Primary Sjögren's Syndrome (pSS)
Conditions
Keywords
Primary Sjögren's Syndrome, Blinatumomab for Injection, Dry eye disease
Brief summary
The goal of this clinical trial is to learn if blinatumomab works to treat moderate-to-severe primary Sjögren's Syndrome. It will also learn about the safety of low-dose blinatumomab. The main questions it aims to answer are: Is low-dose blinatumomab more effective in patients with moderate-to-severe primary Sjögren's Syndrome who have an inadequate response or intolerance to conventional treatment? How does blinatumomab affect B cells, antibody levels, and the immune system in these participants? Researchers will compare background treatment plus low-dose Blinatumomab with background treatment only to see if low-dose Blinatumomab works to treat moderate-to-severe primary Sjögren's Syndrome. Participants will: Receive background treatment for 24 weeks, including hydroxychloroquine 400 mg each day, methylprednisolone 8 mg each day, and sodium hyaluronate eye drops 4 times each day. If assigned to the blinatumomab group, receive blinatumomab by continuous intravenous infusion for 5 days during week 1 and again for 5 days during week 3. The dose will be 9 micrograms per day. Attend regular follow-up visits for clinical assessments, laboratory tests, and monitoring of treatment effectiveness and safety.
Interventions
DRUGBlinatumomab
Participants will receive low-dose, short-course blinatumomab treatment. The dosing regimen is as follows: 1. First cycle: blinatumomab 9 μg/day by continuous intravenous infusion for 5 consecutive days, for a total dose of 45 μg. 2. Second cycle: the same dose and administration schedule will be repeated 1 week later.
All the participants will receive background treatment for 24 weeks. The background treatment includes: (1) hydroxychloroquine, 400 mg/day; (2) methylprednisolone, 8 mg/day; and (3) sodium hyaluronate eye drops, 4 times/day.
Sponsors
Beijing Tongren Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Participants who voluntarily agree to comply with the study protocol and provide written informed consent. 2. Male or female participants aged 18 to 70 years. 3. Diagnosis of primary Sjögren's syndrome according to the 2016 ACR/EULAR classification criteria. 4. Positive anti-SSA antibody at screening. 5. Moderate-to-severe active primary Sjögren's syndrome at screening, defined as an EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of ≥5. 6. Inadequate response or intolerance to conventional treatment, defined as having received at least one immunomodulatory therapy, including glucocorticoids, cyclophosphamide, antimalarial drugs, azathioprine, or biologic agents, for more than 6 months before screening, with unsatisfactory disease control based on ESSDAI or other clinical assessments, or recurrence of active disease after an initial treatment response. 7. Diagnosis of dry eye disease according to the 2024 Chinese Expert Consensus on the Clinical Diagnosis and Treatment of Dry Eye. 8. Moderate-to-severe dry eye disease at screening. 9. Laboratory values meeting all of the following requirements: * Absolute lymphocyte count ≥0.5 × 10⁹/L * Peripheral blood CD19+ B-cell count ≥25 cells/µL * Absolute neutrophil count ≥1.0 × 10⁹/L * Hemoglobin ≥8 g/dL * Platelet count ≥75 × 10⁹/L * Total bilirubin ≤1.5 × upper limit of normal (ULN), except for participants with confirmed Gilbert syndrome * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0 × ULN * Estimated glomerular filtration rate ≥30 mL/min/1.73 m², calculated using the CKD-EPI equation 10. Both eyes will undergo study-related examinations and treatment.
Exclusion criteria
1. Secondary Sjögren's syndrome. 2. Severe cardiovascular, hepatic, renal, respiratory, endocrine, or malignant disease, or uncontrolled acute or chronic infection. 3. Active and severe central nervous system manifestations related to Sjögren's syndrome. 4. History of stroke, epilepsy, dementia, Parkinson's disease, ataxia, cerebellar disease, psychosis, paresis, aphasia, or any other neurological condition that, in the investigator's judgment, may place the participant at excessive risk or interfere with study assessments. 5. Active ocular infection. 6. Other severe ocular diseases or ocular trauma diagnosed within 6 months before enrollment, including glaucoma, uveitis, retinal disease, chemical injury, or thermal burns. 7. Ocular surgery, including cataract surgery, within 6 months before enrollment. 8. Use of other eye drops that may affect the study outcomes. 9. Participation in another interventional clinical study. 10. Pregnancy or breastfeeding, or plans to become pregnant during the study period. 11. Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NEI corneal fluorescein staining score | Baseline and Week 24 | Corneal epithelial damage will be assessed using the National Eye Institute (NEI) corneal fluorescein staining scale. Each cornea is divided into five regions, and each region is scored from 0 to 3. The total score ranges from 0 to 15, with higher scores indicating more severe corneal epithelial damage. The outcome is calculated as the Week 24 total score minus the baseline score. A decrease of 3 points or more from baseline is defined as a response. |
| ESSDAI score | Baseline and Week 24 | Systemic disease activity will be assessed using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). The ESSDAI evaluates disease activity across 12 organ or system domains and has a total score ranging from 0 to 123, with higher scores indicating greater disease activity. The outcome is calculated as the Week 24 total score minus the baseline score. A decrease of 3 points or more from baseline is defined as a response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NEI score at follow-up visits | Baseline and Weeks 2, 4, 8, 12, 16, and 20 | Corneal epithelial damage will be assessed using the National Eye Institute corneal fluorescein staining scale. The total score ranges from 0 to 15, with higher scores indicating more severe corneal epithelial damage. Changes from baseline will be assessed at each prespecified follow-up visit. |
| OSDI score | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Dry eye symptoms and their effects on visual function and quality of life will be assessed using the 12-item Ocular Surface Disease Index (OSDI). The total score ranges from 0 to 100, with higher scores indicating more severe symptoms and greater impairment. Changes from baseline will be assessed at each follow-up visit. |
| FBUT | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Tear film stability will be assessed using fluorescein tear film break-up time (FBUT). FBUT is measured in seconds from eye opening until the first break in the fluorescein-stained tear film is observed. Measurements will be repeated for each eye and averaged according to the study protocol. Changes from baseline will be assessed at each follow-up visit. |
| Schirmer I test | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Tear secretion will be assessed using the Schirmer I test without topical anesthesia. A standard filter paper strip is placed in the lower conjunctival sac, and the length of wetting is measured in millimeters after 5 minutes. Changes from baseline will be assessed at each follow-up visit. |
| NIBUT | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Tear film stability will be assessed using non-invasive tear film break-up time (NIBUT) measured with an ocular surface analyzer. The instrument records the time from completion of a blink to the first detected tear film break. Measurements are generally repeated three times and averaged. Changes from baseline will be assessed at each follow-up visit. |
| Tear meniscus height | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Tear secretion and distribution will be assessed by measuring lower tear meniscus height using an ocular surface analyzer. The upper and lower boundaries of the lower tear meniscus beneath the central pupil are identified, and tear meniscus height is calculated in millimeters. Changes from baseline will be assessed at each follow-up visit. |
| Tear film lipid layer thickness | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Tear film lipid layer thickness will be measured using an ocular surface analyzer to assess meibomian gland-related tear film function. Lipid layer thickness is quantified using interference color units, with 1 interference color unit corresponding to approximately 1 nm. Changes from baseline will be assessed at each follow-up visit. |
| Incomplete blink rate | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Blinking behavior will be assessed using an ocular surface analyzer. The incomplete blink rate is calculated as the number of incomplete blinks divided by the total number of blinks during the observation period and expressed as a percentage. Changes from baseline will be assessed at each follow-up visit. |
| ESSDAI at follow-up visits | Baseline and Weeks 2, 4, 8, 12, 16, and 20 | Systemic disease activity will be assessed using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), which evaluates 12 organ or system domains. Higher scores indicate greater disease activity. Changes from baseline will be assessed at prespecified follow-up visits. |
| ESSPRI | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Patient-reported symptoms will be assessed using the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI). The ESSPRI evaluates dryness, fatigue, and pain on 0-to-10 numeric rating scales. The total score is the average of the three domain scores, with higher scores indicating more severe symptoms. Changes from baseline will be assessed at each follow-up visit. |
| MFI-20 | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Fatigue will be assessed using the 20-item Multidimensional Fatigue Inventory (MFI-20), which includes general fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. The total score ranges from 20 to 100, with higher scores indicating greater fatigue. Changes from baseline will be assessed at each follow-up visit. |
| Unstimulated salivary flow rate | Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24 | Salivary gland function will be assessed by measuring unstimulated whole salivary flow. Participants will collect saliva at rest for 15 minutes, and the salivary flow rate will be calculated in milliliters per minute. Changes from baseline will be assessed at each follow-up visit. |
| Autoantibody titers | Baseline and Weeks 4, 12, and 24 | Serum autoantibodies, including anti-SSA/Ro, anti-SSB/La, anti-dsDNA, anti-Sm, anti-RNP, antinuclear antibodies (ANA), and antineutrophil cytoplasmic antibodies (ANCA), will be measured. Changes in antibody titers from baseline will be assessed. The proportion of participants whose antibody status changes from positive to negative will also be evaluated. |
| Immunoglobulin levels | Baseline and Weeks 2, 4, 12, and 24 | Serum immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) concentrations will be measured to assess changes in humoral immune status. Changes from baseline will be evaluated, with particular attention to changes in IgG levels. |
| Peripheral blood lymphocyte subsets | Baseline and Weeks 2, 4, 12, and 24 | Peripheral blood lymphocyte subsets will be assessed by flow cytometry. Absolute counts of lymphocyte subsets and detailed B-cell subsets will be measured to evaluate the effects of treatment on B cells and T cells. |
| BCR/TCR repertoire | Baseline and Weeks 4, 12, and 24 | B-cell receptor (BCR) and T-cell receptor (TCR) repertoires will be assessed by high-throughput sequencing of lymphocytes isolated from peripheral blood. Changes in immune repertoire characteristics at follow-up visits will be compared with baseline as an exploratory assessment of treatment effects on adaptive immunity. |
| Adverse events | From baseline through Week 24 | Safety will be assessed by recording adverse events (AEs), serious adverse events (SAEs), adverse events leading to treatment discontinuation, clinically significant laboratory abnormalities, electrocardiogram abnormalities, and changes in vital signs. Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). |
Countries
China
Contacts
CONTACTBowen Wang, PhD
Outcome results
None listed