Long-term, Open-label, Multicenter Study Assessing Long-term Cardiovascular Risks

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02232061
• Collaborator: (none)
• Enrollment: 6
• Locations: 4
• Arm: 1
• Actual Duration (Months): 63.8
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study will evaluate if patients who had a serious cardiovascular event upon initiation of fingolimod are at risk to delevop long term other cardiovascular events

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Fingolimod	Phase 4

Detailed Description

This was a multi-national, long-term safety study. Patients enrolled in study FTY720D2406 who experienced a cardiovascular event within 24-hours of fingolimod treatment initiation which led to overnight monitoring or met serious adverse event criteria, were eligible to participate in this study.

Patients who experienced a qualifying event in study CFTY720D2406 started study CFTY720D2409 approximately 6 months after the occurrence of the CFTY720D2406 qualifying event.

Patients underwent mandatory assessments on a 6-monthly basis including 12-lead ECG, vital signs. Other assessments were performed as per routine practice.

The primary objective of the study was to estimate the long-term cardiovascular risk of fingolimod in patients who experienced a cardiovascular event during treatment initiation.

The study has no stand-alone secondary objective. However data from the CFTY720D2409 and CFTY720D2406 studies will be pooled to supplement CFTY720DD2406 study and support its primary and secondary objectives of evaluating the safety profile of fingolimod.

The pooled data will be appended to this result upon completion of FDA submission.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Long-term, Open-label, Multicenter Study Assessing Long-term Cardiovascular Risks in Patients Treated With Fingolimod
• Actual Study Start Date: Sep 29, 2014
• Actual Primary Completion Date: Jan 24, 2020
• Actual Study Completion Date: Jan 24, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fingolimod Fingolimod 0.5mg/day tablets taken orally.	Drug: Fingolimod; Fingolimod 0.5 mg tablet; Other Names: FTY720

Outcome Measures

Primary Outcome Measures

1. Participants Who Experienced at Least One Qualifying Cardiovascular Adverse Event [Within 6 months of qualifying event up to 64 months]

   Participants from study CFTY720D2406 who experienced a qualifying cardiovascular adverse event were transferred to this study. Qualifying cardiovascular events included, but were not limited to, sudden unexplained death, cardiovascular death, myocardial infarction (MI), Q-wave MI, stroke (ischemic or hemorrhagic), unstable angina requiring hospitalization, congestive heart failure requiring hospitalization, complete heart block, ventricular fibrillation, torsade de pointes, hypertensive emergency and any other suspected life threatening cardiovascular condition.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients participating in study FTY720D2406 who experienced a serious cardiovascular event during their fingolimod treatment initiation or re-initiation which led to overnight monitoring or met seriousness criteria.

• Patients still on fingolimod after the this first dose serious event

Exclusion Criteria:

-Treatment with any investigational drug unless it is received as part of a Novartis sponsored MS study lasting less than 1 month

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Gent		Belgium	9000
2	Novartis Investigative Site	Hasselt		Belgium	3500
3	Novartis Investigative Site	Ravensburg		Germany	88212
4	Novartis Investigative Site	Napoli		Italy	80131

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Aug 8, 2019
• Statistical Analysis Plan - Aug 21, 2020

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02232061
• Other Study ID Numbers: CFTY720D2409
• First Posted: Sep 4, 2014
• Last Update Posted: Feb 10, 2021
• Last Verified: Jan 1, 2021

• 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: multiple sclerosis, fingolimod, adult, FTY720, inflammatory disease, demyelination, auto-inflammatory disease, relapsing-remitting MS, CFTY720D2406
• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; Fingolimod Hydrochloride

Study Results

Participant Flow

Pre-assignment Detail	Patients enrolled in study CFTY720D2406 who experienced a cardiovascular event within 24-hours of fingolimod treatment initiation/re-initiation which led to overnight monitoring or met serious adverse event criteria, were eligible to participate in this study CFTY720D2409.

Arm/Group Title	Fingolimod
Arm/Group Description	Fingolimod 0.5mg/day tablets taken orally.
Period Title: Overall Study
STARTED	6
COMPLETED	4
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Fingolimod
Arm/Group Description	Fingolimod 0.5mg/day tablets taken orally.
Overall Participants	6
Age, Customized (participants) [Number]
Ages 21 - 47	6 100%
Sex: Female, Male (Count of Participants)
Female	5 83.3%
Male	1 16.7%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	6 100%

Outcome Measures

1. Primary Outcome

Title	Participants Who Experienced at Least One Qualifying Cardiovascular Adverse Event
Description	Participants from study CFTY720D2406 who experienced a qualifying cardiovascular adverse event were transferred to this study. Qualifying cardiovascular events included, but were not limited to, sudden unexplained death, cardiovascular death, myocardial infarction (MI), Q-wave MI, stroke (ischemic or hemorrhagic), unstable angina requiring hospitalization, congestive heart failure requiring hospitalization, complete heart block, ventricular fibrillation, torsade de pointes, hypertensive emergency and any other suspected life threatening cardiovascular condition.
Time Frame	Within 6 months of qualifying event up to 64 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fingolimod
Arm/Group Description	Fingolimod 0.5mg/day tablets taken orally.
Measure Participants	6
Number [participants]	0 0%

Adverse Events

Time Frame	Within 6 months of qualifying event up to approximately 64 months
Arm/Group Title	Fingolimod
Arm/Group Description	Fingolimod 0.5mg/day tablets taken orally
All Cause Mortality
	Fingolimod
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Serious Adverse Events
	Fingolimod
	Affected / at Risk (%)	# Events
Total	2/6 (33.3%)
Blood and lymphatic system disorders
LYMPHOPENIA	1/6 (16.7%)
Infections and infestations
BRONCHITIS VIRAL	1/6 (16.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
ASTHMA	1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	Fingolimod
	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)
Blood and lymphatic system disorders
LYMPHOPENIA	1/6 (16.7%)
Endocrine disorders
HYPOTHYROIDISM	1/6 (16.7%)
Gastrointestinal disorders
HAEMORRHOIDAL HAEMORRHAGE	1/6 (16.7%)
General disorders
PYREXIA	1/6 (16.7%)
Infections and infestations
NASOPHARYNGITIS	1/6 (16.7%)
TRICHOMONIASIS	1/6 (16.7%)
VIRAL PHARYNGITIS	1/6 (16.7%)
Injury, poisoning and procedural complications
INFUSION RELATED REACTION	1/6 (16.7%)
Metabolism and nutrition disorders
FOLATE DEFICIENCY	1/6 (16.7%)
HYPERCHOLESTEROLAEMIA	1/6 (16.7%)
HYPERPHAGIA	1/6 (16.7%)
VITAMIN D DEFICIENCY	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
BURSITIS	1/6 (16.7%)
FACET JOINT SYNDROME	1/6 (16.7%)
MUSCULAR WEAKNESS	1/6 (16.7%)
TENDONITIS	1/6 (16.7%)
Nervous system disorders
HEADACHE	1/6 (16.7%)
MULTIPLE SCLEROSIS RELAPSE	1/6 (16.7%)
SCIATICA	1/6 (16.7%)
Pregnancy, puerperium and perinatal conditions
PREGNANCY	1/6 (16.7%)
Psychiatric disorders
ANXIETY	1/6 (16.7%)
INSOMNIA	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	1/6 (16.7%)
Vascular disorders
HOT FLUSH	1/6 (16.7%)

Limitations/Caveats

This study had no stand-alone secondary objectives. However, data from the CFTY720D2409 and D2406 studies will be pooled to supplement this study and will be appended to this record when available.

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 (i.e., data from all sites) in the clinical trial.