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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VAY736 lower dose | Experimental | 12 evaluable patients will be enrolled and randomized (at a ratio of 1:1) to receive either a lower dose or a higher dose of the study drug (VAY736) |
|
| VA736 higher dose | Experimental | 12 evaluable patients will be enrolled and randomized (at a ratio of 1:1) to receive either a lower dose or a higher dose of the study drug (VAY736) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VAY736 lower dose | Drug | Patients will receive a total number of 3 monthly subcutaneous injections with the lower dose of VAY736 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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: PET/CT imaging of pSS major salivary gland 3, 6 and 9 days after i.v. injection with [Zr- 89]rituximab | Part 1: 4 weeks |
| 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: 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 2: 4 weeks |
| 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: 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 | Part 3: 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Safety of multiple s.c. dosing of VAY736 in pSS patients as measured by safety assessments | AEs, vital signs, ECGs, safety laboratory parameters (Hematology, Biochmistry, Urinalysis) | 12 weeks |
| To asses the pharmacokinetiks of VAY736 in pSS patients |
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Part 1 and 3:
Inclusion Criteria:
Exclusion Criteria:
Part 2
Inclusion criteria:
- healthy male and female people 18-75 years of age
Exclusion criteria:
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| ID | Term |
|---|---|
| D012859 | Sjogren's Syndrome |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C000656267 | ianalumab |
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| VAY736 higher dose | Drug | Patients will receive a total number of 3 monthly subcutaneous injections with the higher dose of VAY736 |
|
Multiple s.c. dose VAY736 PK parameter - Area under the curve (AUC)
| 12 weeks |
| To assess the pharmacokinetiks of VAY736 in pSS patients | Multiple s.c. dose VAY736 PK parameter - Trough concentrations after multiple dose | 12 weeks |
| Assess the pharmacodynamic effect of VAY736 on circulating CD19+ B-cells in pSS | Multiple s.c. dose VAY736 PD parameter - depletion of B cells | 12 weeks |
| Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS | Assess size of spleen and cervical lyph nodes by PET/CT imaging and ultrasound-aided size measurements | 12 weeks |
| Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS | Assess salivary glands size and echostructure by ultrasound | 12 weeks |
| Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS | Assess salivary gland function (quantitative) by salivary flow (stimulated and unstimulated) | 12 weeks |
| Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS | Assess lacrimal gland function by Schirmer's test | 12 weeks |
| To evaluate the effect of two different VAY736 dose levels (s.c. q4w) on pSS disease activity | Assess the change in the EULAR Sjögren'sSyndrome Disease Activity Index (ESSDAI). | 12 weeks |
| To evaluate the effect of on self-reported outcomes in pSS patients | Multidimensional Fatigue Inventory (MFI-20); the short form 36 health Survey (SF-36); EULAR Sjögren's Syndorm Patient Reported Intensity (ESSPRI) | 12 weeks |
| To evaluate the change in the physician global assessment of patients's overall disease activity | Physician's visual anaglog scale (VAS) | 12 weeks |
| To evaluate the change in the patients global assessment of their disease activity | Patient's visual analogue scale (VAS) | 12 weeks |
| To assess the immunogenicity of VAY736 | Anti-VAY736 antibodies | 12 weeks |
| To assess the immunogenicity of a micodose of rituximab | Anti-rituximab antibodies | 25 weeks |
| To asses the pharmacokinetiks of VAY736 in pSS patients | Multiple s.c. dose VAY736 PK parameter - Cmax | 12 weeks |
| To asses the pharmacokinetiks of VAY736 in pSS patients | Multiple s.c. dose VAY736 PK parameter - tmax | 12 weeks |
| To asses the pharmacokinetiks of VAY736 in pSS patients | Multiple s.c. dose VAY736 PK parameter - half live (t1/2) | 12 weeks |
| D012216 |
| Rheumatic Diseases |
| D014987 | Xerostomia |
| D012466 | Salivary Gland Diseases |
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D015352 | Dry Eye Syndromes |
| D007766 | Lacrimal Apparatus Diseases |
| D005128 | Eye Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |