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Study To Evaluate The Immunogenicity And Safety Of r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In Multiple Sclerosis

Primary Purpose

Relapsing Remitting Multiple Sclerosis

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Rebif® (clone 484-39)
Sponsored by
Merck KGaA, Darmstadt, Germany
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Remitting Multiple Sclerosis

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Have multiple sclerosis (MS) with two or more relapses in the past two years and is eligible for interferon therapy. Be between 18 and 60 years of age, inclusive. Have given written informed consent, prior to any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care. Be willing and able to follow all study procedures for the duration of the study. Have an Expanded Disability Scale Score (EDSS) less than 6.0 If female, she must either be post menopausal or surgically sterilised; or use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and be neither pregnant nor breast feeding. Confirmation that the subject is not pregnant must be established by a negative SERUM human Chorionic Gonadotrophin (hCG) pregnancy test between 28 to 7 days before Study Day 0.Urine pregnancy test must be done if serum hCG pregnancy test was performed more than 7 days before Study Day 0. A pregnancy test is not required if the subject is post menopausal or surgically sterilised. Exclusion Criteria: Prior Interferon beta therapy (either beta-1b or beta-1a). Major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol. Significant immunosuppressive therapy within the 6 months prior to enrolment. Known history of hypersensitivity to natural or recombinant interferon beta, human serum albumin, or any other component of the formulation. Epilepsy with a history of seizures not adequately controlled by treatment. Have greater than Grade 1 toxicity for liver function tests (Aspartate Transaminase (AST), Alanine Transaminase (ALT), Gamma-Glutamyl Transferase (GGT) or total bilirubin) at the Screening visit Have significant leukopenia (greater than Grade 1 toxicity for total white blood cell count or lymphopenia) at the Screening visit Have had treatment with oral or systemic corticosteroids or Adrenocorticotrophic hormone (ACTH) within 1 month of the Screening visit or between the screening visit and study day 0. Cytokine or anti-cytokine therapy within the 3 months prior to the Screening visit or between the screening visit and study day 0. Use of immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide) within the 6 months prior to the Screening visit or between the screening visit and study day 0. Have taken intravenous immunoglobulin or glatiramer acetate or mitoxantrone or any investigational drug or experimental procedure within the 3 months prior to the Screening visit or between the screening visit and study day 0. Prior use of cladribine or have received total lymphoid irradiation. Presence of systemic disease that might interfere with patient safety, compliance or evaluation of the condition under study (e.g. poorly controlled insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, human immunodeficiency virus (HIV), human T-lymphotrophic virus 1 (HTLV-1)). Other concurrent systemic disorders incompatible with the study (at the Investigator's discretion).

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Rebif® (clone 484-39)

    Arm Description

    Rebif® 44 mcg, three times per week (tiw), subcutaneously (s.c.) During the first 4 weeks of the study, subjects underwent a dose titration regimen of 40% of Rebif® 22 mcg or 20% of Rebif® 44 mcg tiw (8.8 mcg per injection) in the first and second week followed by 100% of Rebif® 22 mcg or 50% of Rebif® 44 mcg (22 mcg per injection) in the third and fourth week. After 4 weeks, subjects received 44 mcg injected s.c. tiw.

    Outcomes

    Primary Outcome Measures

    Number of Participants Testing Positive for Neutralising Antibody (NAb)
    Participants who were NAb+ at 48 weeks (or at the last available NAb assessment up to Week 48). The NAb+ value was defined as NAb ≥ 20 NU/ml.

    Secondary Outcome Measures

    Full Information

    First Posted
    August 21, 2006
    Last Updated
    January 26, 2014
    Sponsor
    Merck KGaA, Darmstadt, Germany
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00367484
    Brief Title
    Study To Evaluate The Immunogenicity And Safety Of r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In Multiple Sclerosis
    Official Title
    Multicentre, Single Arm, Open, Phase IV Study To Evaluate Immunogenicity And Safety Of Subcutaneous r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In The Treatment Of Relapsing Remitting Multiple Sclerosis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    January 2014
    Overall Recruitment Status
    Completed
    Study Start Date
    May 2004 (undefined)
    Primary Completion Date
    January 2006 (Actual)
    Study Completion Date
    January 2006 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck KGaA, Darmstadt, Germany

    4. Oversight

    5. Study Description

    Brief Summary
    The objectives of the study are: - comparison of the incidence and time course of the development of neutralizing antibodies (NAbs) to Rebif after 48 weeks of therapy, to historical data from Serono clinical trial databases to assess the safety and tolerability of Rebif®

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Relapsing Remitting Multiple Sclerosis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    460 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Rebif® (clone 484-39)
    Arm Type
    Experimental
    Arm Description
    Rebif® 44 mcg, three times per week (tiw), subcutaneously (s.c.) During the first 4 weeks of the study, subjects underwent a dose titration regimen of 40% of Rebif® 22 mcg or 20% of Rebif® 44 mcg tiw (8.8 mcg per injection) in the first and second week followed by 100% of Rebif® 22 mcg or 50% of Rebif® 44 mcg (22 mcg per injection) in the third and fourth week. After 4 weeks, subjects received 44 mcg injected s.c. tiw.
    Intervention Type
    Biological
    Intervention Name(s)
    Rebif® (clone 484-39)
    Other Intervention Name(s)
    Recombinant-human interferon beta-1a, r-hIFN Beta-1a
    Intervention Description
    s.c. administered Rebif®
    Primary Outcome Measure Information:
    Title
    Number of Participants Testing Positive for Neutralising Antibody (NAb)
    Description
    Participants who were NAb+ at 48 weeks (or at the last available NAb assessment up to Week 48). The NAb+ value was defined as NAb ≥ 20 NU/ml.
    Time Frame
    48 Weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    60 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Have multiple sclerosis (MS) with two or more relapses in the past two years and is eligible for interferon therapy. Be between 18 and 60 years of age, inclusive. Have given written informed consent, prior to any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care. Be willing and able to follow all study procedures for the duration of the study. Have an Expanded Disability Scale Score (EDSS) less than 6.0 If female, she must either be post menopausal or surgically sterilised; or use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and be neither pregnant nor breast feeding. Confirmation that the subject is not pregnant must be established by a negative SERUM human Chorionic Gonadotrophin (hCG) pregnancy test between 28 to 7 days before Study Day 0.Urine pregnancy test must be done if serum hCG pregnancy test was performed more than 7 days before Study Day 0. A pregnancy test is not required if the subject is post menopausal or surgically sterilised. Exclusion Criteria: Prior Interferon beta therapy (either beta-1b or beta-1a). Major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol. Significant immunosuppressive therapy within the 6 months prior to enrolment. Known history of hypersensitivity to natural or recombinant interferon beta, human serum albumin, or any other component of the formulation. Epilepsy with a history of seizures not adequately controlled by treatment. Have greater than Grade 1 toxicity for liver function tests (Aspartate Transaminase (AST), Alanine Transaminase (ALT), Gamma-Glutamyl Transferase (GGT) or total bilirubin) at the Screening visit Have significant leukopenia (greater than Grade 1 toxicity for total white blood cell count or lymphopenia) at the Screening visit Have had treatment with oral or systemic corticosteroids or Adrenocorticotrophic hormone (ACTH) within 1 month of the Screening visit or between the screening visit and study day 0. Cytokine or anti-cytokine therapy within the 3 months prior to the Screening visit or between the screening visit and study day 0. Use of immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporin, methotrexate, azathioprine, linomide) within the 6 months prior to the Screening visit or between the screening visit and study day 0. Have taken intravenous immunoglobulin or glatiramer acetate or mitoxantrone or any investigational drug or experimental procedure within the 3 months prior to the Screening visit or between the screening visit and study day 0. Prior use of cladribine or have received total lymphoid irradiation. Presence of systemic disease that might interfere with patient safety, compliance or evaluation of the condition under study (e.g. poorly controlled insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, human immunodeficiency virus (HIV), human T-lymphotrophic virus 1 (HTLV-1)). Other concurrent systemic disorders incompatible with the study (at the Investigator's discretion).
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Bettina Stubinski, M.D.
    Organizational Affiliation
    Merck Serono SA - Geneva
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Links:
    URL
    http://www.mslifelines.com
    Description
    Full FDA approved prescribing information can be found here

    Learn more about this trial

    Study To Evaluate The Immunogenicity And Safety Of r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In Multiple Sclerosis

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