Clinical trial NCT02495129: Study of Pharmacodynamic Effects of VAY736 in Patients With Primary Sjögren's Syndrome
Official title: A Three-part, Partially Open Label and Double-blind, Randomized Study to Assess the Pharmacodynamic Effects, Safety, Tolerability and Preliminary Efficacy of VAY736 in Patients With Primary Sjögren's Syndrome Using [Zr-89]-Rituximab PET/CT
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Primary Sjögren's Syndrome
Keywords: Primary Sjögren's syndrome
Sicca syndrome
Salivary glands
Positron Emission Tomography
B cell depletion
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-07-13
Enrollment: 0
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

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

Primary outcomes:
measure: Part 1: To determine the feasibility of measuring major salivary gland infiltrating B cells in pSS patients using [Zr- 89]rituximab PET/CT imaging
timeFrame: Part 1: 4 weeks
measure: 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
timeFrame: Part 2: 4 weeks
measure: 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
timeFrame: Part 3: 12 weeks
Secondary outcomes:
measure: Safety of multiple s.c. dosing of VAY736 in pSS patients as measured by safety assessments
timeFrame: 12 weeks
measure: To asses the pharmacokinetiks of VAY736 in pSS patients
timeFrame: 12 weeks
measure: To assess the pharmacokinetiks of VAY736 in pSS patients
timeFrame: 12 weeks
measure: Assess the pharmacodynamic effect of VAY736 on circulating CD19+ B-cells in pSS
timeFrame: 12 weeks
measure: Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
timeFrame: 12 weeks
measure: Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
timeFrame: 12 weeks
measure: Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
timeFrame: 12 weeks
measure: Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
timeFrame: 12 weeks
measure: To evaluate the effect of two different VAY736 dose levels (s.c. q4w) on pSS disease activity
timeFrame: 12 weeks
measure: To evaluate the effect of on self-reported outcomes in pSS patients
timeFrame: 12 weeks
measure: To evaluate the change in the physician global assessment of patients's overall disease activity
timeFrame: 12 weeks
measure: To evaluate the change in the patients global assessment of their disease activity
timeFrame: 12 weeks
measure: To assess the immunogenicity of VAY736
timeFrame: 12 weeks
measure: To assess the immunogenicity of a micodose of rituximab
timeFrame: 25 weeks
measure: To asses the pharmacokinetiks of VAY736 in pSS patients
timeFrame: 12 weeks
measure: To asses the pharmacokinetiks of VAY736 in pSS patients
timeFrame: 12 weeks
measure: To asses the pharmacokinetiks of VAY736 in pSS patients
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
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