Anifrolumab for Lupus Nephritis

(IRIS Trial)

Recruiting at 147 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must not be taking: Cyclophosphamide, MMF, Tacrolimus, others

Disqualifiers: HIV, Hepatitis, Cancer, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing an IV medication called anifrolumab in adults with severe lupus nephritis. The goal is to see if it can reduce inflammation and prevent kidney damage. All patients will also receive standard treatments. Anifrolumab is approved by the FDA for treating moderate to severe systemic lupus erythematosus (SLE).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does list certain medications that you should not have received recently. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug Anifrolumab for treating lupus nephritis?

Research shows that Anifrolumab, especially at higher doses, is effective in treating lupus nephritis, as it was ranked second in effectiveness for renal complete remission among several biologics. It was found to be more effective than a lower dose of Anifrolumab and placebo in clinical trials. ^{1 2 3 4 5}

Is anifrolumab safe for humans?

Anifrolumab has been studied for safety in people with lupus, showing a similar rate of serious side effects compared to a placebo, but with a higher chance of viral infections like shingles. Careful patient selection and precautions can help manage these risks. ^{3 4 5 6 7}

How is the drug Anifrolumab unique in treating lupus nephritis?

Anifrolumab is unique because it targets the type I interferon receptor, which plays a key role in the immune system's involvement in lupus nephritis. This mechanism is different from other treatments, making it a novel option for patients with this condition. ^{1 2 3 4 5}

Eligibility Criteria

Adults with active proliferative lupus nephritis, a kidney condition caused by systemic lupus erythematosus. Participants must have had a kidney biopsy within the last 6 months, show no signs of tuberculosis, and meet specific criteria for kidney function and protein levels in urine. Those with pure Class V lupus nephritis or severe infections like COVID-19 are excluded.

Inclusion Criteria

Your kidney function, as measured by a calculation called eGFR, is at least 35 mL/min/1.73 m2.

You meet the updated 2019 criteria for diagnosing systemic lupus erythematosus (SLE).

You had a kidney biopsy in the 6 months before joining the study or during the screening period.

Exclusion Criteria

I have only had skin cancer or early-stage cervical cancer, which were cured.

You have evidence of hepatitis C or have active hepatitis B.

I have had a severe case of COVID-19.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anifrolumab or placebo as added to SOC for up to 104 weeks

104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Anifrolumab (Monoclonal Antibodies)

Trial Overview The trial is testing Anifrolumab's effectiveness compared to a placebo in treating active proliferative lupus nephritis. Patients will receive IV infusions of either Anifrolumab or placebo to see if there's an improvement in their condition.

Participant Groups

Group I: Anifrolumab Experimental Treatment 1 Intervention

Solution for intravenous infusion

Group II: Placebo Placebo Group 1 Intervention

Solution for intravenous infusion

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In a phase II study involving 147 patients with active lupus nephritis, the primary endpoint of improved urine protein-creatinine ratio was not met for anifrolumab compared to placebo, indicating limited efficacy in this measure.

However, the intensified regimen of anifrolumab showed numerical improvements in secondary outcomes, such as complete renal response and sustained glucocorticoid reductions, although there was a higher incidence of herpes zoster in the anifrolumab groups compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Jayne, D., Rovin, B., Mysler, EF., et al.[2022]

In a meta-analysis of 10 clinical trials involving 2148 subjects, belimumab and obinutuzumab were found to be the most effective biologics for achieving complete remission in lupus nephritis, significantly outperforming placebo and other treatments.

The safety profile of these new biologics is generally good, with belimumab and obinutuzumab showing fewer serious adverse events compared to other treatments, indicating they are safe options for patients when combined with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of novel biologics in the treatment of lupus nephritis based on registered clinical trials: a systematic review and network meta-analysis. Li, F., Cui, W., Huang, G., et al.[2023]

In a 3-year study involving 218 patients with moderate-to-severe systemic lupus erythematosus (SLE), long-term treatment with anifrolumab showed an acceptable safety profile, with only 6.9% of patients discontinuing due to adverse events.

Patients experienced sustained improvements in SLE disease activity and health-related quality of life, with no new safety concerns identified, indicating that anifrolumab effectively manages SLE over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study. Chatham, WW., Furie, R., Saxena, A., et al.[2021]

Anifrolumab is a monoclonal antibody that targets the type 1 interferon receptor and has been approved in the USA for treating moderate to severe systemic lupus erythematosus (SLE) in adults, marking a significant advancement in autoimmune disorder therapies.

The drug is currently being evaluated in ongoing clinical studies and is under regulatory review in the EU and Japan, indicating its potential for broader use in managing SLE and related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab: First Approval. Deeks, ED.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and safety of novel biologics in the treatment of lupus nephritis based on registered clinical trials: a systematic review and network meta-analysis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Anifrolumab in Adults With Systemic Lupus Erythematosus: Results of a Phase II Open-Label Extension Study. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Anifrolumab: First Approval. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Anifrolumab, a monoclonal antibody to the type I interferon receptor subunit 1, for the treatment of systemic lupus erythematosus: an overview from clinical trials. [2021]