PD of VAY736 in Patients With Primary Sjögren's Syndrome - Clinical Trial for Primary Sjögren's Syndrome | NCT02149420

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

VAY736

Placebo

About this trial

This is an interventional treatment trial for Primary Sjögren's Syndrome focused on measuring primary Sjögren's syndrome, pharmacodynamics

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA:

Fulfilled revised European US consensus criteria for pSS
ESSDAI value ≥ 6
Elevated serum titers at screening of ANA (≥ 1:160)
Seropositive at screening for anti-SSA and/or anti-SSB antibodies
Stimulated whole salivary flow rate at screening of > 0 mL/min

EXCLUSION CRITERIA:

- Prior or previous use of (specific dosages and intervals prior to study start may apply): B-cell depleting therapy (e.g., rituximab), Prednisone, anti-BAFF mAb, CTLA4-Fc Ig (abatacept), anti-TNF-α mAb, cyclophosphamide, azathioprine and medications known to cause dry mouth.

Hydroxychloroquine or methotrexate in a consistent dose for ≥ 3 months prior to randomization is allowed

Active or recent history of clinically significant infection
Vaccination within 2 month prior to study
History of primary or secondary immunodeficiency

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

VAY736 3 mg/kg

VAY736 10 mg/kg

Placebo

Arm Description

single dose iv of VAY736 at a dose of 3mg/kg

single dose iv of VAY736 at a dose of 10mg/kg

single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg.

Outcomes

Primary Outcome Measures

Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)

The effect of VAY736 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients.

Overall Incidence of Adverse Events

Number of subjects with Adverse Events during the double blind treatment period.

Secondary Outcome Measures

Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms. During the study all individual scores were reported as 1 to 10 instead. A linear transformation was reported to map the scores to the range of 0-10.

Change in Short Form (36) Health Survey (SF-36)

The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.

Change in Multidimensional Fatigue Inventory (MFI)

The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a posible range from 4-20. A reduction from baseline in MFI indicates improvement.

Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)

The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)

The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

VAY736 Serum Concentration - AUCinf

The area under the serum concentration-time curve from time zero to infinity [mass × time / volume]. The concentration of VAY736 was measured in the serum.

VAY736 Serum Concentration - AUClast

The area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration [mass × time / volume]. The concentration of VAY736 was measured in the serum.

VAY736 Serum Concentration - CL

The systemic (or total body) clearance from serum following intravenous administration [volume / time]. The concentration of VAY736 was measured in the serum.

VAY736 Serum Concentration - Cmax

The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.

VAY736 Serum Concentration - T1/2

Apparent terminal half-life, determined as the ln2/lambda_z or 0.693/lambda_z. The concentration of VAY736 was measured in the serum.

VAY736 Serum Concentration - Tmax

The time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.

VAY736 Serum Concentration - Vz

The volume of distribution during the terminal elimination phase following intravenous administration [volume]. The concentration of VAY736 was measured in the serum.

Full Information

NCT ID

NCT02149420

First Posted

September 9, 2013

Last Updated

September 30, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02149420

Brief Title

PD of VAY736 in Patients With Primary Sjögren's Syndrome

Acronym

CVAY736X2201

Official Title

A Single Dose, Double-blind, Placebo-controlled, Parallel Study to Assess the Pharmacodynamics, Pharmacokinetics and Safety and Tolerability of VAY736 in Patients With Primary Sjögren's Syndrome

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

May 23, 2014 (Actual)

Primary Completion Date

February 7, 2018 (Actual)

Study Completion Date

February 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

This study was designed to evaluate the safety, tolerability, pharmacokinetics and therapeutic efficacy of a single intravenous infusion of VAY7346 monoclonal antibody in pSS patients

Detailed Description

Patients were enrolled in 2 sequential cohorts: Cohort 1: 6 patients received 3 mg/kg or Placebo (2:1 ratio) Cohort 2: 21 patients received 10 mg/kg, 3 mg/kg or Placebo (6:1:3 ratio) At week 24 the blind was broken to assess continuation in the trial: If a patient received VAY736 and their B cell recovery was demonstrated at Week 24, then patients completed the trial. If a patient received VAY736 and their B cell recovery was NOT demonstrated at Week 24, then patients were followed up until B cell recovery was demonstrated If a patient received placebo, they were offered the option of receiving open-label VAY736 (10 mg/kg) in a separate treatment arm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Sjögren's Syndrome

Keywords

primary Sjögren's syndrome, pharmacodynamics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Treatment was unblinded at an individual patient level at Week 24 to determine their progress in the study (follow-up, open-label VAY736 or End of Study Visit).

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

VAY736 3 mg/kg

Arm Type

Experimental

Arm Description

single dose iv of VAY736 at a dose of 3mg/kg

Arm Title

VAY736 10 mg/kg

Arm Type

Experimental

Arm Description

single dose iv of VAY736 at a dose of 10mg/kg

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg.

Intervention Type

Drug

Intervention Name(s)

VAY736

Intervention Type

Drug

Intervention Name(s)

Placebo

Primary Outcome Measure Information:

Title

Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)

Description

The effect of VAY736 on clinical disease activity was measured by the change in ESSDAI (EULAR Sjögren's syndrome disease activity index) between baseline and week 12. The instrument contains 12 organ-specific domains contributing to disease activity. For each domain, features of disease activity are scored in 3 or 4 levels according to their severity. These scores are then summed across the 12 domains in a weighted manner to provide the total score (range 0-123). A reduction from baseline indicates improvement in patients.

Time Frame

Baseline, week 12

Title

Overall Incidence of Adverse Events

Description

Number of subjects with Adverse Events during the double blind treatment period.

Time Frame

Baseline to Week 24

Secondary Outcome Measure Information:

Title

Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)

Description

The ESSPRI is a patient self-reported outcome measure to assess dryness, limb pain, fatigue and mental fatigue, where each of the domains normally reported as 0 (not at all) to 10 (extremely severe). The final ESSPRI score is the average of three: dryness, pain and fatigue. A reduction from baseline indicates the improvement of symptoms. During the study all individual scores were reported as 1 to 10 instead. A linear transformation was reported to map the scores to the range of 0-10.

Time Frame

Baseline, week 12

Title

Change in Short Form (36) Health Survey (SF-36)

Description

The SF-36 is a 36-item, patient self-reported outcome measure (questionnaires) of patient health. The outcome of the questionnaires in eight scales results in two summary scores, physical component and mental component, both ranging from 0 - 100. An increase from baseline in either component summary score indicates reduced disease burden.

Time Frame

Baseline, week 12

Title

Change in Multidimensional Fatigue Inventory (MFI)

Description

The MFI is a patient self-reported outcome measure (questionnaires) to assess fatigue covering the following dimensions: General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity. Each dimension has a posible range from 4-20. A reduction from baseline in MFI indicates improvement.

Time Frame

Baseline, week 12

Title

Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)

Description

The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

Time Frame

Baseline, week 12

Title

Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)

Description

The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

Time Frame

Baseline, week 12

Title

VAY736 Serum Concentration - AUCinf

Description

The area under the serum concentration-time curve from time zero to infinity [mass × time / volume]. The concentration of VAY736 was measured in the serum.

Time Frame