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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT02495129

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Sjögren's Syndrome	Drug: VAY736 lower dose Drug: VAY736 higher dose	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Sep 1, 2017

Anticipated Study Completion Date :

Sep 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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)	Drug: VAY736 lower dose Patients will receive a total number of 3 monthly subcutaneous injections with the lower dose of VAY736
Experimental: VA736 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)	Drug: VAY736 higher dose Patients will receive a total number of 3 monthly subcutaneous injections with the higher dose of VAY736

Arm

Intervention/Treatment

Experimental: 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)

Drug: VAY736 lower dose

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

Experimental: VA736 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)

Drug: VAY736 higher dose

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

Outcome Measures

Primary Outcome Measures

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)
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

Secondary Outcome Measures

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 - Area under the curve (AUC)
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 size of spleen and cervical lyph nodes by PET/CT imaging and ultrasound-aided size measurements
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS [12 weeks]
Assess salivary glands size and echostructure by ultrasound
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS [12 weeks]
Assess salivary gland function (quantitative) by salivary flow (stimulated and unstimulated)
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
To asses the pharmacokinetiks of VAY736 in pSS patients [12 weeks]
Multiple s.c. dose VAY736 PK parameter - Cmax
To asses the pharmacokinetiks of VAY736 in pSS patients [12 weeks]
Multiple s.c. dose VAY736 PK parameter - tmax
To asses the pharmacokinetiks of VAY736 in pSS patients [12 weeks]
Multiple s.c. dose VAY736 PK parameter - half live (t1/2)

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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