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

Primary Sjögren's Syndrome Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02495129
• Other study ID #: CVAY736X2103
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: July 8, 2015
• Last updated: April 19, 2017
• Start date: December 2015
• Est. completion date: September 2017

Study information

• Verified date: February 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Primary Sjögren's Syndrome
• Sjogren's Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	To asses the pharmacokinetiks of VAY736 in pSS patients	Multiple s.c. dose VAY736 PK parameter - Area under the curve (AUC)	12 weeks
Secondary	To assess the pharmacokinetiks of VAY736 in pSS patients	Multiple s.c. dose VAY736 PK parameter - Trough concentrations after multiple dose	12 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	To evaluate the change in the physician global assessment of patients's overall disease activity	Physician's visual anaglog scale (VAS)	12 weeks
Secondary	To evaluate the change in the patients global assessment of their disease activity	Patient's visual analogue scale (VAS)	12 weeks
Secondary	To assess the immunogenicity of VAY736	Anti-VAY736 antibodies	12 weeks
Secondary	To assess the immunogenicity of a micodose of rituximab	Anti-rituximab antibodies	25 weeks
Secondary	To asses the pharmacokinetiks of VAY736 in pSS patients	Multiple s.c. dose VAY736 PK parameter - Cmax	12 weeks
Secondary	To asses the pharmacokinetiks of VAY736 in pSS patients	Multiple s.c. dose VAY736 PK parameter - tmax	12 weeks
Secondary	To asses the pharmacokinetiks of VAY736 in pSS patients	Multiple s.c. dose VAY736 PK parameter - half live (t1/2)	12 weeks