Long-Term Voclosporin Treatment in Adolescent Subjects With Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to assess the long-term safety and tolerability of voclosporin for up to an additional 12 months following completion of treatment in the AUR-VCS-2020-03 study (VOCAL) in adolescents with active lupus nephritis.

Detailed Description
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This is a 12 month, prospective, multi-center, long-term, open-label extension study of voclosporin in addition to background standard of care with mycophenolate mofetil (MMF) and oral steroids. Subjects completing participation and treatment with study drug (voclosporin/placebo) of the VOCAL Study (AUR-VCS-2020-03 ; NCT05288855) and meeting all eligibility criteria will continue to receive open-label treatment with voclosporin for approximately 12 months giving a total study treatment duration of 18 months from the start of VOCAL. Subjects completing treatment in Group 2 of the VOCAL study who were receiving placebo will switch to receive open-label voclosporin initially at the same number of capsules as was being administered at the End of Study (EOS) Visit in VOCAL. All subjects will continue to receive background therapy of MMF and oral corticosteroids starting at the same dose as at completion of the VOCAL study. When clinically indicated, subjects are permitted to be titrated off oral corticosteroids.

Official Title
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An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of Voclosporin in Adolescent Subjects With Lupus Nephritis

Conditions
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Adolescent Lupus Nephritis

Intervention / Treatment
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* Drug: voclosporin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent from parent/guardian before any study-specific procedures are performed, if applicable per local regulations. Age-appropriate assent or informed consent from subject before any study-specific procedures are performed. Subjects who have completed 24 weeks of treatment with study drug (voclosporin/placebo) in the VOCAL study. Subjects who had a temporary interruption and were able to successfully re-start study drug will be allowed to enroll after Medical Monitor approval. In the opinion of the Investigator subject requires continued immunosuppressive therapy. Subject is willing to continue to take oral MMF for the duration of the study. Exclusion Criteria: Currently taking or known need for any of the following medications during the study: Cholestyramine or other drugs that may interfere with enterohepatic recirculation of MMF Calcineurin inhibitors (CNIs) (e.g., cyclosporin and tacrolimus) Strong CYP3A4/5 inhibitors and inducers (e.g., ketoconazole, rifampin, itraconazole, clarithromycin) Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. A planned kidney transplant within study treatment period. Subjects with any medical condition which in the Investigator's judgement may be associated with increased risk to the subject or may interfere with study assessments or outcomes

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label<br>All subjects will receive open label voclosporin initially at the same number of capsules as assigned at Week 24 (End of Study Visit) in AUR-VCS-2020-03 (VOCAL ; NCT05288855). At the Investigator's discretion and after consultation with the Medical Monitor, dose titration up or down in the study will be permitted up to the maximum dose that was studied in AUR-VCS-2020-03. | Drug: voclosporin<br>* Subjects will receive 2 capsules (15.8 mg) BID (twice daily), 3 capsules (23.7 mg) BID or 4 capsules (31.6 mg) BID of voclosporin in addition to standard of care with mycophenolate mofetil (MMF) and steroids.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment Emergent Adverse Events (TEAE) | Incidence (subject counts and event counts) of TEAEs summarized by System Organ Class and Preferred Terms using MedDRA | Per protocol from VOCAL-EXT Study Start to Study Completion plus a 30-day follow-up period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Response | Proportion of subjects with renal response at Month 12 and 18, defined based on the following parameters: urine protein creatinine ratio (UPCR) of ≤0.5 mg/mg, and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20%, and Received no rescue medication for lupus nephritis, and Did not receive >10 mg/day prednisone for ≥3 consecutive days or for ≥7 days in total prior to the renal response assessment | Per protocol from Study Start to Study Completion plus a 30-day follow-up period | 
| Urine Protein Creatinine Ratio (UPCR) | Proportion of subjects with UPCR of ≤0.7 mg/mg | Month 12 (VOCAL Study Completion/VOCAL-EXT Study Start) and Month 18 (VOCAL-EXT Study Completion) | 
| Partial Renal Response | Proportion of subjects in partial renal response as defined by ≥50% reduction from VOCAL baseline in UPCR | Month 12 (VOCAL Study Completion/VOCAL-EXT Study Start) and Month 18 (VOCAL-EXT Study Completion) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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voclosporin, lupus nephritis, calcineurin inhibitors, adolescents