Clinically Isolated Syndrome
Conditions
Brief summary
The primary objective of this initiative is to assess the effectiveness of subcutaneous (sc) interferon (IFN) beta - 1a, (Rebif®), versus No Treatment in delaying the conversion to Clinically Definite Multiple Sclerosis (CDMS) - as defined by the occurrence of a second exacerbation - over 96 weeks in subjects that present with Clinically Isolated Syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI). The secondary objectives are to: * Assess the effectiveness of sc IFN beta - 1a (Rebif®) therapy in reducing the proportion of patients with CIS converting to CDMS * Assess the safety of sc IFN beta - 1a (Rebif®) in the patients with CIS
Interventions
DRUGRebif®
44 microgram (mcg) IFN beta-1a sc once a week (qw) for 96 weeks
OTHERNo Treatment
No treatment for 96 weeks
Sponsors
EMD Serono Canada Inc.
Merck KGaA, Darmstadt, Germany
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject must have experienced a first clinical episode suggestive of demyelinating disease * Subject must present with an abnormal MRI displaying at least 3 T2 weighted hyperintense lesions typical of multiple sclerosis (MS) * Subject must be greater than or equal to 18 years old * Subject must have had onset of the clinical attack within the last 120 days * Subject must give written informed consent * Female subjects must be neither pregnant nor breast feeding, and must not be of child-bearing potential as defined by either: * Being post-menopausal or surgically sterile * Using hormonal contraceptive, intra-uterine device, diaphragm with spermicide or condom with spermicide for the duration of the study Subjects electing treatment: * Subject must be eligible for Interferon-beta 1-a therapy
Exclusion criteria
* Subject has evidence of other neurological diseases that could explain his/her symptomatology * Subject is pregnant or in lactation * Subject suffers from an intercurrent autoimmune disease * Subject suffers from major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the procedures required by this study * Subject has received immunomodulatory or immunosuppressive therapy (including but not limited to cyclophosphamide, cyclosporine, methotrexate, azathioprine, linomide, mitoxantrone, teriflunomide, natalizumab, laquinimod, campath), within 12 months of study day 1 Subjects electing treatment: * Subject has inadequate liver function, defined by total bilirubin, aspartate transaminase (AST), alanine aminotransferase (ALT), or alkaline phosphatase \> 2.5 times the upper limit of normal values * Subject has inadequate bone marrow reserve, defined as white blood cell count less than 0.5 times the lower limit of normal * Subject has a known allergy to IFN or any of the excipients of the drug product
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in Month to Clinical Definite Multiple Sclerosis (CDMS) From Kaplan-Meier Estimates | Up to Week 96 | CDMS was defined by the occurrence of a second exacerbation or relapse over 96 weeks in participants who presented with Clinically Isolated Syndrome (CIS) accompanied by an abnormal Magnetic Resonance Imaging (MRI) scan. Time was calculated from the date of the stabilization of the baseline CIS episode to the qualifying relapse for the CDMS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Converted to Clinical Definite Multiple Sclerosis (CDMS) | Up to Week 96 | CDMS was defined as the occurrence of a second exacerbation over 96 weeks in participants who presented with CIS accompanied by an abnormal MRI scan. |
| Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | Up to Week 96 | AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rebif 44 Mcg Rebif was administered subcutaneously (sc) at a dose of 44 microgram (mcg) once weekly. | 32 |
| No Treatment Participants in this group did not receive any treatment. | 3 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 0 |
| Overall Study | Non-qualifying relapse | 1 | 0 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Qualifying relapse | 12 | 1 |
Baseline characteristics
| Characteristic | Rebif 44 Mcg | No Treatment | Total |
|---|---|---|---|
| Age, Continuous | 36.30 years STANDARD_DEVIATION 9.68 | 35.30 years STANDARD_DEVIATION 13.32 | 35.80 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 19 Participants | 3 Participants | 22 Participants |
| Sex: Female, Male Male | 13 Participants | 0 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 32 / 32 | 0 / 0 |
| serious Total, serious adverse events | 1 / 32 | 0 / 0 |
Outcome results
Primary
Time in Month to Clinical Definite Multiple Sclerosis (CDMS) From Kaplan-Meier Estimates
CDMS was defined by the occurrence of a second exacerbation or relapse over 96 weeks in participants who presented with Clinically Isolated Syndrome (CIS) accompanied by an abnormal Magnetic Resonance Imaging (MRI) scan. Time was calculated from the date of the stabilization of the baseline CIS episode to the qualifying relapse for the CDMS.
Time frame: Up to Week 96
Population: Intent-to-treat (ITT) population: All participants in Treatment group who received at least 1 dose of Rebif® and all participants in observational group who had at least 1 post-baseline visit were included in ITT population. Two participants had negative time from stabilization and CDMS relapse and were excluded from the Kaplan-Meier analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rebif 44 Mcg | Time in Month to Clinical Definite Multiple Sclerosis (CDMS) From Kaplan-Meier Estimates | 15.6 Month | Standard Error 1.23 |
| No Treatment | Time in Month to Clinical Definite Multiple Sclerosis (CDMS) From Kaplan-Meier Estimates | 17.0 Month | — |
Secondary
Percentage of Participants Who Converted to Clinical Definite Multiple Sclerosis (CDMS)
CDMS was defined as the occurrence of a second exacerbation over 96 weeks in participants who presented with CIS accompanied by an abnormal MRI scan.
Time frame: Up to Week 96
Population: Intent-to-treat (ITT) population: All participants in Treatment group who received at least 1 dose of Rebif® and all participants in observational group who had at least 1 post-baseline visit were included in ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rebif 44 Mcg | Percentage of Participants Who Converted to Clinical Definite Multiple Sclerosis (CDMS) | 37.5 Percentage of participants |
| No Treatment | Percentage of Participants Who Converted to Clinical Definite Multiple Sclerosis (CDMS) | 33.3 Percentage of participants |
Secondary
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.
Time frame: Up to Week 96
Population: Intent-to-treat (ITT) population: All participants in Treatment group who received at least 1 dose of Rebif® and all participants in observational group who had at least 1 post-baseline visit were included in ITT population. Adverse events were not captured for No Treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rebif 44 Mcg | Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs) | 100 percentage of participants |