Safety Study in Relapsing-remitting Multiple Sclerosis (RRMS) Patients Receiving Betaferon or Rebif

Study Overview
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Brief Summary
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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
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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.

Official Title
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The AVANTAGE Study - A Randomized, Multicenter, Phase IV, Open-label Prospective Study Comparing Injection Site Reaction and Injection Site Pain in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) or After a First Demyelinating Event Suggestive of MS Newly Started on Interferon Beta-1b (Betaferon®) or Interferon Beta-1a (Rebif®).

Conditions
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Relapsing-remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Betaferon/Betaseron
* Drug: Rebif
* Drug: Betaferon/Betaseron


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IFNB-1b 250 mcg (Betaseron) via Betaject<br>Interferon beta 1b ([IFNB-1b] Betaseron, BAY86-5046) 250 mcg (8 MIU) administered every other days by subcutaneous injection using Betaject | Drug: Betaferon/Betaseron<br>* 250ug administrated with Betaject<br>|
| Experimental: IFNB-1b 250 mcg (Betaseron) via Betaject light<br>Interferon beta 1b ([IFNB-1b] Betaseron, BAY86-5046) 250 mcg (8 MIU) administered every other days by subcutaneous injection using Betaject Light | Drug: Betaferon/Betaseron<br>* 250ug administrated with Betaject light<br>|
| Active Comparator: IFNB-1a 44 mcg (Rebif) via Rebiject II<br>Interferon beta-1a ([IFNB-1a] Rebif) 44 mcg (12 MIU) three times per week by subcutaneous injection using Rebiject II | Drug: Rebif<br>* 44ug administered with Rebiject II<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Up to 3 months assessed every 24 hours after each injection | 
| 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 | Up to 3 months assessed every 48 hours after each injection | 
| 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 | Up to 3 months assessed every 24 and 48 hours after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Injection Sites With Pain Reported by Physicians |  | Up to 3 months | 
| Percentage of Injection Sites Per Participant With Reaction Reported by Physicians |  | Up to 3 months | 
| Percentage of Participants Without ISR Reported by Participants |  | Up to 3 months assessed every 24 hours after each injection | 
| 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 | Up to 3 months assessed every 24 hours after each injection | 
| 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 | Up to 3 months assessed every 48 hours after each injection | 
| 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 Immediately After Injection | Visual analogue scale was used to report the pain from 0 (no pain ) to 10 (maximal pain). | Immediately after injection | 
| 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). | 30 min after injection | 
| 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). | 1h after injection | 
| 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). | 24h after injection | 
| 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 | 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. | Up to 3 months assessed every 48 hours after each injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, RRMS