Anifrolumab for Lupus

Recruiting in Palo Alto (17 mi)

Overseen by Mariana J Kaplan, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

Background: People with systemic lupus erythematosus (SLE) are at risk of developing complications in their blood vessels. This can increase the risk of heart attacks or stroke. No medications have been effective at reducing this risk in people with lupus. Objective: To test whether a drug (anifrolumab) can improve blood vessel function and reduce blood vessel inflammation in people with SLE. Eligibility: People aged 18 to 80 years with SLE. Design: Participants will undergo screening. They will have a physical exam. They will have blood and urine tests. They will have a test of their heart function and a chest X-ray. They will answer questions about their SLE symptoms. Participants will visit the clinic 9 times in 8 months. After screening, visits will be 4 weeks apart. Each visit may take up to 4 hours. Participants will receive infusions from a tube attached to a needle inserted into a vein in the arm (IV). Some will receive anifrolumab. Others will receive a placebo treatment. They will not know which one they are getting. At some visits they will have additional tests: CAVI (cardio-ankle vascular index) tests blood vessel function. Participants will lie still for 20 minutes. Small electrodes will be placed on both wrists with stickers. A microphone will be placed on their chest. Blood pressure cuffs will be wrapped around their ankles and arms. FDG-PET/CT is an imaging procedure. Participants will receive a substance through an IV line. They will lie on a table for 110 minutes while a machine captures images of their body.

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.

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

Anifrolumab has been shown to be effective in treating systemic lupus erythematosus (SLE), a condition where the immune system attacks the body's own tissues, as it was approved in the USA for adults with moderate to severe SLE. Additionally, studies have demonstrated its safety and effectiveness in patients with lupus nephritis, a serious kidney inflammation caused by lupus. ^{1 2 3 4 5}

Is Anifrolumab safe for humans?

Anifrolumab has been studied for safety in people with systemic lupus erythematosus (SLE). In clinical trials, serious side effects were reported in 8-16% of patients taking Anifrolumab, compared to 16-19% of those taking a placebo. A higher rate of herpes zoster (shingles) was noted in those taking Anifrolumab (up to 7%) compared to placebo (up to 2%). ^{1 2 3 6 7}

What makes the drug Anifrolumab unique for treating lupus?

Anifrolumab is unique because it is a monoclonal antibody that specifically targets and blocks the type I interferon receptor, which plays a key role in the development of systemic lupus erythematosus (SLE). This mechanism of action is different from other lupus treatments, and it has shown effectiveness in reducing disease activity and the need for oral corticosteroids in clinical trials. ^{1 2 7 8 9}

Research Team

Mariana J Kaplan, M.D.

Principal Investigator

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

Eligibility Criteria

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 between 18 and 80 years old.

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

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

Trial Timeline

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

Treatment Details

Interventions

• Anifrolumab (Monoclonal Antibodies)
• 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.

Participant Groups

Group I: Patient Active Control 1 Intervention

anifrolumab

Group II: Patient placebo Placebo Group 1 Intervention

placebo

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

508

Recruited

1,090,000+

Dr. Lindsey A. Criswell

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

Director since 2021

MD, MPH, DSc

Dr. Robert Colbert

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

Clinical Director since 2014

MD

Findings from Research

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 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 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 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 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]

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]

References

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

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

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

Anifrolumab: First Approval. [2022]

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

Safety and efficacy of anifrolumab therapy in systemic lupus erythematosus in real-world clinical practice: LOOPS registry. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

5. 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]

6. United States 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. [2023]

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]

8. England 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. [2022]

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

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