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PD of VAY736 in Patients With Primary Sjögren's Syndrome (CVAY736X2201)

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ClinicalTrials.gov Identifier: NCT02149420
Recruitment Status : Completed
First Posted : May 29, 2014
Results First Posted : February 12, 2019
Last Update Posted : October 4, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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

Condition or disease Intervention/treatment Phase
Primary Sjögren's Syndrome Drug: VAY736 Drug: Placebo Phase 2

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
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes 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).
Primary Purpose: Treatment
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
Actual Study Start Date : May 23, 2014
Actual Primary Completion Date : February 7, 2018
Actual Study Completion Date : February 7, 2018

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: VAY736 3 mg/kg
single dose iv of VAY736 at a dose of 3mg/kg
 Drug: VAY736
Experimental: VAY736 10 mg/kg
single dose iv of VAY736 at a dose of 10mg/kg
 Drug: VAY736
Placebo Comparator: Placebo
single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg.
 Drug: Placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. Overall Incidence of Adverse Events [ Time Frame: Baseline to Week 24 ]
    Number of subjects with Adverse Events during the double blind treatment period.


Secondary Outcome Measures :
  1. Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI) [ Time Frame: Baseline, week 12 ]
    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.

  2. Change in Short Form (36) Health Survey (SF-36) [ Time Frame: Baseline, week 12 ]
    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.

  3. Change in Multidimensional Fatigue Inventory (MFI) [ Time Frame: Baseline, week 12 ]
    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.

  4. Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS) [ Time Frame: Baseline, week 12 ]
    The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

  5. Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS) [ Time Frame: Baseline, week 12 ]
    The visual analogue scale used is a 100 mm VAS ranging from "no disease" (0 mm) to "maximal disease activity" (100 mm).

  6. VAY736 Serum Concentration - AUCinf [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    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.

  7. VAY736 Serum Concentration - AUClast [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    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.

  8. VAY736 Serum Concentration - CL [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    The systemic (or total body) clearance from serum following intravenous administration [volume / time]. The concentration of VAY736 was measured in the serum.

  9. VAY736 Serum Concentration - Cmax [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum.

  10. VAY736 Serum Concentration - T1/2 [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    Apparent terminal half-life, determined as the ln2/lambda_z or 0.693/lambda_z. The concentration of VAY736 was measured in the serum.

  11. VAY736 Serum Concentration - Tmax [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    The time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum.

  12. VAY736 Serum Concentration - Vz [ Time Frame: 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. ]
    The volume of distribution during the terminal elimination phase following intravenous administration [volume]. The concentration of VAY736 was measured in the serum.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02149420


Locations
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Germany
Novartis Investigative Site
Berlin, Germany, 10117
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] October 31, 2016
Statistical Analysis Plan  [PDF] January 11, 2017

More Information
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Additional Information:

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02149420    
Other Study ID Numbers: CVAY736X2201
2013-000250-22 ( EudraCT Number )
First Posted: May 29, 2014    Key Record Dates
Results First Posted: February 12, 2019
Last Update Posted: October 4, 2021
Last Verified: September 2021
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
primary Sjögren's syndrome, pharmacodynamics
Additional relevant MeSH terms:
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Sjogren's Syndrome
Syndrome
Disease
Pathologic Processes
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Xerostomia
 Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases
Dry Eye Syndromes
Lacrimal Apparatus Diseases
Eye Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases