Study of Pharmacodynamic Effects of VAY736 in Patients With Primary Sjögren's Syndrome

NCT02495129 | Withdrawn Phase 1

• 1 other identifier: CVAY736X2103
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Primary Sjögren's Syndrome

Keywords

Primary Sjögren's syndrome; Sicca syndrome; Salivary glands; Positron Emission Tomography; B cell depletion

Outcome Measures

Primary Outcomes (3)

• 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

Secondary Outcomes (17)

• Safety of multiple s.c. dosing of VAY736 in pSS patients as measured by safety assessments

  12 weeks

• To asses the pharmacokinetiks of VAY736 in pSS patients

  12 weeks

• To assess the pharmacokinetiks of VAY736 in pSS patients

  12 weeks

• Assess the pharmacodynamic effect of VAY736 on circulating CD19+ B-cells in pSS

  12 weeks

• Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS

  12 weeks

Study Arms (2)

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)

Drug: VAY736 lower dose

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)

Drug: VAY736 higher dose

Interventions

VAY736 lower dose DRUG

Patients will receive a total number of 3 monthly subcutaneous injections with the lower dose of VAY736

VAY736 lower dose

VAY736 higher dose DRUG

Patients will receive a total number of 3 monthly subcutaneous injections with the higher dose of VAY736

VA736 higher dose

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients that are suffering from Secondary Sjögren's syndrome.
• Patients previously treated with monoclonal antibody treatments such as rituximab, infliximab, adalimumab, etc.
• Part 2
• \- healthy male and female people 18-75 years of age
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Sjogren's Syndrome

Interventions

ianalumab

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 13, 2015
• Study Start: December 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: April 20, 2017

Record last verified: 2016-02