Anifrolumab for Lupus

Overseen By Mariana J Kaplan, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Must be taking: Prednisone

Must not be taking: Immunosuppressants, Biologics, IFN therapy, others

Disqualifiers: Recent surgery, Active severe SLE, others

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

Compensation: Varies

Number of Visits: 10

Duration: 8 months

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called anifrolumab (an immunotherapy) to determine if it can aid people with systemic lupus erythematosus (SLE) by improving blood vessel health and reducing inflammation. People with SLE face a higher risk of heart attacks and strokes, and current medications don't effectively lower this risk. Participants will receive either anifrolumab or a placebo through an IV without knowing which one they receive. Those diagnosed with SLE and experiencing complications affecting their daily lives might be suitable for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you keep taking your current lupus medications and any stable medications for diabetes, hypertension, and statins. You cannot change these medications during the trial.

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

In a previous study, researchers examined the safety of anifrolumab for people with systemic lupus erythematosus (SLE). The results showed that anifrolumab was generally well-tolerated, with most participants experiencing no major side effects. Another study found that long-term use of anifrolumab was safe for most patients.

The FDA has approved anifrolumab for treating certain lupus symptoms, suggesting it is considered safe for people. However, like any treatment, some individuals might experience mild side effects such as headaches or nausea. Studies indicate these side effects are neither common nor severe.

For those considering joining a trial, discussing potential risks and benefits with a doctor is always advisable. ^{1 2 3 4 5}

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

Anifrolumab is unique because it targets the type I interferon receptor, a pathway not directly addressed by most existing lupus treatments, which often include corticosteroids, antimalarials, and immunosuppressants. Researchers are excited about anifrolumab because it offers a more targeted approach, potentially reducing the immune system's overactivity without broadly suppressing it. This could mean fewer side effects and a more effective treatment for lupus patients who don't respond well to current therapies.

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

Research shows that anifrolumab holds promise for treating systemic lupus erythematosus (SLE). Studies have found that it significantly reduces disease activity and the need for medications like corticosteroids. It also lowers the risk of flares, which are sudden increases in symptoms. Anifrolumab has effectively improved joint and skin problems related to lupus. In this trial, some participants will receive anifrolumab to test its potential to improve blood vessel function and reduce inflammation in people with lupus, while others will receive a placebo for comparison. ^{2 3 6 7 8}

Who Is on the Research Team?

Mariana J Kaplan, M.D.

Principal Investigator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Are You a Good Fit for This Trial?

Adults aged 18-80 with Systemic Lupus Erythematosus (SLE) are eligible for this trial. They must be in good health or have stable lupus, on consistent medication for at least 4 weeks, and not planning to change their meds during the trial. Participants need a history of vaccination against COVID-19 and Varicella Zoster, use effective contraception if applicable, and cannot have had recent severe cardiovascular events or other serious health conditions.

Inclusion Criteria

I am generally healthy or have been diagnosed with lupus according to specific criteria.

For females and males of reproductive potential: use of highly effective contraception from screening and agreement to use such a method during study participation and for an additional 16 weeks after the end of study medication administration. For the purpose of this study abstinence will be considered as an effective form of contraception

I am vaccinated against COVID-19 and Varicella Zoster or have antibodies.

Exclusion Criteria

Concurrent enrollment in another clinical study with an investigational product

Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results

Receipt of any of the following: Azathioprine >200 mg/day, Mycophenolate mofetil > 3 g/day or mycophenolic acid >2.16 g/day, Oral, SC, or intramuscular methotrexate >25 mg/week, Mizoribine >150 mg/day, Leflunomide more than 20 mg and any other immunosuppressant usage at the discretion of the PI, Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to week 0 (day 1), whichever is greater, Prior receipt of anifrolumab, Receipt of any commercially available biologic agent within 5 half-lives prior to signing of the ICF, Receipt of B cell depleting therapy (including but not limited to belimumab, ocrelizumab, ofatumumab, atacicept, Obinutuzumab, or rituximab), <26 weeks prior to the signing of the consent for all B-cell depleting therapy or <40 weeks prior to the signing of the ICF for atacicept, Receipt of any of the following: (a) Intra-articular, intramuscular or IV corticosteroids within 4 weeks prior to Day 1 (b) Any live or attenuated vaccine within 8 weeks prior to signing the ICF (administration of killed vaccines is acceptable), Receipt of the following medications during the study period will lead to immediate discontinuation of investigational product: Cyclophosphamide, IFN therapy (alpha 2a and 2b, beta 1a and 1b, and pegylated IFNs alpha 2a and 2b), Investigational agents, Biologic immunomodulators (including, but not limited to, belimumab, abatacept, or rituximab), Live or attenuated vaccines, Plasmapheresis, BCG vaccine, Any immunoglobulin (Ig) therapy, Intravenous corticosteroids >1 gm methylprednisolone or equivalent, History or evidence of suicidal ideation within the past 6 months; or any suicidal behavior within the past 12 months based on screening or at baseline, Recent cardiac or stroke event (with in the last year prior to week 0 (day 1)), Active SLE disease with SLEDAI 2K >6, Active severe or unstable neuropsychiatric SLE including, but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex: That would make the subject unable to fully understand the ICF OR Where, in the opinion of the Principal Investigator (PI), protocol specified SOC is insufficient and utilization of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated, Active severe SLE-driven renal disease where, in the opinion of the PI, protocol specified standard of care (SOC) is insufficient and utilization of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated, History of or current diagnosis of catastrophic or severe anti-phospholipid syndrome within 1 year prior to signing the ICF. Antiphospholipid syndrome adequately controlled by anticoagulant therapy for at least 3 months is acceptable, Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation, Confirmed positive test for hepatitis B serology for: Hepatitis B surface antigen (HBsAg), OR Hepatitis B core antibody (HBcAb). If positive for HBcAb we will check hepatitis B virus (HBV) DNA. If HBV DNA is detected above the lower limit of quantitation (LLOQ) by at screening subject will be excluded, Note: Subjects who are only HBcAb positive at screening will be tested every month for HBV DNA. To remain eligible for the study, the subject s HBV DNA levels must remain below the LLOQ as per the central laboratory, Positive test for hepatitis C antibody along with detectable Hepatitis C viral RNA, Any severe herpes infection at any time prior to Week 0 (Day 1), including, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes (ever), Any herpes zoster, cytomegalovirus (CMV) or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF, Any of the following: Clinically significant chronic infection (i.e., osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to week 0 (day1) (chronic nail infections are allowed), Any infection requiring hospitalization or treatment with IV antibiotics not completed at least 4 weeks prior to week 0 (day1), Any infection requiring oral antimicrobials (including antivirals) within 2 weeks prior to Day 1, except if taking antivirals/antimicrobials prophylactically, History of cancer, apart from: Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy >=3 months prior to Week 0 (Day 1), Cervical cancer in situ treated with apparent success with curative therapy (Bullet)1 year prior to Week 0 (Day 1), Pregnancy or lactation or intend to become pregnant anytime from initiation of Screening until completion of study, Spontaneous or induced abortion, still or live birth, or pregnancy 4 weeks prior to week 0 (day1), Known allergic reactions to any component of the investigational product formulation or history of anaphylaxis to any human gamma globulin therapy, Tested positive for COVID-19 infection on the day of screening or up to 21 days prior to screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive infusions of either anifrolumab or placebo every 4 weeks for 8 months

8 months

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anifrolumab
• Placebo

Trial Overview The study is testing anifrolumab's effectiveness in improving blood vessel function and reducing inflammation compared to a placebo. Participants will receive infusions without knowing which treatment they get. The study involves nine clinic visits over eight months with tests like CAVI for blood vessel function and FDG-PET/CT scans for imaging body inflammation.

How Is the Trial Designed?

Group I: Patient Active Control 1 Intervention

anifrolumab

Group II: Patient placebo Placebo Group 1 Intervention

placebo

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?

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Lead Sponsor

Trials

508

Recruited

1,090,000+

Published Research Related to This Trial

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]

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]

Anifrolumab demonstrated a high retention rate of 89.7% at 26 weeks in patients with systemic lupus erythematosus (SLE), indicating its potential as a long-term treatment option.

In patients experiencing minor flares, anifrolumab significantly reduced glucocorticoid (GC) doses and disease activity (measured by the SELENA-SLEDAI score) compared to standard care, suggesting it may effectively manage SLE without increasing GC use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry. Miyazaki, Y., Funada, M., Nakayamada, S., et al.[2023]

In a long-term extension study involving patients with systemic lupus erythematosus (SLE), anifrolumab 300 mg showed a favorable safety profile, with lower rates of serious adverse events (SAEs) compared to placebo (8.5 vs 11.2 per 100 patient-years).

Anifrolumab also led to greater improvements in disease activity and reduced glucocorticoid use compared to placebo, supporting its efficacy and favorable benefit-risk profile for treating moderate-to-severe SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Kalunian, KC., Furie, R., Morand, EF., et al.[2023]

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]

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]

In a post hoc analysis of a phase IIb trial involving patients with moderate to severe systemic lupus erythematosus (SLE), anifrolumab 300 mg every 4 weeks significantly improved rash and arthritis symptoms compared to placebo, with notable improvements in various assessment scales.

The treatment was particularly effective in patients with a high type I interferon gene signature, showing substantial resolution of rash and improvement in arthritis, while results in patients with a low gene signature were less pronounced, indicating a need for further research in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab effects on rash and arthritis: impact of the type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus erythematosus. Merrill, JT., Furie, R., Werth, VP., et al.[2022]

In a phase IIb trial involving 305 patients with moderate-to-severe systemic lupus erythematosus (SLE), anifrolumab significantly improved disease activity compared to placebo, particularly in patients with a high interferon gene signature, with 34.3% of patients on the 300 mg dose achieving a response at week 24.

Anifrolumab's safety profile was generally similar to placebo, but it was associated with a higher incidence of herpes zoster and influenza-like symptoms, indicating a need for monitoring these potential side effects in treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon Inhibition for Lupus with Anifrolumab: Critical Appraisal of the Evidence Leading to FDA Approval. Loncharich, MF., Anderson, CW.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39104974/

Evaluation of the Efficacy and Safety of Anifrolumab in ... Anifrolumab shows great promise as a treatment for moderate-to-severe SLE, providing significant efficacy together with a manageable safety profile.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1912196

Trial of Anifrolumab in Active Systemic Lupus Erythematosus Monthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did ...

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

Clinical Data - SAPHNELO For HCPs Learn about the efficacy and clinical study results of SAPHNELO® (anifrolumab-fnia) intravenous injection in patients with moderate-to-severe SLE who are ...

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. lupus.bmj.com lupus.bmj.com/content/12/1/e001486

Characteristics and clinical outcomes of patients with ... In clinical trials, anifrolumab showed benefits in reducing oral corticosteroid use, flare incidence and achievement of prolonged and sustained ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36211347/

Evaluation of anifrolumab safety in systemic lupus ... Anifrolumab is a new strategy for the treatment of systemic lupus erythematosus. It could antagonize the activity of all type 1 interferons.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01438489

NCT01438489 | A Study of the Efficacy and Safety of MEDI- ... The purpose of this study is to evaluate the efficacy and safety of MEDI-546 compared to placebo in subjects with chronic, moderately-to-severely active ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8252065/

Long‐Term Safety and Efficacy of Anifrolumab in Adults ... Long‐term anifrolumab treatment demonstrates an acceptable safety profile with sustained improvement in SLE disease activity, HRQoL, and serologic measures.