, myositis, urinary casts, hematuria, proteinuria, pyuria, new rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, increased DNA binding, fever, thrombocytopenia, leukopenia). A total score can fall between 0 and 105, with a higher score representing a more significant degree of disease activity.
Time frame: Week 24 and Week 52