A Study of QLG1074 Combined With Background Therapy in Subjects With Active Lupus Nephritis

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy and Safety of QLG1074 With Placebo in Achieving Renal Remission in Subjects With Active Lupus Nephritis

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.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Voclosporin（QL1074）; Drug: Placebo

Detailed Description

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
• Enrollment (Estimated): 270
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Feng Guo; Phone Number: 0531-55821177; Email: feng11.guo@qilu-pharma.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medical University
      • Contact: Yongjun Mei
    • Bozhou, Anhui, China
      • Recruiting
      • The People's Hospital of Bozhou
      • Contact: Yuhui zhang
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provincial Hospital
      • Contact: Zhu Chen
    • Hefei, Anhui, China
      • Recruiting
      • The Second Affiliated Hospital of Anhui Medical University
      • Contact: Long Qian
  • Beijing
    • Beijing, Beijing, China
      • Not yet recruiting
      • Peking University First Hospital
      • Contact: Minghui Zhao
    • Beijing, Beijing, China
      • Recruiting
      • Chincse PLA General Hosptial
      • Contact: Guangyan CAI, MD; Phone Number: 010-68130297
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Fujian Medical University Union Hospital
      • Contact: Lixin Wei
  • Liaoning
    • Dalian, Liaoning, China
      • Recruiting
      • The First Affiliated Hospital of Dalian Medical University
      • Contact: Hongli Lin
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Huashan Hospital
      • Contact: Jing Chen
  • Shanxi
    • Changzhi, Shanxi, China
      • Recruiting
      • Heping Hospital Affiliated to Changzhi Medical College
      • Contact: Pengfei zhang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Voclosporin（QL1074）; oral, 23.7 mg twice daily (BID)，52 weeks Drug: Voclosporin calcineurin inhibitor Other Names: QL1074	Drug: 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 Comparator: Placebo Oral Capsule; Voclosporin placebo, oral, 3 capsules twice daily (BID)，52 weeks Drug: Placebo Oral Capsule matching placebo capsule	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number 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%	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in UPCR	Change from baseline by visit in Urine Protein Creatinine Ratio. Baseline is the average of two pre-randomisation values.	Baseline and Weeks 2, 4, 8, 12, 16, 16, 20, 24, 30, 36, 42, 48 and 52.
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	Week 24 and 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.	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	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.	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.	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.	Week 24
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.	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	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.	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.	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.	Week 24 and Week 52

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Study Chair: Guangyan Cai, MD, Chincse PLA General Hosptial

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: May 5, 2024
• First Posted (Actual): May 9, 2024

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 5, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis; Lupus Nephritis
• Other Study ID Numbers: QLG1074-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No