Study of Pharmacodynamic Effects of VAY736 in Patients With Primary Sjögren's Syndrome
- Conditions
- Primary Sjögren's Syndrome
- Interventions
- Drug: VAY736 lower doseDrug: VAY736 higher dose
- Registration Number
- NCT02495129
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 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.
- 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
Exclusion criteria:
- Use of other investigational drugs at the time of enrollment
- Exposure to a sizeable degree of radiation (≥ 5 mSv) in an investigational research study in the past year prior to this study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VAY736 lower dose VAY736 lower dose 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 VAY736 higher dose 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)
- Primary Outcome Measures
Name Time Method 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
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)
- Secondary Outcome Measures
Name Time Method 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 - half live (t1/2)
To assess the pharmacokinetiks of VAY736 in pSS patients 12 weeks Multiple s.c. dose VAY736 PK parameter - Trough concentrations after multiple dose
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
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS 12 weeks Assess lacrimal gland function by Schirmer's test
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)
To evaluate the change in the physician global assessment of patients's overall disease activity 12 weeks Physician's visual anaglog scale (VAS)
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