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

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®).

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.

Study Overview

• Status: Completed
• Conditions: Relapsing-remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Betaferon/Betaseron; Drug: Betaferon/Betaseron; Drug: Rebif

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.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Aix en Provence, France, 13616
  • Alkirch, France
  • Annecy Cedex, France, 74011
  • Aurillac, France, 15000
  • Belfort, France
  • Blaye, France
  • Bordeaux, France, 33000
  • Boulogne sur Mer, France, 62321
  • Brest Cedex, France
  • Brive La Gaillarde, France, 19100
  • Carcassonne, France
  • Castelnau le Lez, France, 34170
  • Chamaliÿres, France
  • Champigny sur Marne, France
  • Colmar, France
  • Corbeil Essones Cedex, France
  • Créteil, France, 94000
  • Dijon, France
  • Dreux, France
  • Dunkerque, France, 59140
  • Elbeuf, France
  • Evreux Cedex, France, 27023
  • Evry, France
  • La Seyne sur Mer, France, 83500
  • Le Mans, France, 72000
  • Le Mans Cedex, France
  • Libourne Cedex, France, 33505
  • Lille, France
  • Lomme Cedex, France
  • Lyon, France
  • Marseille, France, 13006
  • Montpellier, France
  • Montpellier Cedex 5, France
  • Nancy, France, 54000
  • Nancy Cedex, France
  • Nantes, France, 44000
  • Nice, France
  • Nimes Cedex 9, France, 30900
  • Paris, France
  • Pau, France
  • Perpignan, France, 66000
  • Poissy, France
  • Quimper, France, 29000
  • Quimper, France
  • Quimper Cedex, France
  • Reims, France
  • Rennes, France
  • Rouen, France
  • Rueil Malmaison, France
  • Saint Herblain, France, 44800
  • Saint Quentin, France
  • St Etienne, France
  • St Lÿ, France, 50000
  • St Omer, France, 62505
  • Strasbourg, France
  • Toulouse, France, 31400
  • Tourcoing, France
  • Trelaze, France
  • Vendome, France
  • Vesoul, France, 70000
  • Vichy, France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IFNB-1b 250 mcg (Betaseron) via Betaject; Interferon beta 1b ([IFNB-1b] Betaseron, BAY86-5046) 250 mcg (8 MIU) administered every other days by subcutaneous injection using Betaject	Drug: Betaferon/Betaseron; 250ug administrated with Betaject; Drug: Betaferon/Betaseron; 250ug administrated with Betaject light
Experimental: IFNB-1b 250 mcg (Betaseron) via Betaject light; 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; 250ug administrated with Betaject; Drug: Betaferon/Betaseron; 250ug administrated with Betaject light
Active Comparator: 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	Drug: Rebif; 44ug administered with Rebiject II

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 3 months

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: March 1, 2006
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: April 24, 2006
• First Submitted That Met QC Criteria: April 24, 2006
• First Posted (Estimate): April 25, 2006

Study Record Updates

• Last Update Posted (Estimate): October 21, 2013
• Last Update Submitted That Met QC Criteria: August 15, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; RRMS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Interferon beta-1b
• Other Study ID Numbers: 91489; 2005-005583-91 (EudraCT Number); 308084 (Other Identifier: company internal); Avantage (Other Identifier: company internal)