Primary Sjögren's syndrome. Patients will be included if the fulfil the 2016 ACR/EULAR classification criteria for pSS and if they have active disease according to an ESSDAI score of 5 or more and/or an ESSPRI score of 5 or more.
Conditions
Interventions
Trade Name: Saphnelo
Product Name: Anifrolumab
Pharmaceutical Form: Infusion
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use
Sponsors
University Medical Centre Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Written informed consent. - Female or male aged >= 18 years. - Disease duration =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 (= 40 kg. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: - Presence of any other connective tissue disease. - Positive pregnancy test at screening or breastfeeding. - 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 years 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. - 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 this 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To explore the clinical efficacy of anifrolumab in patients with primary Sjögren’s syndrome ;Secondary Objective: To determine the safety of anifrolumab and effects of anifrolumab on clinical, functional, subjective, laboratory and histopathological parameters in patients with primary Sjögren's syndrome;Primary end point(s): Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) response at week 24. The CRESS is a recently developed composite endpoint which consists of five clinically relevant items for pSS: a systemic disease activity, patient-reported symptoms, tear gland, salivary gland and serology item. A CRESS responder is someone who reached response on at least three out of five items. CRESS response at week 24 was selected as primary outcome measure since the CRESS is a comprehensive and clinically relevant composite endpoint which encompasses all of the major disease features of pSS. In our development and validation study, CRESS was able to lower placebo response in several randomised controlled trials (RCTs), compared to the ESSDAI score alone. Furthermore, the CRESS was able to demonstrate beneficial treatment effects of abatacept and rituximab in RCTs which did not meet their primary endpoint.;Timepoint(s) of evaluation of this end point: The primary endpoint will be evaluated at week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Safety (adverse events and tolerability) of anifrolumab by monitoring SAE and AE, treatment discontinuation related to SAE and AE, and lab abnormalities at weeks 0, 4, 8, 12, 16, 20 and 24 - Total CRESS response at week 12 - Individual CRESS items (continuous): ClinESSDAI (weeks 0, 8, 12, 20, 24), ESSPRI (weeks 0, 8, 12, 20, 24), Schirmer’s test (weeks 0, 12, 24), OSS (weeks 0, 12, 24), UWS (weeks 0, 12, 24), SGUS (Hocevar score) (weeks 0, 12, 24), RF and total IgG concentration in blood (weeks 0, 8, 12, 20, 24). - ESSDAI (continuous) (weeks 0, 4, 8, 12, 20, 24) - The (Clin)ESSDAI minimal clinically important improvement (MCII, defined as decrease of =3 points) and low disease activity (LDA, defined as score <5) (weeks 8, 12, 20, 24) - Physician GDA (weeks 0, 8, 12, 20, 24) - NRS score oral, ocular, and vaginal dryness and mental fatigue (weeks 0, 8, 12, 20, 24) - Patient GDA (weeks 0, 8, 12, 20, 24) - SF-36 health survey (weeks 0, 12, 24) - EQ-5D measure of health-related quality of life (weeks 0, 8, 12, 20, 24) - MFI scale (weeks 0, 12, 24) - FSFI in females (weeks 0, 12, 24) - SWS (weeks 0, 12, 24) - Parotid gland histology at baseline vs. week 24: focus score and area fraction of CD45+ infiltrate - Serum levels of anti-SSA/-SSB, complement (C3/C4), lymphocyte count, and presence of cryoglobulinemia (weeks 0, 8, 12, 20, 24) ;Timepoint(s) of evaluation of this end point: Assessments will be conducted at week 0, 4, 8, 12, 16, 20 and 24. Some of the outcome measures will be evaluated at all time points, and some of the outcome measures only at the most important timepoints (week 12 and 24). | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
University Medical Centre Groningen
Outcome results
None listed