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

NCT ID: NCT06406205

Last Updated: 2024-05-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-25
• Study Completion Date: 2028-06-30

Brief 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.

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.

Conditions

Lupus Nephritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Voclosporin（QL1074）

oral, 23.7 mg twice daily (BID)，52 weeks Drug: Voclosporin calcineurin inhibitor Other Names: QL1074

Group Type: EXPERIMENTAL

Voclosporin（QL1074）

Intervention Type: DRUG

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 Oral Capsule

Voclosporin placebo, oral, 3 capsules twice daily (BID)，52 weeks Drug: Placebo Oral Capsule matching placebo capsule

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo softgel capsules, identical to 7.9 mg QL1074, will be provided. The administration plan and dosage management regulations are the same as QL1074.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Qilu Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guangyan Cai, MD

Role: STUDY_CHAIR

Chincse PLA General Hosptial

Locations

The First Affiliated Hospital of Bengbu Medical University

Bengbu, Anhui, China

Site Status: RECRUITING

The People's Hospital of Bozhou

Bozhou, Anhui, China

Site Status: RECRUITING

Anhui Provincial Hospital

Hefei, Anhui, China

Site Status: RECRUITING

The Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Site Status: RECRUITING

Chincse PLA General Hosptial

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status: NOT_YET_RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status: RECRUITING

The First Affiliated Hospital of Dalian Medical University

Dalian, Liaoning, China

Site Status: RECRUITING

Huashan Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Heping Hospital Affiliated to Changzhi Medical College

Changzhi, Shanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Feng Guo

Role: CONTACT

feng11.guo@qilu-pharma.com

0531-55821177

Facility Contacts

Yongjun Mei

Role: primary

Yuhui zhang

Role: primary

zhu chen

Role: primary

Long Qian

Role: primary

Guangyan CAI, MD

Role: primary

010-68130297

Minghui zhao

Role: primary

Lixin Wei

Role: primary

Hongli Lin

Role: primary

Jing Chen

Role: primary

Pengfei zhang

Role: primary

Other Identifiers

QLG1074-301

Identifier Type: -

Identifier Source: org_study_id