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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02756650
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 31.3
• Patients Per Site Per Month: 0.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Behcet Disease	Drug: Canakinumab	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Jun 23, 2016
• Actual Primary Completion Date: Jan 31, 2019
• Actual Study Completion Date: Jan 31, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Attacks [30 days]

   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.

2. Modified Expanded Disability Status Scale (EDSS) [30 days]

   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.

3. Neuro-Behçet's Disability Score (NBDS) [30 days]

   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.

4. Modified Ranking Score (mRS) [30 days]

   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.

5. Ataxia [30 days]

   Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.

6. Physical Examination Scores Indicating Change in Muscle Strength [30 days]

   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.

7. C-reactive Protein (CRP) Values [30 days]

   Mean CRP (C-reactive protein) value (8 participants)

8. Erythrocyte Sedimentation Rate (ESR) [30 days]

   Mean erythrocyte sedimentation rate (ESR) value (8 participants)

9. SAA (Serum Amyloid A) [30 days]

   Mean Serum Amyloid A value (8 participants)

10. Hemoptysis [30 days]

    The number of the participants with hemoptysis

11. Visual Analogue Scores (VAS) for Headache [30 days]

    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.

12. Visual Analogue Scores (VAS) for Stomachache [30 days]

    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.

13. Visual Analogue Scores (VAS) for Extremity Assessments [30 days]

    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.

14. Visual Analogue Scores (VAS) for Patients' General Assessments [30 days]

    Participants assessed their own well-being with VAS (visual analogue scale). Score 0 means the best outcome, score 10 is the worst outcome.

15. Physician's Global Assessment [30 days]

    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

16. Steroid Dose Regimen [30 days]

    Mean steroid treatment dose (8 participants)

17. BDCAF (Behçet's Disease Current Activity Form) [30 days]

    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.

18. Extremity (Localized) Pain Assessment (VAS) [30 days]

    Localized pain in the extremities were assessed by visual analogue scale scores ranging between Scale; 0 is the best outcome; 10 is worst.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Istanbul		Turkey	34093

Sponsors and Collaborators

• 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 Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 15, 2016

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02756650
• Other Study ID Numbers: CACZ885NTR01
• First Posted: Apr 29, 2016
• Last Update Posted: Jun 11, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Behcet Disease; Inflammation; Immune system; Arthritis
• Additional relevant MeSH terms: Behcet Syndrome

Study Results

Participant Flow

Recruitment Details	8 subjects enrolled 5 subjects were evaluated in Rheumatology clinic. 3 subjects were evaluated in Neurology clinic.
Pre-assignment Detail	Ten patients were planned to be enrolled. Nine patients were screened. Eight patients were enrolled. Six patients completed the study. One patient was dropped out in the 7th visit because of an unknown drug abuse. One patient was dropped out in the 11th visit because of adverse event, worsening in pulmonary artery aneurysm.

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Period Title: Overall Study
STARTED	8
COMPLETED	6
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.25 (2.320)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) population: all 8 subjects who took at least one dose of study medication

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Count of Participants [Participants]	0 0%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Behçet's Disease set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	3
Mean (Standard Deviation) [scores on a scale]	1.16 (2.02)

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Behçet's disease set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	3
Mean (Standard Deviation) [scores on a scale]	0.66 (1.15)

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Behçet's disease set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	3
Mean (Standard Deviation) [scores on a scale]	0.66 (1.15)

5. Primary Outcome

Title	Ataxia
Description	Number of the partcipants with ataxia. 3 participants from neurology clinic were evaluated.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	3
Count of Participants [Participants]	1 12.5%

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Behçet's disease set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	3
Upper right extremity	5.0 (0)
Lower right extremity	5.0 (0)
Upper left extremity	4.7 (0.57)
Lower left extremity	5.0 (0)

7. Primary Outcome

Title	C-reactive Protein (CRP) Values
Description	Mean CRP (C-reactive protein) value (8 participants)
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [mg/L]	14.58 (20.26)

8. Primary Outcome

Title	Erythrocyte Sedimentation Rate (ESR)
Description	Mean erythrocyte sedimentation rate (ESR) value (8 participants)
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [mm/H]	17.5 (12.77)

9. Primary Outcome

Title	SAA (Serum Amyloid A)
Description	Mean Serum Amyloid A value (8 participants)
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [mg/L]	78.66 (108.17)

10. Primary Outcome

Title	Hemoptysis
Description	The number of the participants with hemoptysis
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Count of Participants [Participants]	1 12.5%

11. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
VAS by participants	0.27 (0.32)
VAS by Physicians	0.2 (0.18)

12. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
VAS by participants	0.27 (0.32)
VAS by physicians	0.18 (0.17)

13. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
VAS by participants	1.07 (1.13)
VAS by physicians	0.87 (0.98)

14. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [scores on a scale]	1.72 (1.36)

15. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [scores on a scale]	3.75 (0.46)

16. Primary Outcome

Title	Steroid Dose Regimen
Description	Mean steroid treatment dose (8 participants)
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [mg/day]	9.5 (2.73)

17. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [scores]	1.62 (1.5)

18. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

randomized set

Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
Measure Participants	8
Mean (Standard Deviation) [scores on a scale]	1.28 (1.22)

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment
Adverse Event Reporting Description	An AE is any sign or symptom that occurs during the study treatment plus the # days post treatment
Arm/Group Title	ACZ885N
Arm/Group Description	Canakinumab
All Cause Mortality
	ACZ885N
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	ACZ885N
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	ACZ885N
	Affected / at Risk (%)	# Events
Total	8/8 (100%)
Ear and labyrinth disorders
Middle ear inflammation	1/8 (12.5%)
Eye disorders
Swelling of eyelid	1/8 (12.5%)
Gastrointestinal disorders
Abdominal pain upper	1/8 (12.5%)
Aphthous ulcer	7/8 (87.5%)
Gastrooesophageal reflux disease	1/8 (12.5%)
Infections and infestations
Folliculitis	3/8 (37.5%)
Influenza	1/8 (12.5%)
Pilonidal cyst	1/8 (12.5%)
Rash pustular	1/8 (12.5%)
Rhinitis	1/8 (12.5%)
Tonsillitis	1/8 (12.5%)
Investigations
Alanine aminotransferase increased	1/8 (12.5%)
Aspartate aminotransferase increased	1/8 (12.5%)
Hepatic enzyme increased	1/8 (12.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/8 (12.5%)
Nervous system disorders
Headache	2/8 (25%)
Nystagmus	1/8 (12.5%)
Tension headache	1/8 (12.5%)
Renal and urinary disorders
Haematuria	1/8 (12.5%)
Nephrolithiasis	1/8 (12.5%)
Reproductive system and breast disorders
Genital ulceration	1/8 (12.5%)
Testicular swelling	1/8 (12.5%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/8 (12.5%)
Oropharyngeal pain	1/8 (12.5%)
Pulmonary artery aneurysm	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Acne	2/8 (25%)
Erythema nodosum	1/8 (12.5%)
Vascular disorders
Thrombophlebitis superficial	3/8 (37.5%)

Limitations/Caveats

This was an exploratory trial that was not powered for a statistical analysis.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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