Title
1 Year of Treatment With Canakinumab in Behçet's Disease Patients With Neurologic or Vascular Involvement
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
Phase
Phase 2Lead Sponsor
NovartisStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Behcet DiseaseIntervention/Treatment
canakinumab ...Study Participants
8Primary 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.
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.
150 mg or 300 mg of canakinumab was administered monthly. IV (SC after month 6)
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
| Event Type | Organ System | Event Term | ACZ885N |
|---|
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.
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) 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.
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.
Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.
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.
Mean CRP (C-reactive protein) value (8 participants)
Mean erythrocyte sedimentation rate (ESR) value (8 participants)
Mean Serum Amyloid A value (8 participants)
The number of the participants with hemoptysis
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.
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.
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.
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 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
Mean steroid treatment dose (8 participants)
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.
Localized pain in the extremities were assessed by visual analogue scale scores ranging between Scale; 0 is the best outcome; 10 is worst.
