Trial Outcomes & Findings for A Phase IV Study of Rebif ® 44mcg Administered Three Times Per Week by Subcutaneous Injection Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone (NCT NCT01142466)

Last Updated: 2014-02-27

Results Overview

A qualifying relapse was defined as a new or worsening neurological symptom, in the absence of fever, lasting for \>= 48 hours, and accompanied by an objective change in the relevant (i.e. symptomatic) Kurtzke Functional Systems (KFS).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

30 participants

Primary outcome timeframe

Baseline through Week 96

Results posted on

2014-02-27

Participant Flow

Participants were enrolled at multiple centres in Germany.

A total of 36 participants were screened and 30 were randomized to the study treatment. 6 participants were not treated (4 participants were screening failures and 2 participants did not meet the inclusion and exclusion criteria).

Participant milestones

Participant milestones
Measure	Rebif 44 Mcg Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment Participants in this group did not receive any treatment.
Overall Study STARTED	15	15
Overall Study COMPLETED	12	13
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Rebif 44 Mcg Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment Participants in this group did not receive any treatment.
Overall Study Adverse Event	2	1
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

A Phase IV Study of Rebif ® 44mcg Administered Three Times Per Week by Subcutaneous Injection Compared With no Treatment in the Therapy of Relapsing Multiple Sclerosis After Mitoxantrone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rebif 44 Mcg n=14 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 Participants Participants in this group did not receive any treatment.	Total n=29 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 7.0 • n=5 Participants	44.3 years STANDARD_DEVIATION 6.5 • n=7 Participants	44.1 years STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Expanded Disability Status Scale (EDSS)	4.1 Units on Scale STANDARD_DEVIATION 1.4 • n=5 Participants	4.3 Units on Scale STANDARD_DEVIATION 1.0 • n=7 Participants	4.2 Units on Scale STANDARD_DEVIATION 1.2 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline through Week 96

Population: Intent-to-treat (ITT) population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment. Time to relapse was documented for participants who had at least 1 relapse during the study period.

Outcome measures

Outcome measures
Measure	Rebif 44 Mcg n=4 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=8 Participants Participants in this group did not receive any treatment.
Time From Baseline to First Multiple Sclerosis Relapse (in Weeks)	35.5 weeks Standard Deviation 40.8	40.9 weeks Standard Deviation 28.7

SECONDARY outcome

Timeframe: Baseline through Week 96

Population: ITT population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment.

Outcome measures

Outcome measures
Measure	Rebif 44 Mcg n=14 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 Participants Participants in this group did not receive any treatment.
Number of Relapse-free Participants	10 participants	7 participants

SECONDARY outcome

Timeframe: Baseline to Week 24, 48, 72, and 96

Population: ITT population included all participants who received at least 1 treatment dose (only for Rebif group) and had at least 1 post-baseline efficacy endpoint assessment. The 'n' is signifying those participants who received study drug and were evaluated for this measure at the time point for each group respectively.

Analysis of T1 lesions was done using magnetic resonance imaging (MRI) scans.

Outcome measures

Outcome measures
Measure	Rebif 44 Mcg n=14 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 Participants Participants in this group did not receive any treatment.
Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96 Week 24 (n= 13,15)	-0.5 T1 lesions Standard Deviation 4.4	-0.9 T1 lesions Standard Deviation 8.9
Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96 Week 48 (n= 13,13)	-0.8 T1 lesions Standard Deviation 4.3	1.5 T1 lesions Standard Deviation 11.2
Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96 Week 72 (n= 12,12)	-0.8 T1 lesions Standard Deviation 9.2	-3.6 T1 lesions Standard Deviation 12.0
Absolute Changes in the Number of T1 Lesions From Baseline to Week 24, 48, 72 and 96 Week 96 (n= 12,12)	-1.8 T1 lesions Standard Deviation 5.5	-2.3 T1 lesions Standard Deviation 11.6

SECONDARY outcome

Timeframe: Baseline to Week 24, 48, 72, and 96

Population: The data was not evaluated due to the small sample size available for this parameter.

Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Week 24, 48, 72, and 96

Analysis of T2 lesions was done using magnetic resonance imaging (MRI) scans.

Outcome measures

Outcome measures
Measure	Rebif 44 Mcg n=14 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 Participants Participants in this group did not receive any treatment.
Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96 Week 24 (n= 13,15)	-1.2 T2 lesions Standard Deviation 4.0	1.0 T2 lesions Standard Deviation 6.0
Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96 Week 48 (n= 13,13)	0.2 T2 lesions Standard Deviation 8.5	3.2 T2 lesions Standard Deviation 10.1
Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96 Week 72 (n= 12,13)	-1.8 T2 lesions Standard Deviation 3.3	3.1 T2 lesions Standard Deviation 14.1
Absolute Changes in the Number of T2 Lesions From Baseline to Week 24, 48, 72 and 96 Week 96 (n= 12,12)	-3.1 T2 lesions Standard Deviation 7.6	2.1 T2 lesions Standard Deviation 15.4

SECONDARY outcome

Timeframe: Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96

EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. EDSS progression was defined as increase by at least 1 point if last value of EDSS was equal to 5.5, and by at least 0.5 points if last EDSS was more than 5.5.

Outcome measures

Outcome measures
Measure	Rebif 44 Mcg n=14 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 Participants Participants in this group did not receive any treatment.
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 12 (n= 14, 15)	-0.1 Units on a Scale Standard Deviation 0.5	-0.1 Units on a Scale Standard Deviation 0.4
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 24 (n= 14, 15)	0.3 Units on a Scale Standard Deviation 0.6	0.1 Units on a Scale Standard Deviation 0.4
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 36 (n= 13, 14)	0.5 Units on a Scale Standard Deviation 0.8	-0.2 Units on a Scale Standard Deviation 0.4
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 48 (n= 14, 14)	0.5 Units on a Scale Standard Deviation 0.8	0.2 Units on a Scale Standard Deviation 0.7
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 60 (n= 10, 11)	0.4 Units on a Scale Standard Deviation 0.8	0.0 Units on a Scale Standard Deviation 1.0
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 72 (n= 12, 13)	0.3 Units on a Scale Standard Deviation 0.6	0.2 Units on a Scale Standard Deviation 0.9
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 84 (n= 12, 13)	0.5 Units on a Scale Standard Deviation 0.9	0.2 Units on a Scale Standard Deviation 0.9
Mean Changes in Expanded Disability Status Scale (EDSS) Score From Baseline to Week 12, 24, 36, 48, 60, 72, 84, and 96 Week 96 (n= 12, 13)	0.1 Units on a Scale Standard Deviation 0.8	0.3 Units on a Scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline to Week 96

Population: Safety population included all participants all randomized participants of the active treatment group who received at least 1 injection and all randomized participants of the 'No Treatment' group, provided that any post-baseline data was available.

AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.

Outcome measures

Outcome measures
Measure	Rebif 44 Mcg n=15 Participants Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 Participants Participants in this group did not receive any treatment.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Adverse Events	15 participants	14 participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Serious Adverse Events	5 participants	1 participants

Adverse Events

Rebif 44 Mcg

Serious events: 5 serious events

Other events: 15 other events

Deaths: 0 deaths

No Treatment

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rebif 44 Mcg n=15 participants at risk Rebif was administered subcutaneously (s.c.) at a dose of 44 microgram (mcg), three times a week.	No Treatment n=15 participants at risk Participants in this group did not receive any treatment.
Nervous system disorders Convulsion	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Status Epilepticus	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Eye disorders Angle Closure Glaucoma	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Hepatobiliary disorders Cholecystitis chronic	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Hepatobiliary disorders Cholelithiasis	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Haemorrhoid Operation	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Gastrointestinal disorders Gastroenteritis salmonella	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.
Nervous system disorders Depression	0.00% 0/15 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.	6.7% 1/15 • Number of events 1 • Baseline to Week 96 or premature termination or unscheduled visit. An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

Other adverse events

Additional Information

Medical Responsible

Merck Serono GmbH, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49 6151 72 5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER