Voclosporin for Lupus Nephritis

(VOCAL-EXT Trial)

Enrolling by invitation at 6 trial locations

Overseen By Ernie Yap

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Aurinia Pharmaceuticals Inc.

Must be taking: MMF

Must not be taking: Cholestyramine, CNIs, CYP3A4/5 drugs

Disqualifiers: Renal dialysis, Kidney transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests voclosporin, a medication designed to help people with lupus nephritis, a kidney problem caused by lupus. The study examines the drug's safety and tolerability over an extended period. Participants must have completed a previous trial involving voclosporin and still require ongoing treatment for their condition. This trial may suit those who have lupus nephritis and have completed earlier treatment with this medication. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, like cholestyramine, calcineurin inhibitors (such as cyclosporin and tacrolimus), and strong CYP3A4/5 inhibitors and inducers (like ketoconazole and rifampin), as they are not allowed during the study. However, you will need to continue taking oral MMF (mycophenolate mofetil) for the duration of the study.

Is there any evidence suggesting that voclosporin is likely to be safe for humans?

Research shows that voclosporin is generally well-tolerated by people with lupus nephritis. In previous studies, about 86% of patients completed their treatment without unexpected safety issues. However, common side effects included infections, which occurred in both the voclosporin group and a comparison group.

Voclosporin carries a warning about the risk of serious infections and potential cancer, which are rare but serious concerns. Despite these risks, many patients respond well to the treatment, even if other medications have not worked for them. Overall, voclosporin appears to be a promising and safe option for managing lupus nephritis, but discussing any concerns with a healthcare provider is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Voclosporin is unique because it offers a new approach to treating lupus nephritis by targeting the immune system differently than traditional therapies. While most current treatments, like corticosteroids and cyclophosphamide, broadly suppress the immune system, voclosporin is a calcineurin inhibitor that more specifically modulates immune cell activity, potentially reducing inflammation in the kidneys with fewer side effects. Researchers are excited about voclosporin because it could provide a more precise treatment option, improving kidney outcomes and quality of life for patients with lupus nephritis.

What evidence suggests that voclosporin might be an effective treatment for lupus nephritis?

Research has shown that voclosporin effectively treats lupus nephritis, a kidney inflammation caused by lupus. In earlier studies, patients taking voclosporin experienced a significant decrease in proteinuria, indicating improved kidney health. More than half of these patients achieved complete kidney recovery, with much better kidney function. Another study found that after six months, patients using voclosporin had better kidney health than those on a placebo. These findings suggest that voclosporin can help manage lupus nephritis by improving kidney function. Participants in this trial will receive open-label voclosporin to further evaluate its effectiveness. ^{4 5 6 7 8}

Who Is on the Research Team?

Aurinia Study Director

Principal Investigator

Aurinia Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

This trial is for adolescents with active lupus nephritis who have completed a previous voclosporin study and need ongoing immunosuppressive therapy. They must be willing to take oral MMF throughout the study and not require dialysis or a kidney transplant during the trial.

Inclusion Criteria

I am willing to take oral MMF for the study duration.

Written informed consent from parent/guardian before any study-specific procedures are performed, if applicable per local regulations

I have given my consent to participate in this study.

Exclusion Criteria

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

I am on or expected to need kidney dialysis during the study.

I am not taking drugs that affect MMF absorption or strong CYP3A4/5 inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label voclosporin in addition to background standard of care with MMF and oral steroids for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Continuation of voclosporin treatment for long-term safety and efficacy assessment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Voclosporin

Trial Overview The trial tests the long-term safety of voclosporin in treating lupus nephritis over an additional 12 months, following up on earlier treatment from the VOCAL study. Participants will continue their current medication regimen alongside voclosporin.

How Is the Trial Designed?

Group I: Open Label Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Aurinia Pharmaceuticals Inc.

Lead Sponsor

Trials

18

Recruited

3,700+

Labcorp Corporation of America Holdings, Inc

Industry Sponsor

Trials

22

Recruited

3,600+

Published Research Related to This Trial

Voclosporin, when combined with mycophenolate mofetil and glucocorticoids, significantly improved complete renal response in lupus nephritis patients, with 43.7% achieving this outcome compared to 23.3% in the control group, based on an integrated analysis of 534 patients from two clinical trials.

The safety profile of voclosporin was comparable to the control, with similar rates of adverse events, most of which were mild to moderate, indicating that voclosporin is a safe and effective treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the Efficacy and Safety Profile of Voclosporin: An Integrated Analysis of Clinical Trials in Lupus Nephritis. Arriens, C., Teng, YKO., Ginzler, EM., et al.[2023]

In a small study of four patients with lupus nephritis, the combination of voclosporin and belimumab showed promising results, allowing for a reduction in glucocorticoid use and decreased proteinuria.

None of the patients experienced serious infections during the treatment, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Using Both Voclosporin and Belimumab in Four Patients With Lupus Nephritis. Baum, R., Geetha, D., Fatola, A., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37466424/

Safety and Efficacy of Long-Term Voclosporin Treatment ... Improved proteinuria persisted across three years of treatment, leading to more frequent complete renal responses in patients treated with voclosporin (50.9% vs ...

2. acrjournals.onlinelibrary.wiley.com acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42657

Safety and Efficacy of Long‐Term Voclosporin Treatment for ... Improved proteinuria persisted across three years of treatment, leading to more frequent complete renal responses in patients treated with ...

3. jrheum.org jrheum.org/content/52/Suppl_1/157

voclosporin was effective and safe in treating lupus ... Voclosporin in combination with MMF was effective in reducing proteinuria and preserving renal function in LN patients, even in those who have failed prior ...

4. thelancet.com thelancet.com/article/S0140-6736(21)00578-X/fulltext

Efficacy and safety of voclosporin versus placebo for lupus ... There was a significant increase in 6-month complete renal response rates for the voclosporin group dosed 23·7 mg twice daily compared with placebo. The 23·7 mg ...

5. journals.lww.com journals.lww.com/cjasn/fulltext/2024/03000/efficacy_of_voclosporin_in_proliferative_lupus.9.aspx

Efficacy of Voclosporin in Proliferative Lupus Nephritis wit... Compared with the control arm (10%), a greater proportion of patients treated with voclosporin achieved a complete renal response at 6 months (20%, OR, 2.18; 95 ...

6. lupkynispro.com lupkynispro.com/safety/

Safety | LUPKYNIS® (voclosporin) Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12128604/

Post-marketing safety surveillance of voclosporin Moreover, voclosporin has a black box warning for potential malignancies and serious infections risk, which may be fatal. Therefore, there is a ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2021/213716Orig1s000RiskR.pdf

center for drug evaluation and research - accessdata.fda.gov In the pooled lupus nephritis population, there were 27 adverse events of infections/infestations in both the voclosporin treated group and the ...