1 Year of Treatment With Canakinumab in Behçet's Disease Patients With Neurologic or Vascular Involvement (Behcet)
Primary Purpose
Behcet Disease
Status
Completed
Phase
Phase 2
Locations
Turkey
Study Type
Interventional
Intervention
Canakinumab
Sponsored by
About this trial
This is an interventional treatment trial for Behcet Disease focused on measuring Behcet Disease, Inflammation, Immune system, Arthritis
Eligibility Criteria
Inclusion Criteria:
Patients aged over 18-60 Behced Disease fulfilling the International Study Group (ISG) criteria, who have a recent exacerbation of large-vessel vascular disease and/or parenchymal neurologic disease For Neurologic Involvement
- Patients experiencing an acute exacerbation of parenchymal neurologic disease involving brainstem and/or diencephalic region.
- Exacerbation is defined based on the presence of both of the following:
- An acute/subacute neurological syndrome including any of hemiparesis, ataxia, dysarthria,headache within the first month of onset of neurologic manifestations (without any prior high dose steroid treatment)
- Compatible cranial MRI lesion involving brainstem and/or diencephalic region
For Vascular Disease :
Patients experiencing an acute exacerbation of vascular disease within the last month, involving
- Large arteries (abdominal aorta, pulmonary arteries, extremity arteries)
- Large veins (deep vein thrombosis of extremities, caval vein thrombosis, dural sinus thrombosis)
- Compatible radiological findings (spiral CT, MR, or Doppler ultrasonography)
Exclusion Criteria:
For Neurologic Involvement :
- Presence of severe neurological sequelae from any previous attacks rendering the patient dependent on others physically or mentally
- Any other neurological cause underlying the picture including ischemic central nervous system lesion on MRI
- Any previous treatment with biological agents other than interferon-alpha or any previous treatment with cyclophosphamide
- No interferon in the last 6 months, no Intra Venous Metilprednizolon in the past month
For Vascular disease and general :
- Presence of severe vascular sequelae from any previous attacks rendering the patient dependent on others
- Any other vascular disease complication the evaluation of exacerbation
- Any previous treatment with biological agents other than interferon alpha, or any previous treatment with cyclophosphamide
- No interferon alpha in the last 6 months, no IVMP in the past month
- History of Squamo Cell Carcinoma OR Basal Cell Carcinoma in previous 5 years. General
- Presence or history of any other inflammatory rheumatic disease
- Positive Purified Protein Derivative test (according to local guidance) where an active Tuberculosis infection cannot be excluded via Quantiferon (T-Spot or radiographic imaging if needed) Pregnancy or lactation
- Presence of any active or chronic infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to screening
- History or a malignancy within the last 5 years, except for successfully excised squamous or basal cell carcinoma of the skin
- Women of childbearing potential not using the contraception method(s) specified in this study, as well as women who are breastfeeding
- With known sensitivity to canakinumab
- Use of any other investigational agent in the last 30 days
Sites / Locations
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Canakinumab
Arm Description
Canakinumab was administered monthly
Outcomes
Primary Outcome Measures
Number of Participants With Attacks
Resolution of acute exacerbation findings related to Behçet's Disease (BD). The attacks were assessed by pyhsician global assesment.
For patients with parenchymal neurologic disease: Resolution of acute exacerbation of parenchymal neurologic findings based on improvements in any of the following items without deterioration on Day 30
This was an exploratory trial that was not powered for a statistical analysis.
Modified Expanded Disability Status Scale (EDSS)
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. Scale range is between 0-10 with 10 being most disability. Mean score of 3 participants who were evaluated in Neurology clinic. Other 5 participants were not evaluated for EDSS.
Neuro-Behçet's Disability Score (NBDS)
Neuro-Behçet's disability score (NBDS) has been proposed for parenchymal-NBD patients to quantify disabilities. This comprises scores for motor and cognitive status. NBDS is the arithmetic sum of both scores and ranges from 0 to 8, with 8 being death due to NBD. 3 neurologic participants were evaluated.
Modified Ranking Score (mRS)
Mean Modified Rankin Scale (mRS): mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Scores range from 0-5 with 5 being the worst outcome. Only 3 participants from neurology clinic were evaluated with this scale.
Ataxia
Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.
Physical Examination Scores Indicating Change in Muscle Strength
All 4 extremties were evaluated for muscle strength (upper right, upper left, lower right and lower left) fro each patient. Score 0 is the worst outcome whereas 5 is the best outcome for muscle strength. 3 participants from neurology clinic were assessed.
C-reactive Protein (CRP) Values
Mean CRP (C-reactive protein) value (8 participants)
Erythrocyte Sedimentation Rate (ESR)
Mean erythrocyte sedimentation rate (ESR) value (8 participants)
SAA (Serum Amyloid A)
Mean Serum Amyloid A value (8 participants)
Hemoptysis
The number of the participants with hemoptysis
Visual Analogue Scores (VAS) for Headache
Headache intensity was measured by VAS where score 0 means "no pain," and score 10 means "the worst pain''. Physician and participant determined the VAS score separately.
Visual Analogue Scores (VAS) for Stomachache
Stomacheache intensity was measured by VAS where score 0 means "no pain," and score 10 means "the worst pain''. VAS is determined separately by physician and the participants.
Visual Analogue Scores (VAS) for Extremity Assessments
Extremity assessments were measured by VAS where score 0 means "no pain," and score 10 means "the worst possible pain''. The physicians and participants evaluated VAS separately.
Visual Analogue Scores (VAS) for Patients' General Assessments
Participants assessed their own well-being with VAS (visual analogue scale). Score 0 means the best outcome, score 10 is the worst outcome.
Physician's Global Assessment
Physician's General Assessments is VAS scale, ranging between 0-5, showing the disease status of participants. Score 0 is the worst outcome; 5 is the best outcome
Steroid Dose Regimen
Mean steroid treatment dose (8 participants)
BDCAF (Behçet's Disease Current Activity Form)
BDCAF is an assessment that is made by physician for evaluating the disease activity in last four weeks. Score range is 0 to 12, 0 is the best outcome, 12 is the worst outcome.
Extremity (Localized) Pain Assessment (VAS)
Localized pain in the extremities were assessed by visual analogue scale scores ranging between Scale; 0 is the best outcome; 10 is worst.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02756650
Brief Title
1 Year of Treatment With Canakinumab in Behçet's Disease Patients With Neurologic or Vascular Involvement
Acronym
Behcet
Official Title
An Open Label, Exploratory Study to Establish the Efficacy and Safety of 1 Year Canakinumab Treatment in Behçet's Disease Patients With Neurologic or Vascular Involvement
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
June 23, 2016 (Actual)
Primary Completion Date
January 31, 2019 (Actual)
Study Completion Date
January 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Primary objective of the study was to evaluate the safety and efficacy of canakinumab on the clinical and inflammatory findings of Behced Disease patients with neurologic and vascular involvement.
Detailed Description
Primary endpoint: Resolution of acute exacerbation findings related to Behçet's Disease (BD) based on achievements in any of the following items without deterioration on day 30:
For patients with parenchymal neurologic disease: Resolution of acute exacerbation of parenchymal neurologic findings based on improvements in any of the following items without deterioration on Day 30:
Improvement of muscle strength, ataxia, or other relevant neurologic findings depending on the involved region on neurological examination (by Neuro-Behçet's Disease Score, Modified Expanded Disability Status Scale, and Modified Rankin Scores) cerebrospinal fluid
Improvement in systemic inflammatory findings (CRP, Erythrocyte Sedimentation Rate , SAA)
Any decrease in the size of the MRI lesion, or disappearance of contrast enhancement
Improvement in patients' and physicians global assessment using a 10-cm visual analogue scale (VAS)
Complete response was defined as full clinical recovery to the pre-attack state, disappearance of MRI lesion(s), and normalisation of Cerebrospinal Fluid findings.
Partial response was defined as partial improvement in clinical findings, but with findings still worse than the pre-attack state, and MRI lesions, which become smaller with no or less enhancement, and a decrease in cerebrospinal fluid cell count.
Non-response was defined as no improvement in clinical findings, no change on MRI, no change in cerebrospinal fluid parameters, or worsening in those findings.
For patients with large vessel vascular disease: Resolution of acute vascular exacerbation findings related to Behçet's Disease based on achievements in any of the following items without deterioration at 1 month:
Improvement in relevant symptoms (localised pain, abdominal pain, calf thickness, haemoptysis) by using physician and patient's global assessment with VAS
Improvement in systemic inflammatory findings (CRP, ESR, SAA)
Any improvement in radiological findings depending on the involved vessels (MR, CT or Doppler findings)
Improvement in patients' and physicians global assessment using a 10-cm visual analogue scale (VAS)
Complete response was defined as clinical and laboratory improvement based on ≥50% improvements in patient's and physician's global assessments by using VAS, and ≥50% reduction in CRP values; along with stable or ≥20% reduced aneurysm size in patients with arterial involvement, and stable or ≥20% reduced calf swelling in patients with lower extremity venous thrombosis.
Partial response was defined as clinical and laboratory improvement based on observations of an improvement between 20-49% according to patient's and physician's global assessments by using VAS, 20-49% reduction in CRP values; along with stable or less than 20% reduced aneurysm size in patients with arterial involvement, and stable or less than 20% reduced calf swelling in patients with lower extremity thrombosis.
Non-response will be defined as observing no or less than 20% clinical improvement by patient's and physician's global VAS or worsening of clinical findings, no change or increase in acute phase response, increase in aneurysm size for patients with arterial involvement or progression of venous thrombosis in patients with venous involvement.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Behcet Disease
Keywords
Behcet Disease, Inflammation, Immune system, Arthritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Canakinumab
Arm Type
Experimental
Arm Description
Canakinumab was administered monthly
Intervention Type
Drug
Intervention Name(s)
Canakinumab
Other Intervention Name(s)
ACZ885
Intervention Description
150 mg or 300 mg of canakinumab was administered monthly. IV (SC after month 6)
Primary Outcome Measure Information:
Title
Number of Participants With Attacks
Description
Resolution of acute exacerbation findings related to Behçet's Disease (BD). The attacks were assessed by pyhsician global assesment.
For patients with parenchymal neurologic disease: Resolution of acute exacerbation of parenchymal neurologic findings based on improvements in any of the following items without deterioration on Day 30
This was an exploratory trial that was not powered for a statistical analysis.
Time Frame
30 days
Title
Modified Expanded Disability Status Scale (EDSS)
Description
The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability over time. It is widely used in clinical trials and in the assessment of people with MS. Scale range is between 0-10 with 10 being most disability. Mean score of 3 participants who were evaluated in Neurology clinic. Other 5 participants were not evaluated for EDSS.
Time Frame
30 days
Title
Neuro-Behçet's Disability Score (NBDS)
Description
Neuro-Behçet's disability score (NBDS) has been proposed for parenchymal-NBD patients to quantify disabilities. This comprises scores for motor and cognitive status. NBDS is the arithmetic sum of both scores and ranges from 0 to 8, with 8 being death due to NBD. 3 neurologic participants were evaluated.
Time Frame
30 days
Title
Modified Ranking Score (mRS)
Description
Mean Modified Rankin Scale (mRS): mRS is a scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. Scores range from 0-5 with 5 being the worst outcome. Only 3 participants from neurology clinic were evaluated with this scale.
Time Frame
30 days
Title
Ataxia
Description
Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.
Time Frame
30 days
Title
Physical Examination Scores Indicating Change in Muscle Strength
Description
All 4 extremties were evaluated for muscle strength (upper right, upper left, lower right and lower left) fro each patient. Score 0 is the worst outcome whereas 5 is the best outcome for muscle strength. 3 participants from neurology clinic were assessed.
Time Frame
30 days
Title
C-reactive Protein (CRP) Values
Description
Mean CRP (C-reactive protein) value (8 participants)
Time Frame
30 days
Title
Erythrocyte Sedimentation Rate (ESR)
Description
Mean erythrocyte sedimentation rate (ESR) value (8 participants)
Time Frame
30 days
Title
SAA (Serum Amyloid A)
Description
Mean Serum Amyloid A value (8 participants)
Time Frame
30 days
Title
Hemoptysis
Description
The number of the participants with hemoptysis
Time Frame
30 days
Title
Visual Analogue Scores (VAS) for Headache
Description
Headache intensity was measured by VAS where score 0 means "no pain," and score 10 means "the worst pain''. Physician and participant determined the VAS score separately.
Time Frame
30 days
Title
Visual Analogue Scores (VAS) for Stomachache
Description
Stomacheache intensity was measured by VAS where score 0 means "no pain," and score 10 means "the worst pain''. VAS is determined separately by physician and the participants.
Time Frame
30 days
Title
Visual Analogue Scores (VAS) for Extremity Assessments
Description
Extremity assessments were measured by VAS where score 0 means "no pain," and score 10 means "the worst possible pain''. The physicians and participants evaluated VAS separately.
Time Frame
30 days
Title
Visual Analogue Scores (VAS) for Patients' General Assessments
Description
Participants assessed their own well-being with VAS (visual analogue scale). Score 0 means the best outcome, score 10 is the worst outcome.
Time Frame
30 days
Title
Physician's Global Assessment
Description
Physician's General Assessments is VAS scale, ranging between 0-5, showing the disease status of participants. Score 0 is the worst outcome; 5 is the best outcome
Time Frame
30 days
Title
Steroid Dose Regimen
Description
Mean steroid treatment dose (8 participants)
Time Frame
30 days
Title
BDCAF (Behçet's Disease Current Activity Form)
Description
BDCAF is an assessment that is made by physician for evaluating the disease activity in last four weeks. Score range is 0 to 12, 0 is the best outcome, 12 is the worst outcome.
Time Frame
30 days
Title
Extremity (Localized) Pain Assessment (VAS)
Description
Localized pain in the extremities were assessed by visual analogue scale scores ranging between Scale; 0 is the best outcome; 10 is worst.
Time Frame
30 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients aged over 18-60 Behced Disease fulfilling the International Study Group (ISG) criteria, who have a recent exacerbation of large-vessel vascular disease and/or parenchymal neurologic disease For Neurologic Involvement
Patients experiencing an acute exacerbation of parenchymal neurologic disease involving brainstem and/or diencephalic region.
Exacerbation is defined based on the presence of both of the following:
An acute/subacute neurological syndrome including any of hemiparesis, ataxia, dysarthria,headache within the first month of onset of neurologic manifestations (without any prior high dose steroid treatment)
Compatible cranial MRI lesion involving brainstem and/or diencephalic region
For Vascular Disease :
Patients experiencing an acute exacerbation of vascular disease within the last month, involving
Large arteries (abdominal aorta, pulmonary arteries, extremity arteries)
Large veins (deep vein thrombosis of extremities, caval vein thrombosis, dural sinus thrombosis)
Compatible radiological findings (spiral CT, MR, or Doppler ultrasonography)
Exclusion Criteria:
For Neurologic Involvement :
Presence of severe neurological sequelae from any previous attacks rendering the patient dependent on others physically or mentally
Any other neurological cause underlying the picture including ischemic central nervous system lesion on MRI
Any previous treatment with biological agents other than interferon-alpha or any previous treatment with cyclophosphamide
No interferon in the last 6 months, no Intra Venous Metilprednizolon in the past month
For Vascular disease and general :
Presence of severe vascular sequelae from any previous attacks rendering the patient dependent on others
Any other vascular disease complication the evaluation of exacerbation
Any previous treatment with biological agents other than interferon alpha, or any previous treatment with cyclophosphamide
No interferon alpha in the last 6 months, no IVMP in the past month
History of Squamo Cell Carcinoma OR Basal Cell Carcinoma in previous 5 years. General
Presence or history of any other inflammatory rheumatic disease
Positive Purified Protein Derivative test (according to local guidance) where an active Tuberculosis infection cannot be excluded via Quantiferon (T-Spot or radiographic imaging if needed) Pregnancy or lactation
Presence of any active or chronic infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to screening
History or a malignancy within the last 5 years, except for successfully excised squamous or basal cell carcinoma of the skin
Women of childbearing potential not using the contraception method(s) specified in this study, as well as women who are breastfeeding
With known sensitivity to canakinumab
Use of any other investigational agent in the last 30 days
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmet Gül, Prof
Organizational Affiliation
IU Faculty of Medicine
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Murat Kurtuncu, Ass.Prof
Organizational Affiliation
IU Faculty of Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gulsen Akman Demir, Prof
Organizational Affiliation
Bilim University Faculty of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Novartis Investigative Site
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IPD Sharing Time Frame
The publication has been planned for Q4 2020.
IPD Sharing Access Criteria
Access from peer reviewed journal
Learn more about this trial
1 Year of Treatment With Canakinumab in Behçet's Disease Patients With Neurologic or Vascular Involvement
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