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

April 19, 2017 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: To determine the feasibility of measuring major salivary gland infiltrating B cells in pSS patients using [Zr- 89]rituximab PET/CT imaging
Time Frame: 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 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
Time Frame: 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 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
Time Frame: 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 3: 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety of multiple s.c. dosing of VAY736 in pSS patients as measured by safety assessments
Time Frame: 12 weeks
AEs, vital signs, ECGs, safety laboratory parameters (Hematology, Biochmistry, Urinalysis)
12 weeks
To asses the pharmacokinetiks of VAY736 in pSS patients
Time Frame: 12 weeks
Multiple s.c. dose VAY736 PK parameter - Area under the curve (AUC)
12 weeks
To assess the pharmacokinetiks of VAY736 in pSS patients
Time Frame: 12 weeks
Multiple s.c. dose VAY736 PK parameter - Trough concentrations after multiple dose
12 weeks
Assess the pharmacodynamic effect of VAY736 on circulating CD19+ B-cells in pSS
Time Frame: 12 weeks
Multiple s.c. dose VAY736 PD parameter - depletion of B cells
12 weeks
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
Time Frame: 12 weeks
Assess size of spleen and cervical lyph nodes by PET/CT imaging and ultrasound-aided size measurements
12 weeks
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
Time Frame: 12 weeks
Assess salivary glands size and echostructure by ultrasound
12 weeks
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
Time Frame: 12 weeks
Assess salivary gland function (quantitative) by salivary flow (stimulated and unstimulated)
12 weeks
Asses effect of two different VAY736 dose levels on target tissue structure and function in pSS
Time Frame: 12 weeks
Assess lacrimal gland function by Schirmer's test
12 weeks
To evaluate the effect of two different VAY736 dose levels (s.c. q4w) on pSS disease activity
Time Frame: 12 weeks
Assess the change in the EULAR Sjögren'sSyndrome Disease Activity Index (ESSDAI).
12 weeks
To evaluate the effect of on self-reported outcomes in pSS patients
Time Frame: 12 weeks
Multidimensional Fatigue Inventory (MFI-20); the short form 36 health Survey (SF-36); EULAR Sjögren's Syndorm Patient Reported Intensity (ESSPRI)
12 weeks
To evaluate the change in the physician global assessment of patients's overall disease activity
Time Frame: 12 weeks
Physician's visual anaglog scale (VAS)
12 weeks
To evaluate the change in the patients global assessment of their disease activity
Time Frame: 12 weeks
Patient's visual analogue scale (VAS)
12 weeks
To assess the immunogenicity of VAY736
Time Frame: 12 weeks
Anti-VAY736 antibodies
12 weeks
To assess the immunogenicity of a micodose of rituximab
Time Frame: 25 weeks
Anti-rituximab antibodies
25 weeks
To asses the pharmacokinetiks of VAY736 in pSS patients
Time Frame: 12 weeks
Multiple s.c. dose VAY736 PK parameter - Cmax
12 weeks
To asses the pharmacokinetiks of VAY736 in pSS patients
Time Frame: 12 weeks
Multiple s.c. dose VAY736 PK parameter - tmax
12 weeks
To asses the pharmacokinetiks of VAY736 in pSS patients
Time Frame: 12 weeks
Multiple s.c. dose VAY736 PK parameter - half live (t1/2)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2017

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 8, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 10, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 13, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CVAY736X2103

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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