A Study to Assess the Effect of a Single Infusion of VAY736 on Disease Activity in Patients With Relapsing-remitting Multiple Sclerosis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02038049
• Collaborator: (none)
• Enrollment: 8
• Locations: 5
• Arms: 2
• Actual Duration (Months): 56.8
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This was a randomized, partially blinded, placebo-controlled, non-confirmatory study to assess the effects of a single infusion of VAY736 on disease activity as measured by brain MRI scans in patients with relapsing-remitting multiple sclerosis (RRMS).

Condition or Disease	Intervention/Treatment	Phase
Relapse Remitting Multiple Sclerosis	Drug: VAY736; Drug: Placebo	Phase 2

Detailed Description

The study was planned to be conducted in approximately 96 patients. However, after enrolling 8 patients, the recruitment was terminated based on strategic considerations.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Partially Blind, Placebo-controlled, Proof-of-concept Study to Assess the Effect of a Single Infusion of VAY736 on Disease Activity as Measured by Brain MRI Scans in Patients With Relapsing-remitting Multiple Sclerosis
• Actual Study Start Date: Dec 20, 2013
• Actual Primary Completion Date: May 5, 2015
• Actual Study Completion Date: Sep 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VAY736 Intravenous infusion of VAY736	Drug: VAY736; Single intravenous infusion of VAY736 (10 mg/kg); Other Names: Lanalumab
Placebo Comparator: Placebo to VAY736 Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16	Drug: Placebo; Placebo to VAY736

Outcome Measures

Primary Outcome Measures

1. Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 8, 12 and 16 [Week 8, Week 12, Week 16]

   The effect of VAY736, compared to placebo on the cumulative number of new gadolinium [Gd]-enhancing lesions on T1-weighted brain MRI scans in relapsing-remitting multiple sclerosis (RRMS) patient population at weeks 8, 12 and 16. Only descriptive statistics performed.

Secondary Outcome Measures

1. Number of All T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16 [Week 4, Week 8, Week 12, Week 16]

   Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess all T1-weighted Gadolinium (Gd) enhancing lesions. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.

2. Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16 [Week 4, Week 8, Week 12, Week 16]

   Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess all new T1-weighted Gadolinium (Gd) enhancing lesions. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.

3. Number of New or Enlarging T2-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16 [Week 4, Week 8, Week 12, Week 16]

   Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess T2 hyperintense lesions (new or enlarging T2-weighted lesions). Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.

4. T2 Burden of Disease (Total Volume of T2-weighted Lesions) at Weeks 4, 8, 12 and 16. [Week 4, Week 8, Week 12, Week 16]

   Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess T2 burden of disease. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.

5. Number of Subjects Without Any New MRI Disease Activity at Weeks 4, 8, 12 and 16. [Week 4, Week 8, Week 12, Week 16]

   Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess patients without any new MRI disease activity (no new Gd-enhancing lesions nor new or enlarging T2 lesions). Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.

6. Proportion of Relapse-free Patients Over the 16 Weeks of the Treatment Period. [Week 0 (Day 1), Week 4, Week 8, Week 12, Week 16]

   A relapse is defined as the appearance of a new neurological abnormality, or worsening of previously stable, or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5 C) or infection. A relapse was considered confirmed when confirmed by an Extended disability status scale (EDSS)-certified physician who was not involved in the treatment of the patient, was blinded to treatment allocation, and had no access to patient medical records. It was recommended that this occurs within 5 days of the onset of symptoms. A relapse was confirmed when it was accompanied by an increase of at least half a point (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Only descriptive statistics performed.

7. Number of Participants With On-Treatment Adverse Events, Serious Adverse Event, and Death [From first dosing (single administration, Day 1) up to End of Study Visit (EOS) depending on B cell recovery (ranging from week 48 to 216)]

   Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that VAY736 is safe for the treatment of patients with relapsing-remitting multiple sclerosis through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive statistics performed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key inclusion criteria:

• Male and female patients aged 18 to 55 years.

• Diagnosis of MS as defined by the 2010 revised McDonald criteria (Polman et al 2011).

• A relapsing-remitting course of disease with:

• at least 1 documented relapse during the previous 12 months (but not within 30 days prior to randomization ), or

• a positive Gd-enhancing lesion on brain MRI scan at screening.

• An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at screening.

• No evidence of a relapse within 30 days prior to randomization.

Key exclusion criteria:

• A manifestation of another type of MS other than RRMS.

• Findings on screening or baseline brain MRI inconsistent with the diagnosis of MS.

• History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome.

• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.

• Women of child-bearing potential and Pregnant or nursing (lactating) women.

• Screening CBC (complete blood count) laboratory values as follows:

• Hemoglobin levels below 10.0 g/dL

• Total leukocyte count less than 3,000 cells/µL

• Neutropenia, defined as absolute neutrophil counts less than 1500 cells/mm3

• Platelets less than 100,000/µL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Long Beach	California	United States	90806
2	Novartis Investigative Site	San Diego	California	United States	92103
3	Novartis Investigative Site	Hradec Kralove		Czechia	501 03
4	Novartis Investigative Site	Kharkiv		Ukraine	61068
5	Novartis Investigative Site	Lviv		Ukraine	79010

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02038049
• Other Study ID Numbers: CVAY736X2202; 2013-002324-16
• First Posted: Jan 16, 2014
• Last Update Posted: Jan 5, 2021
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Multiple Sclerosis; Relapsing-Remitting Multiple Sclerosis; Magnetic Resonance Imaging; VAY736; Lanalumab; monoclonal antibody; gadolinium [Gd]-enhancing lesions; B-Cell
• Additional relevant MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis

Study Results

Participant Flow

Recruitment Details	This study was conducted in 5 centers in 3 countries: Czech Republic (1), Ukraine (2 sites) and USA (2 sites).
Pre-assignment Detail	The study was planned to be conducted in approximately 96 patients. However, after enrolling 8 patients, the recruitment was terminated based on strategic considerations.

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Period Title: Overall Study
STARTED	4	4
Pharmacodynamic (PD) Analysis Set	4	4
COMPLETED	3	4
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	VAY736	Placebo to VAY736	Total
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.	Total of all reporting groups
Overall Participants	4	4	8
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	32.0 (10.42)	42.0 (2.45)	37.0 (8.82)
Sex: Female, Male (Count of Participants)
Female	2 50%	3 75%	5 62.5%
Male	2 50%	1 25%	3 37.5%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	3 75%	4 100%	7 87.5%
Other	1 25%	0 0%	1 12.5%

Outcome Measures

1. Primary Outcome

Title	Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 8, 12 and 16
Description	The effect of VAY736, compared to placebo on the cumulative number of new gadolinium [Gd]-enhancing lesions on T1-weighted brain MRI scans in relapsing-remitting multiple sclerosis (RRMS) patient population at weeks 8, 12 and 16. Only descriptive statistics performed.
Time Frame	Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Week 8	5	1
Week12	5	2
Week 16	6	3

2. Secondary Outcome

Title	Number of All T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16
Description	Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess all T1-weighted Gadolinium (Gd) enhancing lesions. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
Time Frame	Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Week 4	19	2
Week 8	20	2
Week 12	20	3
Week 16	21	4

3. Secondary Outcome

Title	Number of New T1-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16
Description	Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess all new T1-weighted Gadolinium (Gd) enhancing lesions. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
Time Frame	Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Week 4	4	1
Week 8	1	0
Week 12	0	1
Week 16	1	1

4. Secondary Outcome

Title	Number of New or Enlarging T2-weighted Gadolinium (Gd)-Enhancing Lesions at Weeks 4, 8, 12 and 16
Description	Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess T2 hyperintense lesions (new or enlarging T2-weighted lesions). Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
Time Frame	Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Week 4	279	94
Week 8	277	93
Week 12	276	91
Week 16	264	91

5. Secondary Outcome

Title	T2 Burden of Disease (Total Volume of T2-weighted Lesions) at Weeks 4, 8, 12 and 16.
Description	Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess T2 burden of disease. Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
Time Frame	Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Week 4	20108.9	17706
Week 8	18998.9	16785
Week 12	18484.1	15996
Week 16	18102.7	17919

6. Secondary Outcome

Title	Number of Subjects Without Any New MRI Disease Activity at Weeks 4, 8, 12 and 16.
Description	Magnetic resonance imaging (MRI) scanning of the brain was performed at screening/baseline, week 4, week 8, week 12 and week 16 to assess patients without any new MRI disease activity (no new Gd-enhancing lesions nor new or enlarging T2 lesions). Each MRI scan was reviewed by a local neuro-radiologist. Only descriptive statistics performed.
Time Frame	Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Week 4	4 100%	2 50%
Week 8	1 25%	0 0%
Week 12	0 0%	1 25%
Week 16	3 75%	3 75%

7. Secondary Outcome

Title	Proportion of Relapse-free Patients Over the 16 Weeks of the Treatment Period.
Description	A relapse is defined as the appearance of a new neurological abnormality, or worsening of previously stable, or improving pre-existing neurological abnormality, separated by at least 30 days from the onset of a preceding clinical demyelinating event. The abnormality must be present for at least 24 hours and occur in the absence of fever (<37.5 C) or infection. A relapse was considered confirmed when confirmed by an Extended disability status scale (EDSS)-certified physician who was not involved in the treatment of the patient, was blinded to treatment allocation, and had no access to patient medical records. It was recommended that this occurs within 5 days of the onset of symptoms. A relapse was confirmed when it was accompanied by an increase of at least half a point (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the EDSS or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS). Only descriptive statistics performed.
Time Frame	Week 0 (Day 1), Week 4, Week 8, Week 12, Week 16

Outcome Measure Data

Analysis Population Description

Pharmacodynamic (PD) analysis set, which consisted of all patients who received at least one dose of study drug during the treatment and one evaluable PD assessment, was considered

Arm/Group Title	VAY736	Placebo to VAY736
Arm/Group Description	Intravenous infusion of VAY736	Matching placebo (infusion bag) administered intravenously. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4
Relapse-free	4 100%	4 100%
Relapse	0 0%	0 0%
Relapse-free	4 100%	4 100%
Relapse	0 0%	0 0%
Relapse-free	4 100%	4 100%
Relapse	0 0%	0 0%
Relapse-free	4 100%	4 100%
Relapse	0 0%	0 0%
Relapse-free	3 75%	3 75%
Relapse	1 25%	1 25%

8. Secondary Outcome

Title	Number of Participants With On-Treatment Adverse Events, Serious Adverse Event, and Death
Description	Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC) to demonstrate that VAY736 is safe for the treatment of patients with relapsing-remitting multiple sclerosis through the monitoring of relevant clinical and laboratory safety parameters. Only descriptive statistics performed.
Time Frame	From first dosing (single administration, Day 1) up to End of Study Visit (EOS) depending on B cell recovery (ranging from week 48 to 216)

Outcome Measure Data

Analysis Population Description

The Safety Set, which consisted of all patients who received at least one dose of study drug during the treatment period, was considered

Arm/Group Title	VAY736 Administered at Visit 2 (Day 1)	VAY736 Administered at Visit 7 (Week 16 - Week 17)	Placebo Administered at Visit 2
Arm/Group Description	Intravenous infusion of VAY736 at Visit 2 (Day 1)	Intravenous infusion of VAY736 at Visit 7 (Week 16 - Week 17)	Matching placebo (infusion bag) administered intravenously at Visit 2. Placebo randomized patients were offered optional VAY736 administration after week 16.
Measure Participants	4	4	4
On-treatment Adverse Events (AEs)	4 100%	3 75%	1 12.5%
On-treatment Serious Adverse Events (SAEs)	0 0%	0 0%	0 0%
On-treatment Deaths	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Adverse events and serious adverse events were collected from first dosing (single administration, Day 1) up to End of Study Visit (EOS) depending on B cell recovery (ranging from week 48 to 216).
Arm/Group Title	VAY736 Administered at Visit 2 (Day 1)		VAY736 Administered at Visit 7 (Week 16 - Week 17)		Placebo Administered at Visit 2
Arm/Group Description	Intravenous infusion of VAY736 at Visit 2 (Day 1)		Intravenous infusion of VAY736 at Visit 7 (Week 16 - Week 17)		Matching placebo (infusion bag) administered intravenously at Visit 2. Placebo randomized patients were offered optional VAY736 administration after week 16.
All Cause Mortality
	VAY736 Administered at Visit 2 (Day 1)		VAY736 Administered at Visit 7 (Week 16 - Week 17)		Placebo Administered at Visit 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		0/4 (0%)
Serious Adverse Events
	VAY736 Administered at Visit 2 (Day 1)		VAY736 Administered at Visit 7 (Week 16 - Week 17)		Placebo Administered at Visit 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/4 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	VAY736 Administered at Visit 2 (Day 1)		VAY736 Administered at Visit 7 (Week 16 - Week 17)		Placebo Administered at Visit 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		3/4 (75%)		1/4 (25%)
Blood and lymphatic system disorders
Lymphopenia	0/4 (0%)		1/4 (25%)		0/4 (0%)
Cardiac disorders
Palpitations	1/4 (25%)		0/4 (0%)		0/4 (0%)
Tachycardia	3/4 (75%)		0/4 (0%)		0/4 (0%)
Gastrointestinal disorders
Nausea	3/4 (75%)		1/4 (25%)		0/4 (0%)
Vomiting	1/4 (25%)		0/4 (0%)		0/4 (0%)
General disorders
Asthenia	2/4 (50%)		0/4 (0%)		0/4 (0%)
Chills	2/4 (50%)		0/4 (0%)		0/4 (0%)
Hyperthermia	1/4 (25%)		0/4 (0%)		0/4 (0%)
Pyrexia	1/4 (25%)		1/4 (25%)		0/4 (0%)
Infections and infestations
Respiratory tract infection viral	1/4 (25%)		0/4 (0%)		0/4 (0%)
Rhinitis	0/4 (0%)		1/4 (25%)		0/4 (0%)
Upper respiratory tract infection	0/4 (0%)		1/4 (25%)		0/4 (0%)
Injury, poisoning and procedural complications
Infusion related reaction	0/4 (0%)		1/4 (25%)		0/4 (0%)
Road traffic accident	1/4 (25%)		0/4 (0%)		0/4 (0%)
Investigations
Glucose urine present	0/4 (0%)		1/4 (25%)		0/4 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/4 (25%)		0/4 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/4 (25%)		0/4 (0%)		0/4 (0%)
Back pain	1/4 (25%)		0/4 (0%)		0/4 (0%)
Musculoskeletal pain	1/4 (25%)		0/4 (0%)		0/4 (0%)
Nervous system disorders
Headache	3/4 (75%)		1/4 (25%)		1/4 (25%)
Hypotonia	1/4 (25%)		0/4 (0%)		0/4 (0%)
Somnolence	1/4 (25%)		0/4 (0%)		0/4 (0%)
Psychiatric disorders
Anxiety	1/4 (25%)		0/4 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/4 (25%)		0/4 (0%)		0/4 (0%)
Nasal congestion	1/4 (25%)		0/4 (0%)		0/4 (0%)
Rhinorrhoea	1/4 (25%)		0/4 (0%)		0/4 (0%)

Limitations/Caveats

After enrolling 8 patients, the recruitment was terminated based on strategic considerations.

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.