Phase 3
Completed N=300
Long-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX)
Source: ClinicalTrials.gov NCT00813709 ↗Enrolled (actual)
300
Serious AEs
7.0%
Results posted
Oct 2013
Primary outcomePrimary: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months — 41.3; 27.6; 27.1 Cumulative % of participants with CDMS — p=0.002
Summary
REFLEXION is a double blind extension of the study 27025 (NCT00404352) (REFLEX). The purpose of the study is to obtain long-term follow-up data in subjects with clinically definite multiple sclerosis (MS) and subjects with a first demyelinating event at high risk of converting to MS, treated with fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months |
41.3; 27.6; 27.1 | 0.002 sig |
| SECONDARY Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 Months |
7.5; 11.8; 13.2 | 0.205 |
| SECONDARY Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Lesions Per Participant Per Scan at Month 36 |
1.02; 1.83; 1.63; 0.83; 1.39; 1.19 | — |
| SECONDARY Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36 |
670.3; 774.8; 675.0; 303.2; 272.0; 133.3 | — |
| SECONDARY Percent Change From Baseline in Brain Volume at Month 36 |
-1.02; -0.86; -1.14 | — |
| SECONDARY Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months |
84.2; 76.0; 66.7 | — |
| SECONDARY Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36 |
0.0358; -0.0909; 0.0031; 0.3483; 0.5044; 0.4515 | — |
| SECONDARY Percentage of Relapse-Free Participants at Month 36 |
42.7; 58.3; 51.5 | — |
| SECONDARY Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36 |
1.53; 1.50; 1.51; -0.21; -0.11; -0.09 | — |
| SECONDARY Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36 |
0.0352; 0.0071; -0.0575; 0.1993; 0.2529; 0.3074 | — |
| SECONDARY Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36 |
77; 97; 88; 41; 34; 30 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation |
70; 96; 84; 7; 7; 9 | — |
| SECONDARY Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to Month 60 |
44.6; 40.7; 39.2 | — |
| SECONDARY Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months |
11.0; 18.7; 18.4 | — |
| SECONDARY Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New T1 Lesions Per Participant Per Scan at Month 60 |
1.46; 1.60; 1.94; 1.17; 1.17; 1.35 | — |
| SECONDARY Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60 |
670.3; 774.8; 675.0; 415.0; 412.3; 261.8 | — |
| SECONDARY Percent Change From Baseline in Brain Volume at Month 60 |
-1.82; -1.54; -2.03 | — |
| SECONDARY Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60 |
84.2; 82.9; 72.5 | — |
| SECONDARY Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60 |
0.0358; -0.0909; 0.0031; 0.4109; 0.4785; 0.4608 | — |
| SECONDARY Percentage of Relapse-Free Participants at Month 60 |
34.5; 45.1; 40.9 | — |
| SECONDARY Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60 |
1.53; 1.50; 1.51; -0.11; -0.01; 0.04 | — |
| SECONDARY Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60 |
0.0352; 0.0071; -0.0575; 0.2290; 0.2213; 0.2192 | — |
| SECONDARY Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60 |
89; 99; 100; 25; 30; 15 | — |
| SECONDARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation |
70; 96; 84; 7; 7; 9 | — |
Eligibility Criteria
Inclusion Criteria
- Reach scheduled end of study in Study 27025 (REFLEX) (completion of 24 months participation)
- Medical assessment by the Investigator/treating physician from study 27025 that there is no objection to the subject's participation in this extension trial considering the medical experience from Study 27025 (REFLEX). Special attention should be given to laboratory abnormalities and clinically significant liver, renal and bone-marrow dysfunction
- If female, subject must:
- be neither pregnant nor breast-feeding, nor attempting to conceive
- use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (that is [i.e.] less than 1 percent [%] per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner
- Subject is willing to follow study procedures
- Subject has given written informed consent
Exclusion Criteria
- Subject has any disease other than MS that could better explain the subject's signs and symptoms
- Subject has a primary progressive course of MS
- Subject has total bilirubin greater than 2.5 times upper limit of normal (ULN) at both Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalization of the value)
- Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN values at both Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalization of the value)
- Subject suffers from another current autoimmune disease
- Subject suffers from major medical or psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
- Subject has a history of seizures not adequately controlled by treatment
- Subject has cardiac disease, such as angina, congestive heart failure or arrhythmia
- Subject has a known allergy to IFN-beta or the excipient(s) of the study medication
- Subject has any condition that could interfere with the MRI evaluation
- Subject has a known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
- Subject has a history of alcohol or drug abuse
- Subject has previously participated in this study
- Subject has moderate to severe renal impairment
- Subject is pregnant or lactating
- Subject has any medical, psychiatric or other conditions that compromise his/her ability to understand the subject information, to give informed consent, to comply with the study protocol, or to complete the study
Data sourced from ClinicalTrials.gov (NCT00813709). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.