Primary Sjögren's SyndromePhase 2CVAY736X2201NCT02149420

PD of VAY736 in Patients With Primary Sjögren's Syndrome

A Phase 2 study testing VAY736 in people with Primary Sjögren's Syndrome, run by Novartis Pharmaceuticals at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Primary Sjögren's Syndrome
What is being tested?: VAY736
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 27 participants
Where: 1 siteGermany
Study dates: 23 May 2014to 7 Feb 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

Germany1 site

Novartis Investigative Site
Berlin, 10117

Other trials in Germany

About this study

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

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

Read the 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.

Conditions: Primary Sjögren's Syndrome
Being tested: VAY736, Placebo
Keywords: primary Sjögren's syndrome, pharmacodynamics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VAY736Drug
PlaceboDrug

Study groups in NCT02149420
Study group	Role	What they receive
VAY736 3 mg/kg	Experimental	single dose iv of VAY736 at a dose of 3mg/kg Receives: Drug: VAY736
VAY736 10 mg/kg	Experimental	single dose iv of VAY736 at a dose of 10mg/kg Receives: Drug: VAY736
Placebo	Placebo comparator	single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, week 12
Overall Incidence of Adverse Events
Number of subjects with Adverse Events during the double blind treatment period.
Measured: Baseline to Week 24

Secondary outcomes (12)

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.
Measured: Baseline, week 12
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.
Measured: Baseline, week 12
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.
Measured: Baseline, week 12
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).
Measured: Baseline, week 12
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).
Measured: Baseline, week 12
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.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Cmax
The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Tmax
The time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
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.
Measured: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

23 May 20147 Feb 2018

First posted29 May 2014 (estimated)
Study start23 May 2014
Primary completion7 Feb 2018
Study completion7 Feb 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Primary Sjögren's SyndromeStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02149420
Sponsor's protocol ID: CVAY736X2201
Other IDs: 2013-000250-22
Acronym: CVAY736X2201
Status last verified: Sep 2021
First submitted: 9 Sep 2013
Last updated: 4 Oct 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02149420
Acronym / sponsor ID: CVAY736X2201 / CVAY736X2201
Conditions: Primary Sjögren's Syndrome
Keywords: primary Sjögren's syndrome, pharmacodynamics
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 23 May 2014 (actual)
Primary completion: 7 Feb 2018 (actual)
Study completion: 7 Feb 2018 (actual)
First posted: 29 May 2014 (estimated)
Results: Posted 12 Feb 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
VAY736 3 mg/kg	Experimental	Drug: VAY736single dose iv of VAY736 at a dose of 3mg/kg
VAY736 10 mg/kg	Experimental	Drug: VAY736single dose iv of VAY736 at a dose of 10mg/kg
Placebo	Placebo comparator	Drug: Placebosingle dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VAY736	Drug	VAY736 10 mg/kg, VAY736 3 mg/kg
Placebo	Drug	Placebo

Primary outcome

Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI)
Time frame: Baseline, week 12
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
Time frame: Baseline to Week 24
Number of subjects with Adverse Events during the double blind treatment period.

12 secondary outcomes

Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI)
Time frame: Baseline, week 12
Change in Short Form (36) Health Survey (SF-36)
Time frame: Baseline, week 12
Change in Multidimensional Fatigue Inventory (MFI)
Time frame: Baseline, week 12
Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)
Time frame: Baseline, week 12
Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS)
Time frame: Baseline, week 12
VAY736 Serum Concentration - AUCinf
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - AUClast
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - CL
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Cmax
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - T1/2
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Tmax
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Vz
Time frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.

Results and safety

Results posted to the registry on 12 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	9	9
VAY736 3 mg/kg	6	5
VAY736 10 mg/kg	12	10

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

Time frame: Baseline, week 12. Mean (Standard Deviation). Unit: units on a scale

Measure	Placebo n = 9	VAY736 3 mg/kg n = 6	VAY736 10 mg/kg n = 12	VAY736 Combined n = 18
Baseline	11.1 (4.08)	14.5 (9.44)	11.5 (4.38)	12.5 (6.38)
Week 12	10.2 (5.29)	10.7 (7.69)	10.0 (5.36)	10.2 (6.01)
Change from Baseline to Week 12	-0.9 (2.98)	-3.8 (8.66)	-1.5 (3.00)	-2.3 (5.40)

Placebo vs VAY736 Combined: Mean Difference (Final Values): -0.93 (95% CI -5.007 to 3.180), p = 0.678, repeated measures Bayesian analysis

Population analysed: PD analysis set

Primary outcome: Overall Incidence of Adverse Events

Time frame: Baseline to Week 24. Count of participants. Unit: Participants

Measure	Placebo n = 9	VAY736 3 mg/kg n = 6	VAY736 10 mg/kg n = 12	VAY736 Combined n = 18
Subjects with AEs	8	6	11	17
Subjects with AEs within 24hr of infusion	2	6	11	17
Subjects with AEs post 24hr of infusion	8	6	8	14
Subjects with Study drug-related AEs	5	6	11	17
Subjects with Infusion related AEs	1	6	9	15

Population analysed: Safety analysis set

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date subject has provided informed consent until end of study (Week 28 or when B cell recovery was demonstrated, up to 3 years).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	1 of 9 (11.1%)	9 of 9 (100%)	0 of 9
VAY736 3mg/kg	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6
VAY736 10mg/kg	0 of 12 (0%)	11 of 12 (91.7%)	0 of 12
Open Label VAY736 10mg/kg	1 of 5 (20%)	5 of 5 (100%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VAY736 in people with Primary Sjögren's Syndrome, run by Novartis Pharmaceuticals at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (time frame: Baseline, week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02149420.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2021.