Anifrolumab Treatment for 24 Weeks in Patients With Primary Sjögren's Syndrome

NCT ID: NCT05383677

Last Updated: 2022-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-01

Study Completion Date

2024-08-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Sjogren's Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Anifrolumab

20 patients will receive anifrolumab treatment

Group Type ACTIVE_COMPARATOR

Anifrolumab

Intervention Type DRUG

Anifrolumab 300 mg will be administered in intravenous infusions once per 4 weeks, for a total treatment period of 24 weeks.

Placebo

10 patients will receive placebo treatment

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered in intravenous infusions once per 4 weeks, for a total treatment period of 24 weeks.

Interventions

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Anifrolumab

Anifrolumab 300 mg will be administered in intravenous infusions once per 4 weeks, for a total treatment period of 24 weeks.

Intervention Type DRUG

Placebo

Placebo will be administered in intravenous infusions once per 4 weeks, for a total treatment period of 24 weeks.

Intervention Type DRUG

Other Intervention Names

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Saphnelo

Eligibility Criteria

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Inclusion Criteria

1. Written informed consent
2. Female or male aged ≥18 years
3. Disease duration (time since diagnosis) ≤10 years. In case of pediatric-onset pSS a disease duration of ≤15 years is allowed if there is residual gland function (UWS≥0.01 or SWS≥0.1 ml/min).
4. Fulfilment of 2016 ACR-EULAR classification criteria for pSS (which includes focus score ≥1 in salivary gland biopsy and/or anti-SSA/Ro positivity), based on previous diagnostic examinations
5. Presence of anti-SSA antibodies
6. ESSDAI≥5 and/or ESSPRI≥5. ESSDAI≥5 implicates a moderate to high systemic disease activity and ESSPRI≥5 implicates that the patient-reported symptom state is unacceptable. At least 50% of patients need to fulfil the ESSDAI≥5 criterion. Inclusion of patients with low ESSDAI (\<5) should be discontinued when 15 included patients (50%) have a low ESSDAI.
7. Willingness to undergo a repeated parotid gland biopsy at baseline and 24 weeks after start treatment. If a recent parotid gland biopsy (within ≤1 year before the baseline visit) is available, and enough material of this parotid gland biopsy is available, this biopsy can be used as baseline sample.
8. Use of reliable method of contraception for participants of reproductive potential.
9. Vaccinated against COVID-19 (at least two COVID-19 vaccinations) or previous confirmed COVID-19 infection (from which the patient is recovered) in combination with at least one COVID-19 vaccination or a previous confirmed COVID-19 infection (from which the patients has recovered) in combination with a positive anti-SARS-CoV-2 antibody test.

Exclusion Criteria

1. Presence of any other connective tissue disease
2. Positive pregnancy test (urinary HCG) at screening or breast-feeding
3. History of alcohol or drug abuse
4. 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.
5. 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.
6. History of chronic or recurrent serious infections. (e.g. chronic pyelonephritis, osteomyelitis or bronchiectasis).
7. Subjects with serious bacterial infections within the last 3 months, unless treated and resolved with antibiotics.
8. Opportunistic infection requiring hospitilization or IV antimicrobial treatment within 3 years of randomization
9. Any infection requiring hospitalization or treatment with IV anti-infective medications not completed at least 4 weeks prior to signing the ICF.
10. 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).
11. Any clinical cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection that has not completely resolved within 12 weeks prior to signing the ICF.
12. 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.
13. 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.
14. Subjects who are positive for hepatitis B surface antigen, which will be tested during screening.
15. 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.
16. Subjects who have received any live or attenuated vaccines within 8 weeks prior to signing the ICF.
17. Blood transfusion or receipt of blood products within 4 weeks prior to signing the ICF.
18. 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.
19. Preceding treatment with biological DMARDs, including abatacept, anti-TNF or other monoclonal antibodies within 6 months, and rituximab within 12 months from baseline
20. Use of high-dose prednisone, less than 2 weeks before inclusion. Stable low dose (≤10 mg) is allowed.
21. Use of hydroxychloroquine, methotrexate, cyclophosphamide, cyclosporine, azathioprine, MMF and leflunomide less than 3 months ago.
22. Use of pilocarpine less than 1 month ago.
23. Lab abnormalities:

* Serum creatinine \> 2.8 mg/dl (250 μmol/l)
* ASAT or ALAT outside 2.5 x upper normal range of the laboratory
* Hb \< 9 g/dl (5.6 mmol/l) for males and 8.5 g/dl (5.3 mmol/l) for females
* Neutrophil granulocytes less than 0.5 x 109/l
* Platelet count less than 50 x 109/l
24. Any other laboratory test results that, in the opinion of the investigator, might place a subject at unacceptable risk for participation in the study.
25. A known history of allergy or reaction to any component of the IP formulation or history of anaphylaxis to any human gamma globuline therapy.
26. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
27. Previous enrolment or randomisation in the present study
28. Participation in another clinical study with an investigational drug during the last 6 months, or local investigational product during the last month
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hendrika Bootsma

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

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University Medical Centre Groningen

Groningen, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Hendrika Bootsma

Role: CONTACT

Phone: +315036129456

Email: [email protected]

Facility Contacts

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Hendrika Bootsma

Role: primary

Other Identifiers

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2022-000609-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ESR-21-21284

Identifier Type: -

Identifier Source: org_study_id