Voclosporin in Adolescents With Lupus Nephritis

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of voclosporin compared to placebo in achieving renal response following 24 weeks of therapy in adolescents with active lupus nephritis (LN).

Detailed Description
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This is a 24 week, dose escalation study of voclosporin in addition to standard of care with mycophenolate mofetil (MMF) and steroids, consisting of 3 treatment periods, in which period 1 is double-blind, placebo controlled, and period 2 and period 3 are open-label, with increasing doses of voclosporin in a pediatric population.

Official Title
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A Double-Blind, Placebo-Controlled, Dose Escalation Study to Assess the Efficacy, Safety and Pharmacokinetics of Voclosporin in Adolescents With Lupus Nephritis

Conditions
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Adolescent Lupus Nephritis

Intervention / Treatment
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* Drug: Voclosporin
* Drug: Placebo Oral Capsule


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Previous diagnosis of systemic lupus erythematosus (SLE) as per the 2019 EULAR/ ACR classification criteria. Subjects with kidney biopsy confirmed active lupus nephritis. Exclusion Criteria: Estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 at screening. Current or medical history of: Congenital or acquired immunodeficiency. Clinically significant drug or alcohol abuse prior to screening. Malignant neoplasm. Lymphoproliferative disease or previous total lymphoid irradiation. Known severe viral infections within 3 months of screening; or known human immunodeficiency virus infection, or hepatitis B or C virus infection at any time prior to screening. Active tuberculosis (TB) or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid. Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period. Other known clinically significant active medical conditions, for which the condition or the treatment of the condition may affect the study assessments or outcomes. Currently taking or known need for any of the following medications: Immunosuppression biologic agents within 12 weeks prior to randomization, cyclophosphamide, calcineurin inhibitors (CNIs) and live attenuated vaccines, initiation or dose change of ACE inhibitors/ARBs within 4 weeks prior to randomization, IV corticosteroids and IV immunoglobulin within 2 weeks prior to screening, strong CYP3A4/5 inhibitors and inducers within 2 weeks prior to randomization.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voclosporin treatment group 1<br>2 capsules (15.8 mg) BID of voclosporin | Drug: Voclosporin<br>* calcineurin inhibitor<br>|
| Placebo Comparator: Placebo treatment group<br>2 capsules BID of placebo | Drug: Placebo Oral Capsule<br>* matching placebo capsule<br>|
| Experimental: Voclosporin treatment group 3<br>3 capsules (23.7 mg) BID of voclosporin | Drug: Voclosporin<br>* calcineurin inhibitor<br>|
| Experimental: Voclosporin treatment group 4<br>Maximum dose of 4 capsules (31.6 mg) BID of voclosporin. | Drug: Voclosporin<br>* calcineurin inhibitor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with renal response | Renal response defined as UPCR ≤0.5 mg/mg, eGFR ≥60 mL/min/1.73 m2 or no decrease from baseline of >20%, no rescue medication and no steroid use >10 mg/day for ≥3 consecutive days or for ≥7 days in total between week 16 to 24 | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to UPCR of ≤0.5 mg/mg. | Time in days to reduction in UPCR to ≤ 0.5 mg/mg | Baseline to Week 24 | 
| Proportion of subjects with partial renal response | defined as ≥50% reduction from baseline in UPCR | Week 24 | 
| Time to 50% Reduction in UPCR | Time in days to reduction from baseline UPCR of at least 50% Organ Class, and preferred term. | Baseline to Week 24 | 
| Number of treatment-emergent adverse events (TEAEs) will be summarized by treatment group | Treatment-emergent adverse events will be summarized by treatment group, System Organ Class, and preferred term | Baseline to Week 24 | 

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