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Trial record 1 of 2 for:    NCT00404352
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REbif FLEXible Dosing in Early Multiple Sclerosis (MS) (REFLEX)

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ClinicalTrials.gov Identifier: NCT00404352
Recruitment Status : Completed
First Posted : November 28, 2006
Results First Posted : September 24, 2012
Last Update Posted : January 24, 2014
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Multiple Sclerosis
Interventions Drug: RNF
Drug: Placebo
Enrollment 517
Recruitment Details The participants were recruited in 78 centers across 28 countries for REFLEX study. REFLEX 12 months open label extension (OLE) was conducted at 11 active centers in 9 countries.
Pre-assignment Details  
Arm/Group Title RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population) RNF 44 Mcg Three Times Weekly/OL RNF 44 Mcg Three Times Weekly RNF 44 Mcg Once Weekly/OL RNF 44 Mcg Three Times Weekly Placebo/OL RNF 44 Mcg Three Times Weekly RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description Single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF) injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. Single dose of matching placebo administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension. Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension. Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Period Title: Double Blind (up to 24 Month)
Started 171 175 171 0 0 0 0 0 0
Treated 171 173 171 0 0 0 0 0 0
Completed 119 128 92 0 0 0 0 0 0
Not Completed 52 47 79 0 0 0 0 0 0
Reason Not Completed
Adverse Event             5             4             6             0             0             0             0             0             0
Pregnancy             0             0             2             0             0             0             0             0             0
Death             0             0             1             0             0             0             0             0             0
Lost to Follow-up             1             2             1             0             0             0             0             0             0
Withdrawal by Subject             11             8             7             0             0             0             0             0             0
Disease progression             3             0             2             0             0             0             0             0             0
Poor compliance             1             0             0             0             0             0             0             0             0
Switched to open label phase             31             30             59             0             0             0             0             0             0
Randomized but not treated             0             2             0             0             0             0             0             0             0
Physician Decision             0             0             1             0             0             0             0             0             0
Other             0             1             0             0             0             0             0             0             0
Period Title: Open Label (up to 24 Month)
Started 0 0 0 31 [1] 30 [2] 59 [3] 0 0 0
Completed 0 0 0 28 28 52 0 0 0
Not Completed 0 0 0 3 2 7 0 0 0
Reason Not Completed
Adverse Event             0             0             0             2             1             1             0             0             0
Pregnancy             0             0             0             0             0             1             0             0             0
Lost to Follow-up             0             0             0             0             1             0             0             0             0
Withdrawal by Subject             0             0             0             0             0             5             0             0             0
Disease progression             0             0             0             1             0             0             0             0             0
[1]
From DB period, 31 participants converted to CDMS and switched to OL period in this study
[2]
From DB period, 30 participants converted to CDMS and switched to OL period in this study
[3]
From DB period, 59 participants converted to CDMS and switched to OL period in this study
Period Title: Open Label Extension (up to 36 Months)
Started 0 0 0 0 0 0 4 [1] 5 [2] 11 [3]
Completed 0 0 0 0 0 0 3 4 9
Not Completed 0 0 0 0 0 0 1 1 2
Reason Not Completed
Adverse Event             0             0             0             0             0             0             1             1             0
Other             0             0             0             0             0             0             0             0             2
[1]
4 participants who did not convert to CDMS in 24 months and gave consent to enroll in OLE period
[2]
5 participants who did not convert to CDMS in 24 months and gave consent to enroll in OLE period
[3]
11 participants who did not convert to CDMS in 24 months and gave consent to enroll in OLE period
Arm/Group Title RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population) Total
Hide Arm/Group Description Single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF) injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. Single dose of matching placebo administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. Total of all reporting groups
Overall Number of Baseline Participants 171 175 171 517
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 171 participants 175 participants 171 participants 517 participants
30.6  (8.5) 30.7  (8.1) 30.9  (7.9) 30.7  (8.2)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 171 participants 175 participants 171 participants 517 participants
Less than 30 years 86 86 87 259
Greater than or equal to 30 years 85 89 84 258
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 171 participants 175 participants 171 participants 517 participants
Female
114
  66.7%
106
  60.6%
112
  65.5%
332
  64.2%
Male
57
  33.3%
69
  39.4%
59
  34.5%
185
  35.8%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 171 participants 175 participants 171 participants 517 participants
Asian 0 0 0 0
Black 0 1 0 1
White 171 174 171 516
Other 0 0 0 0
1.Primary Outcome
Title Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
Hide Description The McDonald criteria use dissemination in time and space established by magnetic resonance image (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium-enhancing (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions.
Time Frame Various time points from randomization up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all participants who were randomized to the assigned study treatment.
Arm/Group Title RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population)
Hide Arm/Group Description:
Single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF) injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first.
Single dose of matching placebo administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first.
Overall Number of Participants Analyzed 171 175 171
Median (95% Confidence Interval)
Unit of Measure: days
310
(183 to 488)
182
(107 to 270)
97
(93 to 101)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population), Placebo (DB Population)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments Log-rank test was stratified for controlling randomization stratification factors.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RNF 44 Mcg Once Weekly (DB Population), Placebo (DB Population)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Log Rank
Comments Log-rank test was stratified for controlling randomization stratification factors.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population), RNF 44 Mcg Once Weekly (DB Population)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Log Rank
Comments Log-rank test was stratified for controlling randomization stratification factors.
2.Primary Outcome
Title Time to Conversion to Multiple Sclerosis (MS) According to the McDonald Criteria (2005)
Hide Description The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a T2 or Gd+ lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions.
Time Frame Various time points from randomization up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
Open label (OL) ITT population included all participants who were randomized at baseline in core REFLEX trial and entered the 12 months OLE period.
Arm/Group Title RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description:
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Overall Number of Participants Analyzed 4 5 11
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Data could not be analyzed as none of the participants converted to MS according to the McDonald Criteria in the 12 month OLE period.
3.Secondary Outcome
Title Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score
Hide Description CDMS was defined by the occurrence of a second exacerbation or relapse over 24 months in participants who presented with first clinical demyelinating event (FCDE) accompanied by an abnormal MRI scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Time Frame Various time points from randomization up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all participants who were randomized to the assigned study treatment.
Arm/Group Title RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population)
Hide Arm/Group Description:
Single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF) injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first.
Single dose of matching placebo administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first.
Overall Number of Participants Analyzed 171 175 171
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Non-estimable: Insufficient participants reached the median percentile to calculate the upper and lower limits of confidence interval.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population), Placebo (DB Population)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Log Rank
Comments Log-rank test was stratified for controlling randomization stratification factors.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection RNF 44 Mcg Once Weekly (DB Population), Placebo (DB Population)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Log Rank
Comments Log-rank test was stratified for controlling randomization stratification factors.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population), RNF 44 Mcg Once Weekly (DB Population)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.774
Comments [Not Specified]
Method Log Rank
Comments Log-rank test was stratified for controlling randomization stratification factors.
4.Secondary Outcome
Title Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a 3-Month Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score
Hide Description CDMS was defined by the occurrence of a second exacerbation or relapse over 36 months in participants who presented with FCDE accompanied by an abnormal MRI scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Time Frame Various time points from randomization up to 36 months
Hide Outcome Measure Data
Hide Analysis Population Description
OL ITT population included all participants who were randomized at baseline in core REFLEX trial and entered the 12 months OLE period.
Arm/Group Title RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description:
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Overall Number of Participants Analyzed 4 5 11
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Insufficient participants reached the median percentile to calculate the upper and lower limits of confidence interval.
5.Secondary Outcome
Title Mean Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Hypointense Lesions Per Participant Per Scan
Hide Description Number of CUA lesions, new T2 lesions, Gd+ lesions and new T1 hypointense lesions were measured by using MRI scans.
Time Frame Month 24 up to Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
OL ITT population included all participants who were randomized at baseline in core REFLEX trial and entered the 12 months OLE period. "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Arm/Group Title RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description:
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Overall Number of Participants Analyzed 4 5 11
Mean (Standard Deviation)
Unit of Measure: lesions
CUA lesions (n=3,5,9) 0.33  (0.58) 0.00  (0.00) 1.56  (2.93)
New T2 lesions (n=3,5,9) 0.17  (0.29) 0.00  (0.00) 0.94  (1.61)
New Gd+ lesions (n=3,5,9) 0.17  (0.29) 0.00  (0.00) 0.56  (1.21)
New T1 Hypointense lesions (n=3,5,9) 0.17  (0.29) 0.00  (0.00) 0.56  (0.88)
6.Secondary Outcome
Title Change From Baseline in Time Constant 2 (T2) Lesion Volume , Time Constant 1 (T1) Hypointense Lesion Volume and Gadolinium Enhanced (Gd+) Lesion Volume at Month 36
Hide Description Change from baseline in lesion volume was measured by using MRI scans for T2 lesions, T1 hypointense lesions and (Gd+) lesions.
Time Frame Baseline, Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
OL ITT population included all participants who were randomized at baseline in core REFLEX trial and entered the 12 months OLE period. "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Arm/Group Title RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description:
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Overall Number of Participants Analyzed 4 5 11
Mean (Standard Deviation)
Unit of Measure: cubic millimeter (mm^3)
T2 lesion volume at Baseline (n=4,5,11) 675.20  (940.87) 1703.48  (1324.41) 3533.37  (3914.98)
T2 lesion volume change at Month 36 (n=2,4,8) 180.25  (198.34) -22.63  (382.14) -1155.63  (3348.36)
T1 lesion volume at Baseline (n=4,5,11) 30.05  (60.10) 302.70  (358.58) 488.72  (589.06)
T1 lesion volume change at Month 36 (n=2,4,8) 55.75  (78.84) 216.68  (310.06) 138.89  (339.99)
Gd+ lesion volume at Baseline (n=4,5,11) 103.70  (151.17) 0.00  (0.00) 287.15  (649.68)
Gd+ lesion volume change at Month 36 (n=2,4,8) -47.20  (66.75) 0.00  (0.00) -246.08  (848.99)
7.Secondary Outcome
Title Change From Baseline in Expanded Disability Status Score (EDSS) Score at Month 36
Hide Description EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS at Month 36 was calculated as EDSS at Month 36 minus EDSS at baseline.
Time Frame Baseline, Month 36
Hide Outcome Measure Data
Hide Analysis Population Description
OL ITT population included all participants who were randomized at baseline in core REFLEX trial and entered the 12 months OLE period. "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Arm/Group Title RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description:
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
Overall Number of Participants Analyzed 4 5 11
Mean (Standard Deviation)
Unit of Measure: unit on a scale
Baseline (n=4,5,11) 1.88  (0.85) 1.60  (0.96) 1.64  (0.67)
Change at Month 36 (n=2,4,8) -0.25  (1.06) -0.63  (0.48) -0.50  (0.65)
Time Frame [Not Specified]
Adverse Event Reporting Description 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.
 
Arm/Group Title RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population) RNF 44 Mcg Three Times Weekly/OL RNF 44 Mcg Three Times Weekly RNF 44 Mcg Once Weekly/OL RNF 44 Mcg Three Times Weekly Placebo/OL RNF 44 Mcg Three Times Weekly RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Hide Arm/Group Description Single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF) injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. Single dose of matching placebo administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 24 months. Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year open label extension (OLE). Participants who had received RNF three times a week in the core REFLEX trial, were re-titrated with a single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension. Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received RNF once weekly in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension. Participants who were not converted to CDMS and completed 24 month core REFLEX trial were enrolled in a 1 year OLE. Participants who had received placebo in the core REFLEX trial were re-titrated with a single dose of RNF injection subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months in this 12 months open label extension.
All-Cause Mortality
RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population) RNF 44 Mcg Three Times Weekly/OL RNF 44 Mcg Three Times Weekly RNF 44 Mcg Once Weekly/OL RNF 44 Mcg Three Times Weekly Placebo/OL RNF 44 Mcg Three Times Weekly RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population) RNF 44 Mcg Three Times Weekly/OL RNF 44 Mcg Three Times Weekly RNF 44 Mcg Once Weekly/OL RNF 44 Mcg Three Times Weekly Placebo/OL RNF 44 Mcg Three Times Weekly RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/171 (3.51%)      8/173 (4.62%)      12/171 (7.02%)      1/31 (3.23%)      0/30 (0.00%)      1/59 (1.69%)      0/4 (0.00%)      0/5 (0.00%)      0/11 (0.00%)    
Blood and lymphatic system disorders                   
Iron deficiency anemia † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Cardiac disorders                   
Acute myocardial infarction † 1  1/171 (0.58%)  1 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Angina unstable † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Congenital, familial and genetic disorders                   
Deafness congenital † 1  1/171 (0.58%)  1 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Dermoid cyst † 1  1/171 (0.58%)  1 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Ear and labyrinth disorders                   
Hypoacusis † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Gastrointestinal disorders                   
Gastrointestinal motility disorder † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Inguinal hernia † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Pancreatic necrosis † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Hepatobiliary disorders                   
Cholelithiasis † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 1/31 (3.23%)  1 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Infections and infestations                   
Appendicitis † 1  3/171 (1.75%)  3 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Tonsillitis † 1  1/171 (0.58%)  1 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Varicella † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Injury, poisoning and procedural complications                   
Muscle rupture † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Post procedural hematoma † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Tibia fracture † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Breast cancer stage III † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Ovarian germ cell teratoma benign † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Testis cancer † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Nervous system disorders                   
Ischemic stroke † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Pregnancy, puerperium and perinatal conditions                   
Abortion spontaneous † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 1/171 (0.58%)  1 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Psychiatric disorders                   
Psychotic disorder † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 1/59 (1.69%)  1 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Reproductive system and breast disorders                   
Ovarian cyst † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 2/171 (1.17%)  2 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Cervical polyp † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Nasal septum deviation † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Tonsillar disorder † 1  0/171 (0.00%)  0 1/173 (0.58%)  1 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
RNF 44 Mcg Three Times Weekly (Double Blind [DB] Population) RNF 44 Mcg Once Weekly (DB Population) Placebo (DB Population) RNF 44 Mcg Three Times Weekly/OL RNF 44 Mcg Three Times Weekly RNF 44 Mcg Once Weekly/OL RNF 44 Mcg Three Times Weekly Placebo/OL RNF 44 Mcg Three Times Weekly RNF 44Mcg Three Times Weekly/RNF 44Mcg Three Times Weekly(OLE) RNF 44 Mcg Once Weekly/RNF 44 Mcg Three Times Weekly (OLE) Placebo/RNF 44 Mcg Three Times Weekly (OLE)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   149/171 (87.13%)      156/173 (90.17%)      133/171 (77.78%)      20/31 (64.52%)      20/30 (66.67%)      47/59 (79.66%)      3/4 (75.00%)      2/5 (40.00%)      5/11 (45.45%)    
Blood and lymphatic system disorders                   
Neutropenia † 1  13/171 (7.60%)  15 6/173 (3.47%)  7 1/171 (0.58%)  1 0/31 (0.00%)  0 2/30 (6.67%)  2 3/59 (5.08%)  5 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Leukopenia † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 3/31 (9.68%)  3 3/30 (10.00%)  3 2/59 (3.39%)  4 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Thrombocytopenia † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 1/31 (3.23%)  1 3/30 (10.00%)  3 1/59 (1.69%)  1 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Lymphopenia † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  1/11 (9.09%) 
Iron deficiency anaemia † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Endocrine disorders                   
Hyperthyroidism † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  1/11 (9.09%) 
Gastrointestinal disorders                   
Toothache † 1  6/171 (3.51%)  7 10/173 (5.78%)  12 6/171 (3.51%)  9 2/31 (6.45%)  2 1/30 (3.33%)  1 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Diarrhea † 1  4/171 (2.34%)  5 4/173 (2.31%)  5 9/171 (5.26%)  9 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Nausea † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 2/30 (6.67%)  4 1/59 (1.69%)  1 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Aphthous stomatitis † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/11 (0.00%) 
Constipation † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
General disorders                   
Influenza like illness † 1  93/171 (54.39%)  218 122/173 (70.52%)  374 34/171 (19.88%)  50 8/31 (25.81%)  9 3/30 (10.00%)  6 24/59 (40.68%)  31 1/4 (25.00%)  1/5 (20.00%)  1/11 (9.09%) 
Injection site erythema † 1  50/171 (29.24%)  76 34/173 (19.65%)  49 3/171 (1.75%)  3 4/31 (12.90%)  5 3/30 (10.00%)  5 13/59 (22.03%)  13 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Pyrexia † 1  6/171 (3.51%)  13 22/173 (12.72%)  29 9/171 (5.26%)  12 0/31 (0.00%)  0 2/30 (6.67%)  2 2/59 (3.39%)  4 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Fatigue † 1  13/171 (7.60%)  25 5/173 (2.89%)  12 11/171 (6.43%)  26 4/31 (12.90%)  5 1/30 (3.33%)  2 2/59 (3.39%)  2 0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Chills † 1  11/171 (6.43%)  26 9/173 (5.20%)  27 5/171 (2.92%)  11 0/31 (0.00%)  0 2/30 (6.67%)  4 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Asthenia † 1  9/171 (5.26%)  11 6/173 (3.47%)  9 5/171 (2.92%)  5 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Injection site pain † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 2/31 (6.45%)  2 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Infections and infestations                   
Nasopharyngitis † 1  17/171 (9.94%)  21 23/173 (13.29%)  30 22/171 (12.87%)  49 2/31 (6.45%)  2 1/30 (3.33%)  1 4/59 (6.78%)  4 0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Upper respiratory tract infection † 1  17/171 (9.94%)  37 13/173 (7.51%)  19 20/171 (11.70%)  34 3/31 (9.68%)  6 1/30 (3.33%)  1 3/59 (5.08%)  3 0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Influenza † 1  9/171 (5.26%)  12 10/173 (5.78%)  17 17/171 (9.94%)  20 2/31 (6.45%)  2 0/30 (0.00%)  0 2/59 (3.39%)  2 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Pharyngitis † 1  9/171 (5.26%)  10 5/173 (2.89%)  9 10/171 (5.85%)  11 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Viral upper respiratory tract infection † 1  9/171 (5.26%)  19 6/173 (3.47%)  12 8/171 (4.68%)  18 1/31 (3.23%)  1 2/30 (6.67%)  7 1/59 (1.69%)  4 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Urinary tract infection † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 2/31 (6.45%)  2 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Rhinitis † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Injury, poisoning and procedural complications                   
Facial bones fracture † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/11 (0.00%) 
Contusion † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/11 (0.00%) 
Fall † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Limb injury † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Investigations                   
Alanine aminotransferase increased † 1  14/171 (8.19%)  15 11/173 (6.36%)  12 5/171 (2.92%)  6 3/31 (9.68%)  3 3/30 (10.00%)  3 3/59 (5.08%)  3 0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Aspartate aminotransferase increased † 1  10/171 (5.85%)  11 9/173 (5.20%)  10 3/171 (1.75%)  3 3/31 (9.68%)  3 1/30 (3.33%)  1 4/59 (6.78%)  4 0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Blood creatine phosphokinase increased † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 3/59 (5.08%)  3 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Anti-thyroid antibody positive † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  1/5 (20.00%)  0/11 (0.00%) 
Musculoskeletal and connective tissue disorders                   
Myalgia † 1  12/171 (7.02%)  21 11/173 (6.36%)  17 8/171 (4.68%)  8 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Pain in extremity † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 0/30 (0.00%)  0 3/59 (5.08%)  6 0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Arthralgia † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
Melanocytic naevus † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/11 (0.00%) 
Nervous system disorders                   
Headache † 1  46/171 (26.90%)  145 37/173 (21.39%)  129 46/171 (26.90%)  135 3/31 (9.68%)  20 2/30 (6.67%)  2 5/59 (8.47%)  14 1/4 (25.00%)  0/5 (0.00%)  2/11 (18.18%) 
Paresthesia † 1  7/171 (4.09%)  16 8/173 (4.62%)  17 16/171 (9.36%)  27 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Cervicobrachial syndrome † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Migraine † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Syncope † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/11 (0.00%) 
Psychiatric disorders                   
Depression † 1  14/171 (8.19%)  17 9/173 (5.20%)  10 10/171 (5.85%)  10 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Anxiety † 1  10/171 (5.85%)  10 7/173 (4.05%)  21 14/171 (8.19%)  20 0/31 (0.00%)  0 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Nervousness † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Reproductive system and breast disorders                   
Vulvovaginal pruritus † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  1/4 (25.00%)  0/5 (0.00%)  0/11 (0.00%) 
Respiratory, thoracic and mediastinal disorders                   
Oropharyngeal pain † 1  6/171 (3.51%)  6 9/173 (5.20%)  13 11/171 (6.43%)  14 2/31 (6.45%)  2 0/30 (0.00%)  0 0/59 (0.00%)  0 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
Skin and subcutaneous tissue disorders                   
Skin irritation † 1  0/171 (0.00%)  0/173 (0.00%)  0/171 (0.00%)  0/31 (0.00%)  0/30 (0.00%)  0/59 (0.00%)  0/4 (0.00%)  0/5 (0.00%)  1/11 (9.09%) 
Vascular disorders                   
Hypertension † 1  0/171 (0.00%)  0 0/173 (0.00%)  0 0/171 (0.00%)  0 0/31 (0.00%)  0 3/30 (10.00%)  3 1/59 (1.69%)  1 0/4 (0.00%)  0/5 (0.00%)  0/11 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor has the right to publish any results communication in connection with the study. The PI shall submit any communications including study results to the sponsor for review 30 working days prior to communication submission. The sponsor can request the PI to modify or delete any sponsor's proprietary information. If the PI refuses the modification, the submission shall be postponed for 60 days from PI refusal, to provide the sponsor the opportunity to file a patent or seek legal remedies.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
Phone: +49-6151-72-5200
EMail: service@merckgroup.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT00404352    
Other Study ID Numbers: IMP27025
2006-002982-38 ( EudraCT Number )
First Submitted: November 27, 2006
First Posted: November 28, 2006
Results First Submitted: May 15, 2012
Results First Posted: September 24, 2012
Last Update Posted: January 24, 2014