Safety and Efficacy of Combination Belimumab and Voclosporin in the Treatment of Proliferative Forms of Lupus Glomerulopathy: Synergy Trial

NCT07225387 | Recruiting Phase 4 FDA Drug

• 1 other identifier: NephroNet-24-009
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

This is a Phase IV, open-label, randomized trial to determine whether the combination of Belimumab (BEL) and Voclosporin (VCS), plus background therapy with Mycophenolate Mofetil (MMF), improves the proportion of patients with proliferative lupus nephritis achieving complete renal response (CRR) compared to proportion of patients achieving CRR from recent clinical trials. This protocol will additionally determine whether combination therapy using Belimumab (BEL) and Voclosporin (VCS) facilitates rapid discontinuation of MMF.

Conditions

Lupus Nephritis

Keywords

Lupus Nephritis; Voclosporin; Belimumab; MMF; MPA; Prednisone; Proteinura; SYNERGY

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure: Day 360 (12 Month) Outcome

  Proportion of Patients achieving and maintaining a Complete Clinical Renal Remission (CCRR) at 12 months. CCRR is defined as: UPCR≤ 0.5, eGFR≥60 and not \>20% below baseline, no rescue meds, sustained on repeat assessment 30 days later.

  12 months

Secondary Outcomes (4)

• Secondary Outcome Measure #1: Day 180 (6 Month) Outcome

  6 months

• Secondary Outcome Measure-#2:

  6 and 12 months

• Secondary Outcome Measure-#3:

  12 months

• Secondary Outcome Measure-#4:

  12 months

Study Arms (2)

EARLY MMF TERMINATION (90 days) ARM

ACTIVE COMPARATOR

EARLY MMF TERMINATION (90 days) ARM in which subjects are randomized 1:1

Drug: Voclosporin

EXTENDED MMF (360 days) ARM

ACTIVE COMPARATOR

EXTENDED MMF TERMINATION (360 days) ARM in which subjects are randomized 1:1

Drug: Voclosporin

Interventions

Voclosporin DRUG

The trial is an open label, parallel, randomized study with patients randomized 1:1 the EARLY MMF TERMINATION (90 days) ARM or the EXTENDED MMF (360 days) ARM looking at the addition of Voclosporin in patients with Lupus Nephritis taking Belimumab, MMF, and Prednisone.

EARLY MMF TERMINATION (90 days) ARM; EXTENDED MMF (360 days) ARM

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age 18-80 years at time of signing Informed Consent Form
• Ability to comply with the study protocol, in the investigator's judgment
• A diagnosis of SLE by any one of the following criteria: European League Against Rheumatism/ American College of Rheumatology/Systemic Lupus International Collaborating Clinics (EULAR/ACR/SLICC)
• At least one positive ANA defined as a \>1:80 titer or a positive anti-ds-DNA within the last 3 years will be accepted.
• ISN/RPS 2003 Class III, Class IV, Class III/V or Class IV/V Lupus Nephritis diagnosed and meet one of these criteria:
• i) A new diagnosis of LN (kidney biopsy current by SOC), or ii) A previous diagnosis of LN that has been treated, responded, but has flared (If diagnostic biopsy was \>24 months before SCREENING, a SOC repeat biopsy will be required for trial entry or by Medical Monitor approval if the last biopsy was less than 36 months prior to screening), or iii) A current diagnosis of LN confirmed by SOC kidney biopsy within the last 24 months prior to screening, or by Medical Monitor approval if the last biopsy - was less than 36 months prior to screening, who has been treated with MMF + glucocorticoids
• UPCR must be \>750 mg/gm from a 24 hour urine collection during screening. If the UPCR does not exceed 750 mg/gm, it may be repeated once during the screening period.
• Resting systolic blood pressure \<150 mm Hg and resting diastolic blood pressure \<90 mm Hg.
• Note: If the blood pressure is \>150/90 at screening it can be repeated twice in the screening period and if it is \<150/90 upon repeat the subject is eligible for study enrollment.
• Subject must be on maximum tolerated ACEi or ARB therapy as adjudicated by the site PI for ≥4 weeks prior to randomization.
• Note: Patients with confirmed ACEi or ARB intolerance defined as persistent cough, anaphylaxis, or angioedema will be eligible and treatment with another protein-lowering anti-hypertensive encouraged (See #9).
• Use of other protein-lowering agents, including non-dihydropyridine calcium channel blockers, sodium-glucose transporter 2 (SGLT2) inhibitors, mineralocorticoid receptor antagonists (MRA), will be allowed provided dosing has been stable for ≥4 weeks prior to randomization.
• Note: Titration of the above antihypertensive agents will NOT be allowed following randomization without Sponsor approval. Control for changes in blood pressure will be accomplished using non-protein lowering agents (e.g. Amlodipine, Nifedipine, or Hydralazine).
• EGFR \>30 ml/min/1,73m2 will be required for kidney biopsies obtained \>3.0 months from the start of drug administration.

You may not qualify if:

• \. Currently on renal replacement therapy (dialysis or a kidney transplant), has had dialysis within 3 months of screening or is expected to require renal replacement therapy within 6 months of screening 2. Received cyclophosphamide within 12 weeks of study drug administration 3. Has received treatment with any of the following prior to screening:
• a) Rituximab or Obinutuzumab within 24 weeks of screening and there is no measure of circulating C19 B cells. If the measure of circulating C19 B cells is over 10%, the subject will be eligible for study participation.
• b) Use of Atacicept, BION-1301, Sibeprenlimab, Povetacicept, or other agents, with the exception of Belimumab, that directly inhibit B call activating factor (BAFF) and/or a proliferation inducing ligand (APRIL) within 12 weeks of study screening.
• \. Use of High dose Human Immunoglobulin therapy, abatacept, adalimumab, infliximab, certolizumab, etanercept, golimumab, anakinra, canakinumab, tocilizumab, sarilumab, Satralizumab, Ustekinumab, and Anifrolumab within 12 weeks of study screening.
• \. Pure Class V LN on biopsy. 6. In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids).
• \. Any known hypersensitivity or contraindication to MMF, MPA, Cyclosporine, Tacrolimus, Voclosporin Corticosteroids, Belimumab or any components of these drug products.
• \. Current or medical history of:
• Pancreatitis or gastrointestinal hemorrhage within 6 months prior to screening.
• Active unhealed peptic ulcer within 3 months prior to screening. If an ulcer has healed and the subject is on adequate therapy, the subject may be randomized. 9. Positive human immunodeficiency virus (HIV) infection. 10. In the opinion of the Investigator, clinically significant drug or alcohol abuse 2 years prior to screening.
• \. Known malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas of the skin Note: Subjects with cervical dysplasia that is CIN1, but have been treated with conization or LEEP, and have had a normal repeat PAP are allowed.
• : Lymphoproliferative disease or previous total lymphoid irradiation. 13. Known viral infection (such as HBV and HCV) within 3 months of screening. If HBC and HCV status is unknown, testing should be performed during screening. Subjects with past medical history of HBC or HCV exposure with positive antibodies may be enrolled if a DNA PCR test was negative.
• \. Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid. QuantiFERON gold test must be negative at screening or subject taking isoniazid. Note: If positive at screening the subject can be screen failed, treated, and rescreened in 4 weeks with a confirmed negative chest x-ray.
• \. Patients with known "poor intravenous access" WILL be allowed to participate having placement of a "passport",or port, central IV access or its equivalent for subjects requiring IV infusions of Belimumab upon review and approval by the Medical Monitor 16. Other known clinically significant active medical conditions, such as:
• a) Severe cardiovascular disease, including congestive heart failure b) history of cardiac dysrhythmia or congenital long QT syndrome. QTcF (QT interval duration corrected for heart rate using method of Fridericia) exceeding 480 msec in the presence of a normal QRS interval (\<110 msec) on historic ECG, if available. An ECG is not is not required for study entry.
• \. Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than 2.5 times the upper limit of normal) at screening.

Sponsors & Collaborators

• NephroNet, Inc.: lead

Study Sites (7)

AARA Clinical Research

Glendale, Arizona, 85306, United States

RECRUITING

Piedmont Physicians Rheumatology

Atlanta, Georgia, 30318, United States

RECRUITING

Georgia Nephrology Research Institute

Lawrenceville, Georgia, 30046, United States

RECRUITING

Parris & Associates

Lawrenceville, Georgia, 30046, United States

RECRUITING

Nephrology Clinical Trials Unit The Ohio State University Wexner Medical Center

Columbus, Ohio, 43201, United States

RECRUITING

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

AARA Clinical Research

Fort Worth, Texas, 76109, United States

RECRUITING

MeSH Terms

Conditions

Lupus Nephritis

Interventions

voclosporin

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• James Tumlin, MD

  NephroNet, Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeremy Whitson

CONTACT

423-943-4265; jwhitson@nephronet.com

Julie Scoggin

CONTACT

804-467-3158; jscoggin@nephronet.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The trial has 2 interventional arms. One treatment regimen is provided to study subjects.

Study Record Dates

• First Submitted: September 26, 2025
• First Posted: November 6, 2025
• Study Start: October 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: November 6, 2025

Record last verified: 2025-11

Locations

US (7)