1 Year of Treatment With Canakinumab in Behçet's Disease Patients With Neurologic or Vascular Involvement (Behcet)

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

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.

Study Overview

• Status: Completed
• Conditions: Behcet Disease
• Intervention / Treatment: Drug: Canakinumab

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey, 34093
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Canakinumab; Canakinumab was administered monthly	Drug: Canakinumab; 150 mg or 300 mg of canakinumab was administered monthly. IV (SC after month 6); Other Names: ACZ885

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	30 days
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.	30 days
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.	30 days
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.	30 days
Ataxia	Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.	30 days
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.	30 days
C-reactive Protein (CRP) Values	Mean CRP (C-reactive protein) value (8 participants)	30 days
Erythrocyte Sedimentation Rate (ESR)	Mean erythrocyte sedimentation rate (ESR) value (8 participants)	30 days
SAA (Serum Amyloid A)	Mean Serum Amyloid A value (8 participants)	30 days
Hemoptysis	The number of the participants with hemoptysis	30 days
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.	30 days
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.	30 days
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.	30 days
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.	30 days
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	30 days
Steroid Dose Regimen	Mean steroid treatment dose (8 participants)	30 days
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.	30 days
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.	30 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Chair: Ahmet Gül, Prof, IU Faculty of Medicine; Principal Investigator: Murat Kurtuncu, Ass.Prof, IU Faculty of Medicine; Principal Investigator: Gulsen Akman Demir, Prof, Bilim University Faculty of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2016
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: March 31, 2016
• First Submitted That Met QC Criteria: April 26, 2016
• First Posted (Estimate): April 29, 2016

Study Record Updates

• Last Update Posted (Actual): June 11, 2020
• Last Update Submitted That Met QC Criteria: May 28, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Inflammation; Arthritis; Immune system; Behcet Disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Eye Diseases; Genetic Diseases, Inborn; Stomatognathic Diseases; Mouth Diseases; Uveitis, Anterior; Panuveitis; Uveitis; Uveal Diseases; Vasculitis; Hereditary Autoinflammatory Diseases; Skin Diseases, Genetic; Skin Diseases, Vascular; Behcet Syndrome
• Other Study ID Numbers: CACZ885NTR01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD 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
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No