PD of VAY736 in Patients With Primary Sjögren's Syndrome

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

Sponsoren

Hauptsponsor: Novartis Pharmaceuticals

Quelle Novartis
Kurze Zusammenfassung

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

detaillierte Beschreibung

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.

Gesamtstatus Completed
Anfangsdatum May 23, 2014
Fertigstellungstermin February 7, 2018
Primäres Abschlussdatum February 7, 2018
Phase Phase 2
Studientyp Interventional
Primärer Ausgang
Messen Zeitfenster
Change in EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Baseline, week 12
Overall Incidence of Adverse Events Baseline to Week 24
Sekundäres Ergebnis
Messen Zeitfenster
Change in EULAR Sjögren's Syndrome Patient Response Index (ESSPRI) Baseline, week 12
Change in Short Form (36) Health Survey (SF-36) Baseline, week 12
Change in Multidimensional Fatigue Inventory (MFI) Baseline, week 12
Change in the Physician's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS) Baseline, week 12
Change in the Patient's Global Assessment of Overall Disease Activity by Means of Visual Analog Scale (VAS) Baseline, week 12
VAY736 Serum Concentration - AUCinf 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - AUClast 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - CL 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Cmax 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - T1/2 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Tmax 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
VAY736 Serum Concentration - Vz 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks.
Einschreibung 27
Bedingung
Intervention

Interventionsart: Drug

Interventionsname: VAY736

Interventionsart: Drug

Interventionsname: Placebo

Armgruppenetikett: Placebo

Teilnahmeberechtigung

Kriterien:

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

Geschlecht: All

Mindestalter: 18 Years

Maximales Alter: 75 Years

Gesunde Freiwillige: No

Insgesamt offiziell
Nachname Rolle Zugehörigkeit
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Ort
Einrichtung: Novartis Investigative Site
Standort Länder

Germany

Überprüfungsdatum

January 2019

Verantwortliche Partei

Art: Sponsor

Schlüsselwörter
Hat den Zugriff erweitert No
Bedingung Durchsuchen
Anzahl der Waffen 3
Armgruppe

Etikette: VAY736 3 mg/kg

Art: Experimental

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

Etikette: VAY736 10 mg/kg

Art: Experimental

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

Etikette: Placebo

Art: Placebo Comparator

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

Akronym CVAY736X2201
Studiendesign Info

Zuweisung: Randomized

Interventionsmodell: Parallel Assignment

Hauptzweck: Treatment

Maskierung: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Maskierungsbeschreibung: 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).

Quelle: ClinicalTrials.gov