Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2013-000250-22 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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
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:
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VAY736 3 mg/kg | Experimental | single dose iv of VAY736 at a dose of 3mg/kg |
|
| VAY736 10 mg/kg | Experimental | single dose iv of VAY736 at a dose of 10mg/kg |
|
| Placebo | Placebo Comparator | single dose iv of Placebo. At Week 24 patients were offered to receive open label VAY736 10 mg/kg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VAY736 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, week 12 |
| Overall Incidence of Adverse Events | Number of subjects with Adverse Events during the double blind treatment period. | Baseline to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
INCLUSION CRITERIA:
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
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Berlin | 10117 | Germany |
Not provided
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicaltrials.com | View source |
Not provided
The patients were enrolled in 2 sequential cohorts:
Cohort 1: Six patients were randomized to receive a single dose iv of VAY736 at a dose of 3mg/kg or placebo at a 2:1 ratio.
Cohort 2: Twenty one patients were randomized to receive a single iv dose of VAY736 at a dose of 10.0 mg/kg or 3.0 mg/kg or placebo at a 6:1:3 ratio.
A total of 27 patients were enrolled and randomized into the study at one site in Germany.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | single dose iv of Placebo (+ Option to receive Open label VAY736 10 mg/kg at Week 24) |
| FG001 | VAY736 3 mg/kg | single dose iv of VAY736 at a dose of 3mg/kg |
| FG002 | VAY736 10 mg/kg | single dose iv of VAY736 at a dose of 10mg/kg |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Core Study |
|
| |||||||||||||||||||||||||||
| Open Label VAY736 10 mg/kg Extension |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | single dose iv of Placebo |
| BG001 | VAY736 3 mg/kg | single dose iv of VAY736 at a dose of 3mg/kg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | PD analysis set | Posted | Mean | Standard Deviation | units on a scale | Baseline, week 12 |
|
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).
All AEs were reported until week 52. After week 52 only AEs related to VAY736 and AEs related to infection, potential malignant events and neutropenia were recorded.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Colitis | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (20.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 31, 2016 | Jan 23, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 11, 2017 | Jan 23, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C000656267 | ianalumab |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
|
| 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. | 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. | 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). | 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). | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
| NOT COMPLETED |
|
|
| BG002 |
| VAY736 10 mg/kg |
single dose iv of VAY736 at a dose of 10mg/kg |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| VAY736 3 mg/kg |
single dose iv of VAY736 at a dose of 3mg/kg |
| OG002 | VAY736 10 mg/kg | single dose iv of VAY736 at a dose of 10mg/kg |
| OG003 | VAY736 Combined | Combining VAY736 3mg/kg and VAY736 10mg/kg |
|
|
|
| Secondary | 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. | PD analysis set | Posted | Mean | Standard Deviation | units on a scale | Baseline, week 12 |
|
|
|
| Secondary | 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. | PD analysis set | Posted | Mean | Standard Deviation | units on a scale | Baseline, week 12 |
|
|
|
| Secondary | 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. | PD analysis set | Posted | Mean | Standard Deviation | units on a scale | Baseline, week 12 |
|
|
|
| Secondary | 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). | PD analysis set | Posted | Mean | Standard Deviation | units on a scale | Baseline, week 12 |
|
|
|
| Secondary | 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). | PD analysis set | Posted | Mean | Standard Deviation | units on a scale | Baseline, week 12 |
|
|
|
| Secondary | 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. | PK analysis set | Posted | Median | Full Range | day*ug/mL | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Secondary | 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. | PK analysis set | Posted | Median | Full Range | day*ug/mL | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Secondary | 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. | PK analysis set | Posted | Median | Full Range | L/day | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Secondary | VAY736 Serum Concentration - Cmax | The observed maximum serum concentration following drug administration [mass / volume]. The concentration of VAY736 was measured in the serum. | PK analysis set | Posted | Median | Full Range | ug/mL | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Secondary | 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. | PK analysis set | Posted | Median | Full Range | days | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Secondary | VAY736 Serum Concentration - Tmax | The time to reach the maximum concentration after drug administration [time]. The concentration of VAY736 was measured in the serum. | PK analysis set | Posted | Median | Full Range | hours | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Secondary | 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. | PK analysis set | Posted | Median | Full Range | L | 0, 1, 2, 3, 6, 9, 12, 16, 20, 24 and approximately 52 weeks. |
|
|
|
| Primary | Overall Incidence of Adverse Events | Number of subjects with Adverse Events during the double blind treatment period. | Safety analysis set | Posted | Count of Participants | Participants | Baseline to Week 24 |
|
|
|
| 9 |
| 1 |
| 9 |
| 9 |
| 9 |
| EG001 | VAY736 3mg/kg | VAY736 3mg/kg | 0 | 6 | 2 | 6 | 6 | 6 |
| EG002 | VAY736 10mg/kg | VAY736 10mg/kg | 0 | 12 | 0 | 12 | 11 | 12 |
| EG003 | Open Label VAY736 10mg/kg | Open label VAY736 10mg/kg | 0 | 5 | 1 | 5 | 5 | 5 |
| Inguinal hernia | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Jaw fracture | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Ovarian cyst torsion | Reproductive system and breast disorders | MedDRA (20.1) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA (20.1) | Systematic Assessment |
|
| Chalazion | Eye disorders | MedDRA (20.1) | Systematic Assessment |
|
| Keratitis | Eye disorders | MedDRA (20.1) | Systematic Assessment |
|
| Vitreous detachment | Eye disorders | MedDRA (20.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Auriculotemporal syndrome | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Noninfective sialoadenitis | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA (20.1) | Systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (20.1) | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Gastrointestinal infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Urogenital infection bacterial | Infections and infestations | MedDRA (20.1) | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Ligament rupture | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Sjogren's syndrome | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Synovitis | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (20.1) | Systematic Assessment |
|
| Postmenopausal haemorrhage | Reproductive system and breast disorders | MedDRA (20.1) | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (20.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
|
| Change from Baseline to Week 12 |
|
|
| Physical component score: Change from Baseline |
|
| Mental component score: Baseline |
|
| Mental component score: Week 12 |
|
| Mental component score: Change from Baseline |
|
|
| General Fatigue: Change from Baseline |
|
| Physical Fatigue: Baseline |
|
| Physical Fatigue: Week 12 |
|
| Physical Fatigue: Change from Baseline |
|
| Mental Fatigue: Baseline |
|
| Mental Fatigue: Week 12 |
|
| Mental Fatigue: Change from Baseline |
|
| Reduced motivation: Baseline |
|
| Reduced motivation: Week 12 |
|
| Reduced motivation: Change from Baseline |
|
| Reduced activity: Baseline |
|
| Reduced activity: Week 12 |
|
| Reduced activity: Change from Baseline |
|
|
| Change from Baseline to Week 12 |
|
|
| Change from Baseline to Week 12 |
|
| Subjects with AEs within 24hr of infusion |
|
| Subjects with AEs post 24hr of infusion |
|
| Subjects with Study drug-related AEs |
|
| Subjects with Infusion related AEs |
|