Trial Outcomes & Findings for Assessment of Tecfidera® in Radiologically Isolated Syndrome (RIS) (NCT NCT02739542)

Last Updated: 2022-05-11

Results Overview

The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination from randomization into the trial.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

87 participants

Primary outcome timeframe

96 weeks

Results posted on

2022-05-11

Participant Flow

Participant milestones

Participant milestones
Measure	Tecfidera Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Overall Study STARTED	44	43
Overall Study COMPLETED	30	29
Overall Study NOT COMPLETED	14	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

11 missing data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tecfidera n=44 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=43 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Total n=87 Participants Total of all reporting groups
Age, Continuous	43.57 years STANDARD_DEVIATION 12.87 • n=44 Participants	44.81 years STANDARD_DEVIATION 13.88 • n=43 Participants	44.18 years STANDARD_DEVIATION 13.32 • n=87 Participants
Sex: Female, Male Female	31 Participants n=44 Participants	30 Participants n=43 Participants	61 Participants n=87 Participants
Sex: Female, Male Male	13 Participants n=44 Participants	13 Participants n=43 Participants	26 Participants n=87 Participants
Race/Ethnicity, Customized White	40 Participants n=44 Participants	38 Participants n=43 Participants	78 Participants n=87 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=44 Participants	3 Participants n=43 Participants	5 Participants n=87 Participants
Race/Ethnicity, Customized Other	2 Participants n=44 Participants	2 Participants n=43 Participants	4 Participants n=87 Participants
Expanded Disability Status Scale (EDSS)	1 units on a scale n=44 Participants	1 units on a scale n=43 Participants	1 units on a scale n=87 Participants
Multiple Sclerosis (MS) family history	3 Participants n=44 Participants	6 Participants n=43 Participants	9 Participants n=87 Participants
Presence of gadolinium enhancing lesions	6 Participants n=38 Participants • 11 missing data	2 Participants n=38 Participants • 11 missing data	8 Participants n=76 Participants • 11 missing data
T2-weighted hyperintense lesion volume	7.30 mm^3 STANDARD_DEVIATION 1.07 • n=40 Participants • 4 missing data	7.32 mm^3 STANDARD_DEVIATION 0.89 • n=43 Participants • 4 missing data	7.31 mm^3 STANDARD_DEVIATION 0.97 • n=83 Participants • 4 missing data

PRIMARY outcome

Timeframe: 96 weeks

The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination from randomization into the trial.

Outcome measures

Outcome measures
Measure	Tecfidera n=44 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=43 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
The Time From Randomization to the First Demyelinating Event (Acute or Development of an Initial Symptom Resulting in a Progressive Clinical Course)	89.69 weeks Standard Deviation 23.99	77.81 weeks Standard Deviation 32.19

SECONDARY outcome

Timeframe: Baseline, 96 weeks

Population: 3 participants out of 30 who completed the assigned treatment, their baseline MRI data was missing and hence were not analyzed. 3 participants out of 29 who completed the assigned placebo arm, their MRI data was not collected due to technical issues and hence were not analyzed.

Change in lesion volume on T2-weighted MRI is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.

Outcome measures

Outcome measures
Measure	Tecfidera n=27 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=26 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Change in Lesion Volume on T2-weighted MRI	0.005 mm³ Standard Deviation 0.03	0.04 mm³ Standard Deviation 0.03

SECONDARY outcome

Timeframe: 96 weeks

Number of newly enlarging T2 lesions is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.

Outcome measures

Outcome measures
Measure	Tecfidera n=27 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=26 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Number of Newly Enlarging T2 Lesions	0.03 T2 lesions Standard Deviation 0.003	0.10 T2 lesions Standard Deviation 0.07

SECONDARY outcome

Timeframe: 96 weeks

Number of new T2 lesions as measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.

Outcome measures

Outcome measures
Measure	Tecfidera n=27 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=26 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Number of New T2 Lesions	0.09 T2 lesions Standard Deviation 0.06	0.54 T2 lesions Standard Deviation 0.28

SECONDARY outcome

Timeframe: 96 weeks

Newly enlarging T2 lesions and new T2 lesions combined is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.

Outcome measures

Outcome measures
Measure	Tecfidera n=27 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=26 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Newly Enlarging T2 Lesions and New T2 Lesions Combined	0.12 T2 lesions Standard Deviation 0.07	0.62 T2 lesions Standard Deviation 0.30

SECONDARY outcome

Timeframe: 96 weeks

Number of contrast enhancing lesions is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.

Outcome measures

Outcome measures
Measure	Tecfidera n=27 Participants Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=26 Participants Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Number of Contrast Enhancing Lesions	0.07 contrast enhancing lesions Standard Deviation 0.38	0 contrast enhancing lesions Standard Deviation 0

SECONDARY outcome

Timeframe: Baseline, 96 weeks

Population: Data were not collected.

Change in the number of participants with brain atrophy is measured by follow-up MRI at 96 weeks in the placebo group and in the Tecfidera group.

Outcome measures

Outcome data not reported

Adverse Events

Tecfidera

Serious events: 4 serious events

Other events: 44 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Tecfidera n=44 participants at risk Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=43 participants at risk Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Injury, poisoning and procedural complications Procedural headache	0.00% 0/44 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	2.3% 1/43 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Musculoskeletal and connective tissue disorders Spondylolysis	0.00% 0/44 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	2.3% 1/43 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.00% 0/44 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	2.3% 1/43 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Nervous system disorders Migraine	0.00% 0/44 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	2.3% 1/43 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Nervous system disorders Spontaneous cerebrospinal fluid leak syndrome	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.

Other adverse events

Additional Information

Darin T. Okuda, M.D.

UT Southwestern Medical Center

Phone: 214-645-8800

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Tecfidera n=44 participants at risk Tecfidera (120mg by mouth twice daily for 7 days with dose escalation to 240mg by mouth twice daily) Tecfidera: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.	Placebo n=43 participants at risk Placebo by mouth twice daily. Placebo: Blinded drug wallets will be dispensed during routine study appointments in 3 month supply, so that compliance can be reconciled at follow up visits and telephone consultations, and recorded in accountability logs.
Eye disorders Vision blurred	0.00% 0/44 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	7.0% 3/43 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Gastrointestinal disorders Constipation	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	9.3% 4/43 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Gastrointestinal disorders Diarrhoea	6.8% 3/44 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	2.3% 1/43 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
General disorders Chest discomfort	6.8% 3/44 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
General disorders Fatigue	9.1% 4/44 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	9.3% 4/43 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Infections and infestations Nasopharyngitis	9.1% 4/44 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	4.7% 2/43 • Number of events 2 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Infections and infestations Sinusitis	11.4% 5/44 • Number of events 6 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	7.0% 3/43 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Injury, poisoning and procedural complications Fall	6.8% 3/44 • Number of events 7 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	2.3% 1/43 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Investigations Blood glucose increased	6.8% 3/44 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/44 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	11.6% 5/43 • Number of events 5 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	7.0% 3/43 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Musculoskeletal and connective tissue disorders Muscular weakness	2.3% 1/44 • Number of events 1 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	7.0% 3/43 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Nervous system disorders Dizziness	4.5% 2/44 • Number of events 2 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	7.0% 3/43 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Nervous system disorders Headache	15.9% 7/44 • Number of events 8 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	14.0% 6/43 • Number of events 6 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Nervous system disorders Hypoaesthesia	13.6% 6/44 • Number of events 6 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	11.6% 5/43 • Number of events 6 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Nervous system disorders Paraesthesia	13.6% 6/44 • Number of events 6 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	11.6% 5/43 • Number of events 6 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Skin and subcutaneous tissue disorders Urticaria	9.1% 4/44 • Number of events 4 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	0.00% 0/43 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.
Vascular disorders Flushing	50.0% 22/44 • Number of events 24 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.	7.0% 3/43 • Number of events 3 • 2 years Adverse Events (AE) occurred during 2 years of follow up. AEs were routinely determined through regular investigator assessment.