Primary Sjögren's Syndrome
Conditions
Keywords
Primary Sjögren's syndrome, Sicca syndrome, Salivary glands, Positron Emission Tomography, B cell depletion
Brief summary
This study consists of three consecutive parts. Part 1 in primary Sjögren's syndrome (pSS) patients (n=2-6) and Part 2 in healthy voluteers (n=3) are feasibility studies to assess if the selected \[Zr-89\]-rituximab PET/CT method is a valid method to assess B cells in salivary glands of pSS patients. In Part 1 and Part 2 no IMP will be applied to the subjects. In Part 3, pSS patients (n=12) will receive the IMP, VAY736. Posted information will be focused on Part 3. The overarching purpose of this study is to test a new drug (VAY736) for the treatment of pSS. In pSS, the salivary glands (the glands that produce saliva) and other organs are affected by inflammation. A certain type of white blood cells called B cells prominently infiltrate the salivary glands in pSS, whereas they are not present in healthy salivary glands. Scientific evidence suggests that B cells may be involved in the disease process in pSS and that eliminating B cells may benefit patients with pSS. This study will test a new imaging method and a new treatment for pSS. Both the imaging method and the treatment are specific for B cells.
Interventions
DRUGVAY736 lower dose
Patients will receive a total number of 3 monthly subcutaneous injections with the lower dose of VAY736
DRUGVAY736 higher dose
Patients will receive a total number of 3 monthly subcutaneous injections with the higher dose of VAY736
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
Part 1 and 3: Inclusion Criteria: * Fullfilled consensus criteria for primary Sjögren's syndrome * Patients must have elevated serum levels for some Sögren Syndorme specific parameters such as antinuclear antibodies (ANA), rheumatoid factor (RF) etc.
Exclusion criteria
* Patients that are suffering from Secondary Sjögren's syndrome. * Patients previously treated with monoclonal antibody treatments such as rituximab, infliximab, adalimumab, etc. Part 2 Inclusion criteria: \- healthy male and female people 18-75 years of age
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: To determine the feasibility of measuring major salivary gland infiltrating B cells in pSS patients using [Zr- 89]rituximab PET/CT imaging | Part 1: 4 weeks | Part 1: PET/CT imaging of pSS major salivary gland 3, 6 and 9 days after i.v. injection with \[Zr- 89\]rituximab |
| Part 2: To define the normal range of PET/CT imaging values for major salivary gland tissue, cervical lymph nodes and spleen in healthy volunteers with [Zr-89]-rituximab | Part 2: 4 weeks | Part 2: PET/CT imaging of healthy volunteers' major salivary gland, cervical lymph nodes and spleen on optimal time point after i.v. injection with \[Zr-89\]-rituximab (e.g. 3 days after injection) |
| Part 3: To compare the effect of two different VAY736 s.c. dose regimes on salivary gland-infiltrating B cells in pSS patients, using [Zr-89]-rituximab PET/CT imaging | Part 3: 12 weeks | Part 3: PET/CT imaging of pSS tissues on optimal time point after i.v. injection with \[Zr-89\]-rituximab, at baseline and 12 weeks after the start of VAY736 treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the pharmacokinetiks of VAY736 in pSS patients | 12 weeks | Multiple s.c. dose VAY736 PK parameter - Trough concentrations after multiple dose |
| Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS | 12 weeks | Assess size of spleen and cervical lyph nodes by PET/CT imaging and ultrasound-aided size measurements |
| To evaluate the effect of two different VAY736 dose levels (s.c. q4w) on pSS disease activity | 12 weeks | Assess the change in the EULAR Sjögren'sSyndrome Disease Activity Index (ESSDAI). |
| To evaluate the effect of on self-reported outcomes in pSS patients | 12 weeks | Multidimensional Fatigue Inventory (MFI-20); the short form 36 health Survey (SF-36); EULAR Sjögren's Syndorm Patient Reported Intensity (ESSPRI) |
| Assess the pharmacodynamic effect of VAY736 on circulating CD19+ B-cells in pSS | 12 weeks | Multiple s.c. dose VAY736 PD parameter - depletion of B cells |
| To evaluate the change in the patients global assessment of their disease activity | 12 weeks | Patient's visual analogue scale (VAS) |
| To assess the immunogenicity of VAY736 | 12 weeks | Anti-VAY736 antibodies |
| To assess the immunogenicity of a micodose of rituximab | 25 weeks | Anti-rituximab antibodies |
| To evaluate the change in the physician global assessment of patients's overall disease activity | 12 weeks | Physician's visual anaglog scale (VAS) |
| Safety of multiple s.c. dosing of VAY736 in pSS patients as measured by safety assessments | 12 weeks | AEs, vital signs, ECGs, safety laboratory parameters (Hematology, Biochmistry, Urinalysis) |
| To asses the pharmacokinetiks of VAY736 in pSS patients | 12 weeks | Multiple s.c. dose VAY736 PK parameter - Area under the curve (AUC) |
Outcome results
None listed