Trial Outcomes & Findings for A Study to Evaluate Rebif® New Formulation (Interferon-beta-1a) in Relapsing Remitting Multiple Sclerosis (NCT NCT00441103)
NCT ID: NCT00441103
Last Updated: 2014-07-09
Results Overview
CU active lesions were defined as a unique newly active or persistently active lesion on the protocol density/time constant 2 (PD/T2) scan or the gadolinium (Gd-) enhanced time constant 1 (T1) scan (with a method to avoid double counting).
COMPLETED
PHASE3
180 participants
16 Weeks
2014-07-09
Participant Flow
Date of first participant first visit: 15 Dec 2006. Date of last participant last visit: 28 Nov 2008. Twenty five trial centers enrolled participants in the following countries: Bulgaria (7), Canada(2), Estonia (2), Germany (1), Italy(2), Lithuania (1), Romania (1), Russian Federation (4), Serbia (2), and Spain (3).
Participants meeting the eligibility criteria during screening period of up to 14 days were randomly assigned in a 2:1 ratio to receive either Rebif® New Formulation or matching placebo for 16 weeks. There were 33 screening failures: participants who did not meet all eligibility criteria (n=29), withdrawal of consent (n=3), and lost of view (n=1).
Participant milestones
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
RNF 44 microgram (mcg) administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
120
|
60
|
|
Overall Study
COMPLETED
|
109
|
56
|
|
Overall Study
NOT COMPLETED
|
11
|
4
|
Reasons for withdrawal
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
RNF 44 microgram (mcg) administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Disease Progression
|
2
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Participant unable to use Rebiject II
|
1
|
0
|
|
Overall Study
Participant refused MRI
|
1
|
0
|
|
Overall Study
Inclusion criteria absent
|
1
|
0
|
|
Overall Study
Non-compliant
|
0
|
1
|
|
Overall Study
Participant decided to withdraw
|
1
|
0
|
|
Overall Study
Participant's reason
|
0
|
1
|
|
Overall Study
Participant decided to stop
|
0
|
1
|
Baseline Characteristics
A Study to Evaluate Rebif® New Formulation (Interferon-beta-1a) in Relapsing Remitting Multiple Sclerosis
Baseline characteristics by cohort
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=120 Participants
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
n=60 Participants
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
Total
n=180 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Region of Enrollment
Romania
|
11 participants
n=5 Participants
|
8 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Region of Enrollment
Russian Federation
|
20 participants
n=5 Participants
|
12 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Serbia
|
20 participants
n=5 Participants
|
9 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
120 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
180 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
34.0 years
STANDARD_DEVIATION 7.8 • n=5 Participants
|
35.2 years
STANDARD_DEVIATION 10.5 • n=7 Participants
|
34.4 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
88 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
40 participants
n=5 Participants
|
12 participants
n=7 Participants
|
52 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Estonia
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
7 participants
n=5 Participants
|
4 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Lithuania
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
8 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 16 WeeksPopulation: ITT population included all randomized participants who received at least one dose of study drug.
CU active lesions were defined as a unique newly active or persistently active lesion on the protocol density/time constant 2 (PD/T2) scan or the gadolinium (Gd-) enhanced time constant 1 (T1) scan (with a method to avoid double counting).
Outcome measures
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=120 Participants
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
n=60 Participants
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Number of Combined Unique (CU) Active Magnetic Resonance Imaging (MRI) Lesions at Week 16
|
0.9 lesions
Standard Deviation 1.4
|
3.0 lesions
Standard Deviation 4.1
|
PRIMARY outcome
Timeframe: Baseline up to Week 40Population: Safety population included all randomized participants who received at least one dose of study drug. Here, 'n' signifies those participants who were evaluable for the specified category.
An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. AEs were categorized based upon the treatment period during which they occurred, that is, double-blind period (up to Week 16) and rater-blind period (Week 17 up to Week 40).
Outcome measures
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=120 Participants
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
n=60 Participants
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs during double-blind period (n = 120, 60)
|
100 participants
|
39 participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs during rater-blind period (n = 112, 57)
|
72 participants
|
43 participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs during overall period (n = 120, 60)
|
4 participants
|
3 participants
|
SECONDARY outcome
Timeframe: Day 1 up to Week 16 and Week 17 up to Week 40Population: ITT population included all randomized participants who received at least one dose of study drug. Here, "N" (number of participants analyzed) signifies those participants who were evaluable for this measure.
CU active lesions were defined as a unique newly active or persistently active lesion on the PD/T2 scan or the gadolinium enhanced T1 scan (with a method to avoid double counting). Only "Placebo Followed by RNF" arm was evaluable for this outcome measure.
Outcome measures
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=57 Participants
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Mean Number of CU Lesions Per Scan Between the Initial 16 Weeks of Placebo Treatment and 24 Weeks of RNF Treatment in the Same Participants, Originally Randomized to Placebo.
Week 17 up to Week 40
|
0.65 lesions
Standard Deviation 0.95
|
—
|
|
Mean Number of CU Lesions Per Scan Between the Initial 16 Weeks of Placebo Treatment and 24 Weeks of RNF Treatment in the Same Participants, Originally Randomized to Placebo.
Day 1 up to Week 16
|
2.31 lesions
Standard Deviation 2.63
|
—
|
SECONDARY outcome
Timeframe: Up to Week 40Population: ITT population included all randomized participants who received at least one dose of study drug.
CU active lesions were defined as a unique newly active or persistently active lesion on the PD/T2 scan or the gadolinium enhanced T1 scan (with a method to avoid double counting).
Outcome measures
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=120 Participants
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
n=60 Participants
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Number of CU Active MRI Lesions
|
0.62 lesions
Standard Deviation 1.29
|
1.27 lesions
Standard Deviation 1.33
|
Adverse Events
Rebif® New Formulation (IFN-beta-1a, RNF)
Placebo/RNF
Serious adverse events
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=120 participants at risk
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
n=60 participants at risk
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
Infections and infestations
Tonsillitis
|
0.83%
1/120 • Number of events 1 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.00%
0/120 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 1 • Baseline up to Week 40
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.83%
1/120 • Number of events 1 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Infections and infestations
Pyelonephritis acute
|
0.83%
1/120 • Number of events 1 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.83%
1/120 • Number of events 1 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/120 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 1 • Baseline up to Week 40
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.00%
0/120 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 1 • Baseline up to Week 40
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/120 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 1 • Baseline up to Week 40
|
Other adverse events
| Measure |
Rebif® New Formulation (IFN-beta-1a, RNF)
n=120 participants at risk
RNF 44 mcg administered subcutaneously three times a week for 40 weeks.
|
Placebo/RNF
n=60 participants at risk
Matching placebo administered subcutaneously three times a week for 16 weeks, followed by RNF 44 mcg administered subcutaneously three times a week for subsequent 24 weeks.
|
|---|---|---|
|
General disorders
Influenza like illness
|
50.0%
60/120 • Number of events 110 • Baseline up to Week 40
|
16.7%
10/60 • Number of events 10 • Baseline up to Week 40
|
|
General disorders
Injection site erythema
|
32.5%
39/120 • Number of events 60 • Baseline up to Week 40
|
6.7%
4/60 • Number of events 6 • Baseline up to Week 40
|
|
General disorders
Injection site pain
|
10.0%
12/120 • Number of events 13 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 1 • Baseline up to Week 40
|
|
General disorders
Pyrexia
|
7.5%
9/120 • Number of events 14 • Baseline up to Week 40
|
5.0%
3/60 • Number of events 5 • Baseline up to Week 40
|
|
General disorders
Asthenia
|
6.7%
8/120 • Number of events 11 • Baseline up to Week 40
|
5.0%
3/60 • Number of events 8 • Baseline up to Week 40
|
|
General disorders
Chills
|
6.7%
8/120 • Number of events 11 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 3 • Baseline up to Week 40
|
|
General disorders
Fatigue
|
5.8%
7/120 • Number of events 8 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Nervous system disorders
Headache
|
30.8%
37/120 • Number of events 66 • Baseline up to Week 40
|
16.7%
10/60 • Number of events 17 • Baseline up to Week 40
|
|
Nervous system disorders
Dizziness
|
2.5%
3/120 • Number of events 3 • Baseline up to Week 40
|
6.7%
4/60 • Number of events 4 • Baseline up to Week 40
|
|
Infections and infestations
Nasopharyngitis
|
5.8%
7/120 • Number of events 7 • Baseline up to Week 40
|
3.3%
2/60 • Number of events 3 • Baseline up to Week 40
|
|
Infections and infestations
Upper respiratory tract infection
|
3.3%
4/120 • Number of events 5 • Baseline up to Week 40
|
6.7%
4/60 • Number of events 4 • Baseline up to Week 40
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
6/120 • Number of events 7 • Baseline up to Week 40
|
3.3%
2/60 • Number of events 2 • Baseline up to Week 40
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.0%
6/120 • Number of events 7 • Baseline up to Week 40
|
1.7%
1/60 • Number of events 1 • Baseline up to Week 40
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.0%
6/120 • Number of events 7 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Investigations
Alanine aminotransferase increased
|
5.8%
7/120 • Number of events 7 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
6/120 • Number of events 6 • Baseline up to Week 40
|
0.00%
0/60 • Baseline up to Week 40
|
|
Psychiatric disorders
Anxiety
|
1.7%
2/120 • Number of events 2 • Baseline up to Week 40
|
5.0%
3/60 • Number of events 4 • Baseline up to Week 40
|
|
Ear and labyrinth disorders
Vertigo
|
0.83%
1/120 • Number of events 1 • Baseline up to Week 40
|
5.0%
3/60 • Number of events 4 • Baseline up to Week 40
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER