Relapsing Remitting Multiple Sclerosis
Conditions
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®
Interventions
BIOLOGICALRebif® (clone 484-39)
s.c. administered Rebif®
Sponsors
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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prior to any study related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to their future medical care.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 1. be post menopausal or surgically sterilised; or 2. use a hormonal contraceptive, intra uterine device, diaphragm with spermicide, or condom with spermicide, for the duration of the study; and 3. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Testing Positive for Neutralising Antibody (NAb) | 48 Weeks | 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. |
Participant flow
Recruitment details
Subjects were screened for enrollment from 27 May 2004 and attended the last visit on 30 January 2006. Four hundred and eighty four subjects were screened for enrollment and 460 were enrolled. Two subjects (0.4%) were excluded from the ITT Population since they had no post-Baseline NAb assessment due to withdrawing from the study prematurely.
Pre-assignment details
At Week -4 (to Week -1), subjects provided written informed consent and underwent screening procedures. Twenty four subjects were not included in the study: the reasons were Not met all eligibility criteria (18 subjects) and Other (6 subjects)
Participants by arm
| Arm | Count |
|---|---|
| Rebif® (Clone 484-39) subcutaneously administered Rebif® 44mcg three times per week | 458 |
| Total | 458 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | The choice of the patient | 1 |
| Overall Study | Travel to USA | 1 |
| Overall Study | Withdrew informed consent | 5 |
Baseline characteristics
| Characteristic | Rebif® (Clone 484-39) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 458 Participants |
| Age, Continuous | 36.0 years STANDARD_DEVIATION 8.9 |
| Neutralising Antibody (NAb) Status | 458 Participants not testing NAb positive |
| Region of Enrollment Estonia | 36 participants |
| Region of Enrollment France | 2 participants |
| Region of Enrollment Hungary | 23 participants |
| Region of Enrollment Lithuania | 69 participants |
| Region of Enrollment Morocco | 5 participants |
| Region of Enrollment Poland | 69 participants |
| Region of Enrollment Romania | 87 participants |
| Region of Enrollment Russian Federation | 43 participants |
| Region of Enrollment Serbia | 80 participants |
| Region of Enrollment Tunisia | 31 participants |
| Region of Enrollment United Kingdom | 13 participants |
| Sex: Female, Male Female | 336 Participants |
| Sex: Female, Male Male | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 378 / 460 |
| serious Total, serious adverse events | 11 / 460 |
Outcome results
Primary
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.
Time frame: 48 Weeks
Population: Intent To Treat (ITT) population, Last Observation Carried Forward (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rebif® (Clone 484-39) | Number of Participants Testing Positive for Neutralising Antibody (NAb) | 73 NAb+ participants |