Clinical trial NCT02756650: 1 Year of Treatment With Canakinumab in Behçet's Disease Patients With Neurologic or Vascular Involvement
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Behcet Disease
Keywords: Behcet Disease
Inflammation
Immune system
Arthritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-04-29
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Attacks
timeFrame: 30 days
measure: Modified Expanded Disability Status Scale (EDSS)
timeFrame: 30 days
measure: Neuro-Behçet's Disability Score (NBDS)
timeFrame: 30 days
measure: Modified Ranking Score (mRS)
timeFrame: 30 days
measure: Ataxia
timeFrame: 30 days
measure: Physical Examination Scores Indicating Change in Muscle Strength
timeFrame: 30 days
measure: C-reactive Protein (CRP) Values
timeFrame: 30 days
measure: Erythrocyte Sedimentation Rate (ESR)
timeFrame: 30 days
measure: SAA (Serum Amyloid A)
timeFrame: 30 days
measure: Hemoptysis
timeFrame: 30 days
measure: Visual Analogue Scores (VAS) for Headache
timeFrame: 30 days
measure: Visual Analogue Scores (VAS) for Stomachache
timeFrame: 30 days
measure: Visual Analogue Scores (VAS) for Extremity Assessments
timeFrame: 30 days
measure: Visual Analogue Scores (VAS) for Patients' General Assessments
timeFrame: 30 days
measure: Physician's Global Assessment
timeFrame: 30 days
measure: Steroid Dose Regimen
timeFrame: 30 days
measure: BDCAF (Behçet's Disease Current Activity Form)
timeFrame: 30 days
measure: Extremity (Localized) Pain Assessment (VAS)
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
Locations:
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: IU Faculty of Medicine
name: Ahmet Gül, Prof
role: STUDY_CHAIR
affiliation: IU Faculty of Medicine
name: Murat Kurtuncu, Ass.Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Bilim University Faculty of Medicine
name: Gulsen Akman Demir, Prof
role: PRINCIPAL_INVESTIGATOR
References: