BEYOND Follow-up: Betaferon®/Betaseron® Efficacy Yielding Outcomes of a New Dose

Study Overview
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Brief Summary
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The BEYOND Follow-Up study will give patients who participated in the preceding BEYOND study the opportunity to continue treatment with the 500µg dose of interferon beta (IFNB) 1b and will further investigate the safety and tolerability profile of interferon beta 1b 500µg during longer-term treatment.

Detailed Description
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Phase A (3 arm parallel group): All patients randomized during the BEYOND study (Bayer 306440) to either IFNB 1b group (250µg or 500µg) will continue their previously assigned study medication, applying the same level of blinding as during the BEYOND study, All patients randomized during the BEYOND study to Copaxone and all patients with premature discontinuation of study medication during the BEYOND study will receive open-label IFNB 1b 250µg. Phase B (single arm): All patients will receive open-label IFNB 1b 500µg) Randomization: No randomization in this trial, patient's allocation in this follow-up study depends only on prior trial groups. The preceding study was randomized. The trial is sponsored by Bayer Schering Pharma AG, Germany, Bayer HealthCare and Bayer HealthCare Pharmaceuticals Inc. Secondary outcome measure Assessment of patient-reported outcomes (FAMS and EQ 5D: The variables FAMS and EQ-5D were not analyzed due to the termination of the study before start of Phase B.

Official Title
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International, Multicenter, Phase IIIb Study of Subcutaneous Every-other-day Treatment of Patients With Relapsing Multiple Sclerosis With (Phase A): Double-blind Betaseron/Betaferon 250µg or 500µg or Open-label Betaseron/Betaferon 250µg and (Phase B): Open-label Betaseron/Betaferon 500µg

Conditions
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Multiple Sclerosis, Relapsing-Remitting

Intervention / Treatment
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* Drug: Interferon beta-1b (Betaseron, BAY86-5046)
* Drug: Interferon beta-1b (Betaseron, BAY86-5046)
* Drug: Interferon beta-1b (Betaseron, BAY86-5046)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completion of the BEYOND study 306440 as scheduled Relapsing multiple sclerosis Medical assessment by the investigator that there is no objection to the patient's participation in this trial considering the medical experience from study 306440. Special attention should be given to laboratory abnormalities and clinically relevant liver, renal and bone-marrow dysfunction. Females of child-bearing potential: Agreement to practice adequate contraception methods and Negative pregnancy test and No lactation Written informed consent Exclusion Criteria: Serious or acute heart diseases History of severe depression or suicide attempt Epilepsy not adequately controlled by treatment Known allergy to IFNs, to human albumin or to mannitol 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IFNB-1b 500 mcg<br>Interferon beta 1b ([IFNB 1b] Betaseron) 500 mcg administered s.c. every other day (double blind) | Drug: Interferon beta-1b (Betaseron, BAY86-5046)<br>* Phase A: 500ug administrated s.c. every other day (double blind). For patients previously randomized in Bayer study 91162 to the same treatment. Phase B: All patients will receive 500µg s.c.every other day (open-label).<br>|
| Experimental: IFNB-1b 250 mcg<br>Interferon beta 1b ([IFNB 1b] Betaseron) 250 mcg administered s.c. every other day (double blind) | Drug: Interferon beta-1b (Betaseron, BAY86-5046)<br>* Phase A: 250ug administrated s.c. every other day (double blind). For patients previously randomized in Bayer study 91162 to the same treatment. Phase B: All patients will receive 500µg s.c.every other day (open-label).<br>|
| Experimental: IFNB-1b 250 mcg*<br>Interferon beta 1b ([IFNB 1b] Betaseron) 250 mcg administered s.c. every other day *(Subjects who were administered Copaxone and subjects who had prematurely discontinued medication during BEYOND study.) | Drug: Interferon beta-1b (Betaseron, BAY86-5046)<br>* Phase A: 250ug administrated s.c. every other day (open-label). For patients previously randomized in Bayer study 91162 to 20mg Copaxone® administrated s.c. once daily and patients with premature discontinuation of study medication during the study 91162. Phase B: All patients will receive 500µg s.c.every other day (open-label).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Flu-like-syndrome | The variable Flu-like-syndrome will consist of a combination of MedDRA terms (Preferred Terms and Lower Level Terms) indicative for this condition. | 309 days | 
| Injection-site Reactions | The variable Injection-site reactions will consist of a combination of MedDRA terms (Preferred Terms only) indicative for this condition. | 309 days | 
| Liver Enzyme Elevations | The variable Liver enzyme elevations will consist of a combination of MedDRA terms (Preferred Terms only) indicative for this condition. | 309 days | 
| Hematological Abnormalities | The variable Hematological abnormalities will consist of a combination of MedDRA terms (Preferred Terms only) indicative for this condition. | 309 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Neutralizing Antibody Titer to IFNB-1b of Different Cut-off Values | Serum samples of about 8 mL for analysis of neutralizing antibodies (NAbs) to interferon (IFN) beta-1b were drawn at Baseline, Week 26 and the EOS visit. | 309 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relapsing multiple sclerosis, interferon beta 1b, Betaferon, Betaseron