Relapsing-remitting Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, RRMS
Brief summary
The purpose of this study is to compare the injection site reaction and injection site pain after subcutaneous administration of either Betaferon 250µg or Rebif 44µg using different autoinjectors.
Detailed description
Original French title of the study: Etude de phase IV, multicentrique, randomisée, ouverte, comparant les réactions et la douleur aux sites d'injection après administration sous-cutanée d'interféron β-1b (Betaferon®) ou interféron β-1a (Rebif®) pendant la période de trois mois d'initiation de la thérapie chez des patients atteints d'une forme récurrente/rémittente de sclérose en plaques. The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare AG, Germany. Bayer HealthCare AG, Germany is the sponsor of the trial.
Interventions
250ug administrated with Betaject
DRUGRebif
44ug administered with Rebiject II
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Males or females * Age \>= 18 years old * Patients after a first demyelinating event suggestive of MS (only for Betaferon) as well as patients with a definite diagnosis of RRMS (Betaferon et Rebif) * First justified prescription of one interferon beta by subcutaneous route (as described in Summary of Product Characteristics \[SmPC\] of Betaferon or Rebif) * Females of child-bearing potential must agree to practice adequate contraceptive methods over the duration of the study (not applicable for men) * Patient can follow and comply with all study procedures of the trial protocol * Laboratory evaluations (i.e., evaluation of hepatic enzyme gamma-GT, full blood count and differential white blood cell count \[WBC\]) must be available and the results must be normal. * Written informed consent
Exclusion criteria
* Any contraindication to the prescription of Betaferon or Rebif, as described in the SmPC of products: * Pregnancy or lactation * Known hypersensitivity to natural or recombinant interferon beta, to mannitol, to human albumin or any other excipients used * History of severe depression or suicide attempt or current suicidal ideation. * Patient with decompensated liver disease * Epilepsy not adequately controlled by treatment * Patient previously included in this study. * Patient previously treated by sub-cutaneous route with either Betaferon or Rebif. * Participation in any clinical trial within the past 30 days involving the investigational drug intake. * Medical, psychiatric or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol or to complete the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Scores of Reaction After Injection Reported by Participants | Up to 3 months assessed every 24 and 48 hours after injection | Score range is: 0 - no abnormal reaction, 1 -erythema, 2-edema, 3-infiltration, 4-ulceration or necrosis |
| Percentage of the Sites Developing a Injection Site Reaction (ISR) Reported by Participants 24 Hours After Each Injection | Up to 3 months assessed every 24 hours after each injection | An injection site is seen as developing a reaction if the patient's score for this site is of a reaction intensity ≥ 1. Number of injection sites per month per participant analyzed |
| Percentage of Sites Developing a Injection Site Reaction (ISR) Reported by Participants 48 Hours After Each Injection | Up to 3 months assessed every 48 hours after each injection | An injection site is seen as developing a reaction if the patient's score for this site is of a reaction intensity ≥ 1. Number of injection sites per month per participant analyzed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Injection Sites Per Participant With Reaction Reported by Physicians | Up to 3 months | — |
| Percentage of Sites Developing a Severe Reaction 24 Hours After Injection | Up to 3 months assessed every 24 hours after each injection | An ISR is considered as severe if the score reported by the patient is above 2 (at least one red skin) 0- no abnormal reaction, 1- erythema, 2-edema, 3- infiltration 4- ulceration or necrosis |
| Percentage of Sites Developing a Severe Reaction 48 Hours After Injection | Up to 3 months assessed every 48 hours after each injection | An ISR is considered as severe if the score reported by the patient is above 2 (at least one red skin) 0- no abnormal reaction, 1- erythema, 2-edema, 3- infiltration 4- ulceration or necrosis |
| Percentage of Participants Without Pain Reported by Participants | Up to 3 months assessed 24 hours after each injection | — |
| Percentage of Injection Sites Without Pain Reported by Physicians | Up to 3 months | — |
| Percentage of Injection Sites Without Pain Reported by Participants | Up to 3 months assessed 24 hours after each injection | — |
| Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 30 Minutes After Injection | 30 min after injection | Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain). |
| Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 1 Hour After Injection | 1h after injection | Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain). |
| Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 24 Hours After Injection | 24h after injection | Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain). |
| Percentage of Sites Without Reaction 24 Hours After Injection Reported by Participants | Up to 3 months assessed every 24 hours after each injection | — |
| Percentage of Sites Without Reaction 48 Hours After Injection Reported by Participants | Up to 3 months assessed every 48 hours after each injection | if the patient score is missing, at the injection site, then the patient is not considered without or with developping reaction. An injection site is seen as developing no reaction if the patient's score for this site is of a reaction intensity = 0. |
| Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants Immediately After Injection | Immediately after injection | Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain). |
| Percentage of Participants Without ISR Reported by Participants | Up to 3 months assessed every 24 hours after each injection | — |
| Percentage of Injection Sites With Pain Reported by Physicians | Up to 3 months | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Scores of Reaction After Injection Reported by Patients Between Different Auto Injectors | Up to 3 months | Score range is: 0 - no abnormal reaction, 1 -erythema, 2-edema, 3-infiltration, 4-ulceration or necrosis |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IFNB-1b 250 Mcg (Betaseron) Interferon beta 1b (\[IFNB-1b\] Betaseron, BAY86-5046) 250 mcg (8 MIU) administered every other days by subcutaneous injection using Betaject or Betaject Light | 142 |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II Interferon beta-1a (\[IFNB-1a\] Rebif) 44 mcg (12 MIU) three times per week by subcutaneous injection using Rebiject II | 63 |
| Total | 205 |
Baseline characteristics
| Characteristic | IFNB-1b 250 Mcg (Betaseron) | IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Total |
|---|---|---|---|
| Age Continuous | 39.2 Years STANDARD_DEVIATION 10.3 | 38.4 Years STANDARD_DEVIATION 10.5 | 38.7 Years STANDARD_DEVIATION 10.4 |
| Expanded disability status scale at screening (EDSS) | 1.7 Scores on a scale STANDARD_DEVIATION 1.2 | 1.9 Scores on a scale STANDARD_DEVIATION 1.4 | 1.8 Scores on a scale STANDARD_DEVIATION 1.3 |
| Number of relapses | 2.2 Relapses STANDARD_DEVIATION 1.2 | 2.1 Relapses STANDARD_DEVIATION 1 | 2.1 Relapses STANDARD_DEVIATION 1.1 |
| Sex: Female, Male Female | 106 Participants | 47 Participants | 153 Participants |
| Sex: Female, Male Male | 36 Participants | 16 Participants | 52 Participants |
| Time since diagnosis | 3.3 Years STANDARD_DEVIATION 5.7 | 3.3 Years STANDARD_DEVIATION 6.7 | 3.3 Years STANDARD_DEVIATION 6.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 83 / 150 | 42 / 65 |
| serious Total, serious adverse events | 2 / 150 | 1 / 65 |
Outcome results
Primary
Mean Scores of Reaction After Injection Reported by Participants
Score range is: 0 - no abnormal reaction, 1 -erythema, 2-edema, 3-infiltration, 4-ulceration or necrosis
Time frame: Up to 3 months assessed every 24 and 48 hours after injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Mean Scores of Reaction After Injection Reported by Participants | 0.368 Scores on a scale | Standard Deviation 3.11 |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Scores of Reaction After Injection Reported by Participants | 0.500 Scores on a scale | Standard Deviation 3.45 |
Primary
Percentage of Sites Developing a Injection Site Reaction (ISR) Reported by Participants 48 Hours After Each Injection
An injection site is seen as developing a reaction if the patient's score for this site is of a reaction intensity ≥ 1. Number of injection sites per month per participant analyzed
Time frame: Up to 3 months assessed every 48 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Sites Developing a Injection Site Reaction (ISR) Reported by Participants 48 Hours After Each Injection | 27 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Sites Developing a Injection Site Reaction (ISR) Reported by Participants 48 Hours After Each Injection | 41 Percentage of sites |
Primary
Percentage of the Sites Developing a Injection Site Reaction (ISR) Reported by Participants 24 Hours After Each Injection
An injection site is seen as developing a reaction if the patient's score for this site is of a reaction intensity ≥ 1. Number of injection sites per month per participant analyzed
Time frame: Up to 3 months assessed every 24 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of the Sites Developing a Injection Site Reaction (ISR) Reported by Participants 24 Hours After Each Injection | 31 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of the Sites Developing a Injection Site Reaction (ISR) Reported by Participants 24 Hours After Each Injection | 37 Percentage of sites |
Secondary
Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 1 Hour After Injection
Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain).
Time frame: 1h after injection
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 1 Hour After Injection | 0.5737 Scores on a scale |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 1 Hour After Injection | 0.6666 Scores on a scale |
Secondary
Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 24 Hours After Injection
Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain).
Time frame: 24h after injection
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 24 Hours After Injection | 0.6411 Scores on a scale |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 24 Hours After Injection | 0.5811 Scores on a scale |
Secondary
Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 30 Minutes After Injection
Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain).
Time frame: 30 min after injection
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 30 Minutes After Injection | 0.7046 Scores on a scale |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants 30 Minutes After Injection | 0.8461 Scores on a scale |
Secondary
Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants Immediately After Injection
Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain).
Time frame: Immediately after injection
| Arm | Measure | Value (MEAN) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants Immediately After Injection | 1.1992 Scores on a scale |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Pain Assessment Using Visual Analogue Scale (VAS) Reported by Participants Immediately After Injection | 1.4502 Scores on a scale |
Secondary
Percentage of Injection Sites Per Participant With Reaction Reported by Physicians
Time frame: Up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Injection Sites Per Participant With Reaction Reported by Physicians | 14.1 Percentage of ISR |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Injection Sites Per Participant With Reaction Reported by Physicians | 18.6 Percentage of ISR |
Secondary
Percentage of Injection Sites Without Pain Reported by Participants
Time frame: Up to 3 months assessed 24 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Injection Sites Without Pain Reported by Participants | 30.3 Percentage of injection sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Injection Sites Without Pain Reported by Participants | 42.0 Percentage of injection sites |
Secondary
Percentage of Injection Sites Without Pain Reported by Physicians
Time frame: Up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Injection Sites Without Pain Reported by Physicians | 85.9 Percentage of injection sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Injection Sites Without Pain Reported by Physicians | 81.4 Percentage of injection sites |
Secondary
Percentage of Injection Sites With Pain Reported by Physicians
Time frame: Up to 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Injection Sites With Pain Reported by Physicians | 6.2 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Injection Sites With Pain Reported by Physicians | 5.2 Percentage of sites |
Secondary
Percentage of Participants Without ISR Reported by Participants
Time frame: Up to 3 months assessed every 24 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Participants Without ISR Reported by Participants | 21.3 Percentage of participants |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Participants Without ISR Reported by Participants | 9.5 Percentage of participants |
Secondary
Percentage of Participants Without Pain Reported by Participants
Time frame: Up to 3 months assessed 24 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Participants Without Pain Reported by Participants | 5.6 Percentage of participants |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Participants Without Pain Reported by Participants | 17.7 Percentage of participants |
Secondary
Percentage of Sites Developing a Severe Reaction 24 Hours After Injection
An ISR is considered as severe if the score reported by the patient is above 2 (at least one red skin) 0- no abnormal reaction, 1- erythema, 2-edema, 3- infiltration 4- ulceration or necrosis
Time frame: Up to 3 months assessed every 24 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Sites Developing a Severe Reaction 24 Hours After Injection | 6.1 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Sites Developing a Severe Reaction 24 Hours After Injection | 8.45 Percentage of sites |
Secondary
Percentage of Sites Developing a Severe Reaction 48 Hours After Injection
An ISR is considered as severe if the score reported by the patient is above 2 (at least one red skin) 0- no abnormal reaction, 1- erythema, 2-edema, 3- infiltration 4- ulceration or necrosis
Time frame: Up to 3 months assessed every 48 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Sites Developing a Severe Reaction 48 Hours After Injection | 4.97 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Sites Developing a Severe Reaction 48 Hours After Injection | 8.76 Percentage of sites |
Secondary
Percentage of Sites Without Reaction 24 Hours After Injection Reported by Participants
Time frame: Up to 3 months assessed every 24 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Sites Without Reaction 24 Hours After Injection Reported by Participants | 62.2 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Sites Without Reaction 24 Hours After Injection Reported by Participants | 63.0 Percentage of sites |
Secondary
Percentage of Sites Without Reaction 48 Hours After Injection Reported by Participants
if the patient score is missing, at the injection site, then the patient is not considered without or with developping reaction. An injection site is seen as developing no reaction if the patient's score for this site is of a reaction intensity = 0.
Time frame: Up to 3 months assessed every 48 hours after each injection
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Percentage of Sites Without Reaction 48 Hours After Injection Reported by Participants | 71.8 Percentage of sites |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Percentage of Sites Without Reaction 48 Hours After Injection Reported by Participants | 54.6 Percentage of sites |
Other Pre-specified
Mean Scores of Reaction After Injection Reported by Patients Between Different Auto Injectors
Score range is: 0 - no abnormal reaction, 1 -erythema, 2-edema, 3-infiltration, 4-ulceration or necrosis
Time frame: Up to 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFNB-1b 250 Mcg (Betaseron) | Mean Scores of Reaction After Injection Reported by Patients Between Different Auto Injectors | 0.372 Scores on a scale | Standard Deviation 2.82 |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Scores of Reaction After Injection Reported by Patients Between Different Auto Injectors | 0.363 Scores on a scale | Standard Deviation 3.34 |
| IFNB-1a 44 Mcg (Rebif) Via Rebiject II | Mean Scores of Reaction After Injection Reported by Patients Between Different Auto Injectors | 0.5 Scores on a scale | Standard Deviation 3.45 |