Anifrolumab for Lupus Nephritis

(IRIS Trial)

Recruiting at 173 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

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

Disqualifiers: HIV, Hepatitis, Cancer, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of anifrolumab for individuals with active proliferative lupus nephritis. Lupus nephritis is a kidney issue caused by lupus, an autoimmune disease where the immune system attacks the body's own tissues. Participants will receive either anifrolumab (an immunotherapy drug) or a placebo through an IV to evaluate its efficacy. Suitable candidates have active proliferative lupus nephritis, confirmed by a recent kidney biopsy, and protein in their urine. As a Phase 3 trial, this study is the final step before FDA approval, offering participants the opportunity to help potentially bring a new treatment to market.

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.

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

Research has shown that anifrolumab has been tested for safety in people with systemic lupus erythematosus (SLE), which relates to lupus nephritis. Some individuals experienced serious infections while using anifrolumab, as it can weaken the immune system's ability to fight infections. This is crucial to consider if infections occur frequently.

In addition to infections, other side effects exist, but doctors monitor these closely. Since anifrolumab has approval for other types of lupus, there is some confidence in its safety. However, always consult your doctor to determine if this treatment suits your needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus nephritis?

Anifrolumab is unique because it targets the type I interferon receptor, which plays a key role in the inflammation process associated with lupus nephritis. Unlike the standard treatments, which often include corticosteroids and immunosuppressants like mycophenolate mofetil, anifrolumab specifically blocks the signaling pathway of certain proteins that drive the disease's symptoms. This targeted approach not only offers a new mechanism of action but also holds promise for reducing side effects and improving quality of life for patients. Researchers are excited about this treatment because it represents a potential breakthrough in managing lupus nephritis with greater precision and fewer side effects.

What evidence suggests that Anifrolumab might be an effective treatment for Lupus Nephritis?

Research has shown that anifrolumab, which participants in this trial may receive, may help treat lupus nephritis, a kidney problem related to lupus. In earlier studies, patients who took anifrolumab showed better kidney function, as indicated by improvements in the estimated glomerular filtration rate, compared to those who took a placebo. Anifrolumab has also effectively reduced symptoms in other lupus-related issues, particularly those affecting the skin and joints. These findings suggest that anifrolumab might help manage lupus nephritis by reducing inflammation and symptoms. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Anifrolumab

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.

How Is the Trial Designed?

Group I: Anifrolumab Experimental Treatment 1 Intervention

Solution for intravenous infusion

Group II: Placebo Placebo Group 1 Intervention

Solution for intravenous infusion

Anifrolumab is already approved in United States, European Union for the following indications:

Approved in United States as Saphnelo for:

• Moderate to severe systemic lupus erythematosus (SLE)

Approved in European Union as Saphnelo for:

• Moderate to severe systemic lupus erythematosus (SLE)

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

Published Research Related to This Trial

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 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]

Belimumab and anifrolumab are two targeted biological drugs approved for treating systemic lupus erythematosus (SLE), with belimumab primarily affecting adaptive immune responses and anifrolumab potentially causing organ-specific effects due to its action on the IFNAR1 receptor.

Safety data indicate that anifrolumab may increase the risk of certain viral infections, while belimumab appears to have a more favorable safety profile, suggesting that careful patient selection and monitoring are essential to optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment. Kirou, KA., Dall Era, M., Aranow, C., et al.[2022]

In the TULIP-LN trial involving 147 patients with active lupus nephritis, the intensified regimen of anifrolumab (900 mg followed by 300 mg) showed a higher rate of complete renal response at Week 104 compared to the basic regimen and placebo (27.3% vs 18.6% and 17.8%).

The safety profile of anifrolumab remained consistent over two years, with 72% of patients reporting at least one adverse event, but serious adverse events were relatively low, suggesting that anifrolumab is a tolerable treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. Jayne, D., Rovin, B., Mysler, E., 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]

Anifrolumab, a monoclonal antibody targeting the type I interferon receptor, has shown significant efficacy in treating moderately to severely active systemic lupus erythematosus (SLE), with over 16% improvement compared to placebo in response rates after 52 weeks in phase 3 studies (TULIP-1 and TULIP-2).

The safety profile of anifrolumab is comparable to placebo, although there is a higher incidence of herpes zoster in patients receiving the treatment (up to 7% vs. 2% for placebo), indicating that while effective, monitoring for this specific side effect is important.

NCBI (Pubmed)

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. Tanaka, Y., Tummala, R.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37607780/

Anifrolumab in lupus nephritis: results from second-year ... The improvements in estimated glomerular filtration rate were numerically larger in both anifrolumab groups versus placebo. Conclusions: The safety and ...

2. saphnelohcp.com saphnelohcp.com/clinical-data.html

Clinical Data - SAPHNELO For HCPs The reduction in disease activity seen in BICLA and SRI-4 was related primarily to improvement in the mucocutaneous and musculoskeletal organ systems.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05138133

NCT05138133 | Phase 3 Study of Anifrolumab in Adult ... The purpose of this study is to evaluate the efficacy and safety of IV antifrolumab in adult patients with Active Proliferative Lupus Nephritis.

4. jrheum.org jrheum.org/content/52/Suppl_1/254

REAL-WORLD EFFICACY AND SAFETY DATA OF ... ANI showed promising results, reducing overall and organ-specific disease activity, confirming its efficacy in cutaneous and joint manifestations.

5. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/SAPHNELO-self-administration-TULIP-SC-Phase-III-trial-meets-primary-endpoint-in-patients-with-systemic-lupus-erythematosus-based-on-an-interim-analysis.html

SAPHNELO self-administration TULIP-SC Phase III trial ... Subcutaneous administration of first-in-class biologic SAPHNELO demonstrates statistically significant and clinically meaningful reduction ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12278508/

Post-marketing safety signals of anifrolumab in systemic ... This study provides valuable safety data on the real-world application of anifrolumab, confirming known AEs and revealing additional potential risks.

7. saphnelo.com saphnelo.com/safety

Safety | SAPHNELO® (anifrolumab-fnia) Injection for ... SAPHNELO may cause serious side effects, including: Serious infections: SAPHNELO can lower the ability of your immune system to fight infections.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761123s000lbl.pdf

SAPHNELO (anifrolumab-fnia) injection, for intravenous use Serious Infections: Serious and sometimes fatal infections have occurred in patients receiving SAPHNELO. SAPHNELO increases the.