Nature of Anifrolumab Impact on Vaccine-Emergent Immunity in SLE

NCT04726553 | Unknown Early Phase 1 FDA Drug

• 2 other identifiers: D3461C00023IRB 20-27
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 5

Brief Summary

This study to examines the impact of anifrolumab on disease activity, immune phenotypes, and development of neutralizing antibodies to quadrivalent influenza vaccine in patients with Systemic Lupus Erythematosus (SLE). 10 patients with moderately to severely active SLE will be treated with anifrolumab in addition to standard of care lupus treatments and 10 will receive only standard of care medications. All will receive influenza vaccine.

Conditions

Systemic Lupus Erythematosus (SLE)

Outcome Measures

Primary Outcomes (1)

• Change in immune response to quadrivalent flu vaccine

  Combined endpoint incorporating percentile ranks of log10 transformed ratios of antibody concentration and results of a hemagglutination inhibition assay.

  6 weeks after vaccination (8 weeks after baseline)

Secondary Outcomes (2)

• Proportion of patients who develop changes in autoantibodies after immunization with quadrivalent flu vaccine

  6 weeks after vaccination (8 weeks after baseline)

• Proportion of patients who develop flares after immunization with quadrivalent flu vaccine

  6 weeks after vaccination (8 weeks after baseline)

Study Arms (2)

Anifrolumab plus Standard of Care

EXPERIMENTAL

Anifrolumab will be added to Standard of Care Treatments for SLE

Drug: Anifrolumab

Standard of Care

PLACEBO COMPARATOR

Standard of Care Treatments for SLE

Drug: Standard of Care

Interventions

Anifrolumab DRUG

Anifrolumab is a monoclonal antibody which inhibits the Interferon alpha beta receptor (IFNAR) which is the main transducer of signals from Type I interferons.

Also known as: Medi 546

Anifrolumab plus Standard of Care

Standard of Care DRUG

Standard of Care treatments for Systemic Lupus Erythematosus

Also known as: azathioprine, methotrexate, mycophenolate mofetil, corticosteroids, antimalarials

Standard of Care

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Female and/or male aged 18 to 70 years inclusive.
• Meet the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus.
• Have moderate to severely active signs or symptoms defined as an SLE Disease Activity Index (SLEDAI) score of at least 6 or at least one moderately to severely active manifestation scoring B or A on British Isles Lupus Assessment Group (BILAG) Index.
• May be taking up to 30 mg oral prednisone daily (or equivalent steroid) that has been stable for ≥ two weeks at the Baseline Visit.
• May be taking antimalarial treatment at any tolerated dose that has been stable for ≥ two months at the Baseline Visit.
• , May be taking one oral or injectable standard of care immunosuppressant defined as: Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent through Day 0: (i) Azathioprine ≤200 mg/day (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine) (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week
• \. Non steroidal anti-inflammatory drugs (NSAIDS), topical or ocular steroids, or topical or ocular calcineurin inhibitors are allowed with any dosing schedule (prn or fixed dosing).
• \. Female subjects must use 2 effective methods of avoiding pregnancy, only one of which is a barrier method, from the time they sign consent until 12 weeks after the last dose of study medication unless the subject is surgically sterile (e.g. bilateral oophorectomy or complete hysterectomy), has a sterile male partner, is at least 1 year postmenopausal, or practices sustained abstinence consistent with the subject's customary lifestyle. Postmenopausal is defined as at least 1 year since last menses and the subject has an elevated follicle-stimulating hormone (FSH) level greater than the threshold laboratory value of post-menopausal at screening. Effective methods of birth control include those listed in Appendix 12.8. Ineffective methods that should not be used are listed in Appendix 12.9
• \. All males (sterilized or non-sterilized) who are sexually active must use condom (with spermicide where commercially available for contraception) from Day 1 until at least 12 weeks after receipt of the final dose of IP. It is strongly recommended that the female partner of a male subject also use an effective method of contraception from Appendix 12,8 in the protocol (other than a barrier method) throughout this period. Male subjects must not donate sperm during the course of the study and for 12 weeks after the last dose of the investigational product.
• \. Females with an intact cervix must have documentation of a normal Pap smear with no documented malignancy or abnormalities (e.g., cervical intraepithelial neoplasia grade III, carcinoma in situ, or adenocarcinoma in situ within 2 years prior to randomization. Any abnormal Pap smear result documented within 2 years prior to randomization must be repeated to confirm patient eligibility.
• \. Meets all of the following tuberculosis criteria:
• No signs or symptoms of active tuberculosis prior to or during Screening.
• No medical history suggestive of active tuberculosis.
• No recent contact with a person with active tuberculosis OR if there has been such contact, referral to a physician specializing in tuberculosis to undergo additional evaluation prior to randomization (documented comprehensively in source), and, if warranted, receipt of appropriate treatment for latent tuberculosis at or before the first administration of investigational product.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to all staff at the Coordinating Clinic and/or at the study site)
• Have already received the 2020-2021 quadrivalent influenza vaccine.
• Receipt of any of the following:
• Any live or attenuated vaccine within 8 weeks prior to signing the ICF. Administration of killed vaccines is acceptable as long as not the influenza vaccine.
• Bacillus Calmette-Guerin (BCG) vaccine within 1 year of signing the ICF
• Blood transfusion or receipt of blood products within 4 weeks prior to signing the informed consent form (ICF)
• For patients with active or ongoing nephritis there must be two proteinuria data points available within the last two months to confirm a stable protein/creatine ratio as defined by no increase of \> 400 mg/gm between the first and second collection. There may be a delay of up to two weeks between screening and baseline for a repeat protein/creatinine ratio to be performed. The criteria will apply to the most recent two tests.
• In the opinion of the investigator, the patient has any active, unstable organ-threatening manifestations of SLE. At the investigator's discretion there may be a delay of up to two weeks between screening and baseline for appropriate diagnostic testing to confirm this criterion is not met.
• Lactating or pregnant females or females who intend to become pregnant or begin breastfeeding anytime from initiation of Screening until the end of the 12-week safety follow-up period following last dose of IP.
• Spontaneous or induced abortion, still or live birth, or pregnancy ≤4 weeks prior to signing the informed consent form (ICF).
• 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 ≥1 year prior to Week 0 (Day 1).
• Recent infection requiring hospitalization or use of intravenous anti-infectives within four weeks of signing the informed consent form or oral anti-infectives within two weeks of baseline or known history of splenectomy.
• Hepatitis B surface antigen (HBsAg), OR

Sponsors & Collaborators

• Oklahoma Medical Research Foundation: lead
• NYU Langone Health: collaborator
• Yale University: collaborator
• Piedmont Heart Institute, Inc., Atlanta, GA: collaborator
• Columbia University: collaborator

Study Sites (5)

Yale University Medical Center

New Haven, Connecticut, 06501, United States

NOT YET RECRUITING

Piedmont Hospital

Atlanta, Georgia, 30309, United States

NOT YET RECRUITING

New York University Medical Center

New York, New York, 10019, United States

NOT YET RECRUITING

Columbia Unversity Medical Center

New York, New York, 10032, United States

NOT YET RECRUITING

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Related Publications (3)

• Crowe SR, Merrill JT, Vista ES, Dedeke AB, Thompson DM, Stewart S, Guthridge JM, Niewold TB, Franek BS, Air GM, Thompson LF, James JA. Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features. Arthritis Rheum. 2011 Aug;63(8):2396-406. doi: 10.1002/art.30388.

  PMID: 21598235 BACKGROUND

• Battafarano DF, Battafarano NJ, Larsen L, Dyer PD, Older SA, Muehlbauer S, Hoyt A, Lima J, Goodman D, Lieberman M, Enzenauer RJ. Antigen-specific antibody responses in lupus patients following immunization. Arthritis Rheum. 1998 Oct;41(10):1828-34. doi: 10.1002/1529-0131(199810)41:103.0.CO;2-T.

  PMID: 9778224 BACKGROUND

• Abu-Shakra M, Press J, Buskila D, Sukenik S. Influenza vaccination of patients with systemic lupus erythematosus: safety and immunogenecity issues. Autoimmun Rev. 2007 Sep;6(8):543-6. doi: 10.1016/j.autrev.2006.12.004. Epub 2007 Jan 9.

  PMID: 17854746 BACKGROUND

Related Links

• this is the institutional website of the sponsor. Ongoing research projects and further references can be found on that site

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

anifrolumab; Standard of Care; Azathioprine; Methotrexate; Mycophenolic Acid; Adrenal Cortex Hormones; Antimalarials

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Joan T Merrill, M.D.

  Member

  STUDY DIRECTOR

• Cristina Arriens, M.D.

  Clinical Assistant Member

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joan T Merrill, M.D.

CONTACT

14058222336; joan-merrill@omrf.org

Cristina Arriens, M.D.

CONTACT

14052717805; cristina-arriens@omrf.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: There will be no masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Groups will include ten SLE patients who receive anifrolumab added to standard of care and ten patients who receive only standard of care

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: January 27, 2021
• Study Start: January 20, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: March 22, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: one year after completion of the study
• Access Criteria: Our registry requires registry board approval and internal review board approval. Investigators may apply with a description of the planned project

Locations

US (5)