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About
The ANISE-II study is a randomized, double-blind, placebo-controlled phase IIa proof-of-concept trial. Thirty patients with primary Sjögren's syndrome (pSS) are randomized in a 2:1 ratio to either anifrolumab or placebo treatment for 24 weeks. Main inclusion criteria are fulfilment of the ACR/EULAR classification criteria for pSS, disease duration of ≤10 years, and an ESSDAI and/or ESSPRI of ≥5 (at least 50% of patients need to fulfil the ESSDAI ≥5 criterion). The primary outcome measure is Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS) response at week 24.
Full description
The aim is to evaluate safety and determine the effects of anifrolumab on essential clinical and biological parameters in patients with primary Sjögren's syndrome (pSS). Although the pathogenesis of pSS has not been fully elucidated, one of the key immune pathways involved is type-I IFN signalling. Since anifrolumab is a fully human, IgG1κ monoclonal antibody to type-I interferon receptor subunit 1, the hypothesis is that inhibition of type-I IFN signalling by anifrolumab may reduce glandular and systemic inflammation and attenuate disease activity in patients with pSS. The study population will consist of patients who fulfil 2016 ACR-EULAR criteria for pSS and have active disease, defined by a EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score ≥5 and/or an unacceptable patient symptom state (EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) score ≥5. The primary endpoint is the Composite of Relevant Endpoints for Sjögren's Syndrome (CRESS) at week 24.
Enrollment
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Inclusion criteria
Exclusion criteria
Presence of any other connective tissue disease
Positive pregnancy test (urinary HCG) at screening or breast-feeding
History of alcohol or drug abuse
History of malignancy or with a current suspicion for cancer, apart from local MALT lymphoma, squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥3 months prior to week 0 or cervical cancer in situ treated with apparent success with curative therapy ≥1 year prior to week 0.
Subjects with evidence (as assessed by the investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of HIV which will be tested during screening.
History of chronic or recurrent serious infections. (e.g. chronic pyelonephritis, osteomyelitis or bronchiectasis).
Subjects with serious bacterial infections within the last 3 months, unless treated and resolved with antibiotics.
Opportunistic infection requiring hospitilization or IV antimicrobial treatment within 3 years of randomization
Any infection requiring hospitalization or treatment with IV anti-infective medications not completed at least 4 weeks prior to signing the ICF.
Subjects with herpes zoster that resolved less than 12 weeks before potential enrollment or any severe case of herpes zoster in a subjects history, including, but not limited to, non-cutaneous herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes involving the retina (ever).
Any clinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection that has not completely resolved within 12 weeks prior to signing the ICF.
Any history of severe COVID-19 infection (e.g. requiring hospitalization, ICU care or assisted ventilation) or any prior COVID-19 infection with unresolved sequelae. Any acute COVID-19 infection (lab confirmed or suspected based on clinical symptoms) within the last 3 months prior to screening.
Subjects at risk for TB. Specifically excluded from this study will be subjects with a history of active TB; current clinical, radiographic, or laboratory evidence of active TB, which will be tested during screening; history of latent TB, with the exception of latent TB with documented completion of appropriate treatment.
Subjects who are positive for hepatitis B surface antigen, which will be tested during screening.
Subjects who are positive for hepatitis C antibody if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay, which will be tested during screening.
Subjects who have received any live or attenuated vaccines within 8 weeks prior to signing the ICF.
Blood transfusion or receipt of blood products within 4 weeks prior to signing the ICF.
Underlying cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal, hematological or neurological conditions, chronic or latent infectious diseases or immune deficiency which places the patient at an unacceptable risk for participation in the study.
Preceding treatment with biological DMARDs, including abatacept, anti-TNF or other monoclonal antibodies within 6 months, and rituximab within 12 months from baseline
Use of high-dose prednisone, less than 2 weeks before inclusion. Stable low dose (≤10 mg) is allowed.
Use of hydroxychloroquine, methotrexate, cyclophosphamide, cyclosporine, azathioprine, MMF and leflunomide less than 3 months ago.
Use of pilocarpine less than 1 month ago.
Lab abnormalities:
Any other laboratory test results that, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
A known history of allergy or reaction to any component of the IP formulation or history of anaphylaxis to any human gamma globuline therapy.
Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
Previous enrolment or randomisation in the present study
Participation in another clinical study with an investigational drug during the last 6 months, or local investigational product during the last month
Primary purpose
Allocation
Interventional model
Masking
30 participants in 2 patient groups, including a placebo group
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Central trial contact
Hendrika Bootsma
Data sourced from clinicaltrials.gov
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