Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Relapsing, Interferon beta 1a, Curcumin
Brief summary
This is a prospective, monocentric, double blind, placebo controlled, two arm study. Curcumin is derived from the rhizomes of the plant Curcuma longa (common name, turmeric) belonging to the Zingiberaceae family found in South Asian countries, especially India which is the largest producer. BCM95 (bioCurcumin) is a combination of a Curcumin extract and oil to enhance the bio-absorbability in humans. BCM95 may enhance and prolong the antioxidant and anti-inflammatory effects of the standard therapy maintaining a good safety profile.
Detailed description
The subjects must experience at least one Gadolinium (GD) enhancing Magnetic Resonance Imaging (MRI) lesion at the baseline visit or one Multiple Sclerosis (MS) relapse in the last 6 months before the screening visit. Randomization, in a 1:1 ratio, will be done with two arms: 40 subjects with Interferon (IFN) beta 1 a 44 mcg TIW + Curcumin (BCM 95) and 40 subjects with IFN beta-1a 44 mcg TIW + placebo. The study will last 42 months: 18 months of enrolment and 24 months of treatment period. The study consists of 6 visits per subject: screening visit (Visit 0), baseline (Visit 1), a visit 3 months after baseline (Visit 2), 6 months after baseline (Visit 3), 12 months after baseline (Visit 4) and 24 months after baseline (Visit 5).
Interventions
DRUGIFN beta 1a 44 mcg TIW
Subjects received IFN beta 1a 44 microgram (mcg) subcutaneously TIW for 24 months.
DRUGCurcumin
Subjects received 500 milligram (mg) curcumin orally twice a day for 24 months.
DRUGPlacebo
Subjects received placebo matched to curcumin orally twice a day for 24 months.
Sponsors
Merck Serono S.P.A., Italy
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Subjects with early diagnosis (no more than 3 years) of Relapsing Multiple Sclerosis according to the revised McDonald Criteria (2010) * Subjects currently in treatment with IFN beta-1a 44 mcg TIW, having received this treatment a minimum of 6 months and for not longer than 12 months before enrollment. * Subjects must experience at least one Gd-enhancing MRI lesion at baseline visit or one MS relapse in the last 6 months before screening visit. * Males and females between 18 - 60 years of age * Subjects with Expanded Disability Status Scale (EDSS) between 0-5.5 * No use of oral or systemic corticosteroids or corticotropin (ACTH) within 30 days prior to Screening visit. No use of any Disease Modifying Drug (DMD) (other than IFN beta-1a 44 mcg) 12 months prior to Screening visit * Be willing and able to comply with the protocol * Signed informed consent
Exclusion criteria
* Pregnancy and breast-feeding * History of alcohol or drug abuse * Serious psychiatric disorders * History or presence of serious or acute gastrointestinal disease such as gastric or duodenal ulcer, ulcerative colitis and inflammatory bowel or Crohn's disease * Subjects suffering by obstruction of the biliary tract * Any major medical condition that in the opinion of the Investigator could create a risk to the subject or could affect adherence with the trial protocol. * Subjects with inadequate haematological function (defined by leukocyte ≤ 2,0 x 10\^9 ; platelets ≤ 100 x 10\^9; haemoglobin ≤ 12 g/dl for female and ≤ 13 g/dl for male), liver function (defined by AST, ALT, alkaline phosphatase \> 2.0 times upper limit of normal), thyroid function (In particular subjects with clinically overt hyperthyroidism or clinically overt hypothyroidism and in any case according to physician's discretion). * Known hypersensitivity to gadolinium * Any other condition that would prevent the subject from undergoing an MRI scan (impairment of Kidney function, metal prosthesis etc.) * Immunosuppressive therapy 12 months before screening visit * Use of some recognized drugs involved as enzyme substrates, inducers or inhibitors in P450 system * Use of antiplatelet agents or antihyperlipidemics * Any contra-indication according to IFN beta 1a 44 mcg Summary of Product Characteristics (SmPC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12 | Month 12 | A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate at Month 12 and 24 | Month 12 and 24 | Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Annualized relapse rate was calculated by dividing the total number of relapse events by the total number of days subjects participated in the study. This number was then multiplied by 365.25 to get an annualized rate. |
| Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 3, 6, 12 and 24 | Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. |
| Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months | Baseline up to Month 24 | Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Percentage of subjects treated with glucocorticoids due to relapses during 24 Months were reported here. |
| Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 | Month 12 and 24 | Disability progression was assessed using EDSS. EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in multiple sclerosis (MS) . Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as an increase of EDSS score of at least 1.0 point compared to baseline for subjects with an EDSS =\< 4.0. For subjects with an EDSS= 0 at baseline, EDSS progression was defined as an increase of EDSS score of at least 1.5 point. Percentage of subjects free from EDSS progression at Month 12 and 24 were reported |
| Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression | Baseline to date at which the first confirmed EDSS progression occurs, assessed up to 24 months | EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. EDSS values obtained during clinical attacks are not excluded for the assessment of EDSS progression. However, EDSS values obtained during MS attacks that are not confirmed after two consecutive assessments will be excluded from statistical analysis of confirmed EDSS progression. Hazard ratio for time to first sustained EDSS progression was planned to be reported as per SAP. |
| Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24 | Month 24 | A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan. |
| Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 | Month 12 and 24 | CUA lesion was defined as new gadolinium (Gd)-enhancing lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting. |
| Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 | Month 12 and 24 | New Gd-enhancing Lesions are a measure of inflammatory activity and were assessed using the Magnetic Resonance Imaging (MRI) scan. |
| Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 | Month 12 and 24 | Mean number of new T1 (Hypointense) Lesions represents a measure of accumulation of inflammatory disease burden assessed on magnetic resonance imaging (MRI) scans. |
| Percentage of Relapse-Free Subjects at Month 12 and Month 24 | Month 12 and 24 | Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. |
| Number of Subjects With Premature Termination From Treatment | Baseline up to Month 24 | Number of subjects with premature termination from treatment were reported. |
| Median Change From Baseline in Whole Brain Volume at Month 12 and 24 | Baseline, Month 12 and 24 | Brain tissue volumes are inter-related and represent a measure of neurodegenerative aspects of the disease. |
| Hazard Ratio for Time to First Documented Relapse | Baseline up to Date at which first Relapse Occurs assessed up to 24 months | Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Hazard ratio for time to first documented relapse was planned to be reported as per SAP. |
| Median Change From Baseline in Regional Brain Volume at Month 12 and 24 | Baseline, Month 12 and 24 | Brain tissue volumes are inter-related and represent a measure of neurodegenerative aspects of the disease. |
| Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Screening, Baseline, Month 3, 6, 12 and 24 | Flu-like symptoms were measured using FLS score in which subjects were scored as per the presence and intensity of muscle aches, chills, and weakness, each separately, on a scale of 0-3 as follows: 0 = absent; 1 = mild, do not interfere with daily activities; 2 = moderate, sufficient to interfere with daily activities; and 3 = severe, bed rest require. Body temperature also was also recorded to determine the presence of fever using the following scale: 0 (≤ 37.2 °C); 1 (≥ 37.3 °C but \< 37.8 °C); 2 (≥ 37.8 but \< 38.4 °C); and 3 (≥ 38.4 °C).The scores for each symptom (muscle aches, chills, weakness, body temperature) was added together to provide the combined flu-like symptom score ranging from 0 to 12 where 0 indicates absence of any symptom and 12 indicates the worst severity of the symptoms. |
| Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Baseline up to Month 24 | AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 24 months. TEAEs include both Serious TEAEs and non-serious TEAEs. |
| Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters | From screening up to Month 24 | Laboratory assessment included haematology, chemistry, and urinalysis. Clinical significance was determined by the investigator. |
| Number of Subjects With One Concomitant Medication From Baseline up to Month 24 | Baseline up to Month 24 | Number of subjects with at least one concomitant medication from baseline up to month 24 were reported. |
| Time on Treatment (Adherence to Treatment) | Baseline up to 2.2 years | Time up to which subjects were adhered to the treatment was reported. |
| Cumulative Number of New T1 (Hypointense) Lesions | Baseline up to Month 24 | Cumulative number of new T1 (Hypointense) lesions were reported. |
Countries
Italy
Participant flow
Pre-assignment details
Subjects who had been receiving treatment with subcutaneous interferon (IFN) beta 1a 44 microgram (mcg) three times a week (TIW) for a minimum of 6 months and for not longer than 24 months before enrollment, were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) Subjects received 500 milligram (mg) curcumin orally twice a day along with IFN beta 1a 44 mcg subcutaneously TIW for approximately 24 months. | 40 |
| IFN Beta 1a 44 mcg TIW + Placebo Subjects received placebo matched to curcumin orally twice a day along with IFN beta 1a 44 mcg subcutaneously TIW for approximately 24 months. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Other | 6 | 7 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | IFN Beta 1a 44 mcg TIW + Placebo | Total |
|---|---|---|---|
| Age, Continuous | 36.5 years STANDARD_DEVIATION 8.6 | 34.3 years STANDARD_DEVIATION 9.4 | 35.4 years STANDARD_DEVIATION 9 |
| Sex: Female, Male Female | 28 Participants | 22 Participants | 50 Participants |
| Sex: Female, Male Male | 12 Participants | 18 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 38 | 16 / 40 |
| serious Total, serious adverse events | 1 / 38 | 0 / 40 |
Outcome results
Primary
Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12
A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan.
Time frame: Month 12
Population: ITT population included all randomized subjects.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12 | 4 Participants |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12 | 7 Participants |
p-value: 0.271Chi-squared
Secondary
Annualized Relapse Rate at Month 12 and 24
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Annualized relapse rate was calculated by dividing the total number of relapse events by the total number of days subjects participated in the study. This number was then multiplied by 365.25 to get an annualized rate.
Time frame: Month 12 and 24
Population: ITT population included all randomized subjects. Here, Number of subjects analyzed signifies those subjects who were evaluable for this outcome measure. Here Number analyzed signifies those subjects who were evaluable for this outcome measure at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Annualized Relapse Rate at Month 12 and 24 | Month 12 | 1.73 Relapse per year | Standard Deviation 0.7 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Annualized Relapse Rate at Month 12 and 24 | Month 24 | 1.05 Relapse per year | Standard Deviation 0.73 |
| IFN Beta 1a 44 mcg TIW + Placebo | Annualized Relapse Rate at Month 12 and 24 | Month 12 | 1.40 Relapse per year | Standard Deviation 0.65 |
| IFN Beta 1a 44 mcg TIW + Placebo | Annualized Relapse Rate at Month 12 and 24 | Month 24 | 1.14 Relapse per year | Standard Deviation 0.82 |
Secondary
Cumulative Number of New T1 (Hypointense) Lesions
Cumulative number of new T1 (Hypointense) lesions were reported.
Time frame: Baseline up to Month 24
Population: The Intent-to-Treat (ITT) population included all randomized subjects. Here Number of subjects analyzed included the subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Cumulative Number of New T1 (Hypointense) Lesions | 0.58 Lesions | Standard Deviation 1.32 |
| IFN Beta 1a 44 mcg TIW + Placebo | Cumulative Number of New T1 (Hypointense) Lesions | 0.39 Lesions | Standard Deviation 1.64 |
Secondary
Flu-like Symptoms (FLS) Assessed by FLS Scale Score
Flu-like symptoms were measured using FLS score in which subjects were scored as per the presence and intensity of muscle aches, chills, and weakness, each separately, on a scale of 0-3 as follows: 0 = absent; 1 = mild, do not interfere with daily activities; 2 = moderate, sufficient to interfere with daily activities; and 3 = severe, bed rest require. Body temperature also was also recorded to determine the presence of fever using the following scale: 0 (≤ 37.2 °C); 1 (≥ 37.3 °C but \< 37.8 °C); 2 (≥ 37.8 but \< 38.4 °C); and 3 (≥ 38.4 °C).The scores for each symptom (muscle aches, chills, weakness, body temperature) was added together to provide the combined flu-like symptom score ranging from 0 to 12 where 0 indicates absence of any symptom and 12 indicates the worst severity of the symptoms.
Time frame: Screening, Baseline, Month 3, 6, 12 and 24
Population: The Safety population included all subjects who received at least one administration of study medication. Here Number analyzed signifies those subjects who were evaluable for this outcome measure at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Screening | 2.39 Units on a scale | Standard Deviation 2.48 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Baseline | 2.22 Units on a scale | Standard Deviation 2.76 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 3 | 1.91 Units on a scale | Standard Deviation 1.89 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 6 | 1.96 Units on a scale | Standard Deviation 1.83 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 12 | 1.45 Units on a scale | Standard Deviation 1.68 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 24 | 1.68 Units on a scale | Standard Deviation 1.71 |
| IFN Beta 1a 44 mcg TIW + Placebo | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 12 | 1.36 Units on a scale | Standard Deviation 1.29 |
| IFN Beta 1a 44 mcg TIW + Placebo | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Screening | 2.43 Units on a scale | Standard Deviation 2.34 |
| IFN Beta 1a 44 mcg TIW + Placebo | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 6 | 1.91 Units on a scale | Standard Deviation 2.42 |
| IFN Beta 1a 44 mcg TIW + Placebo | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Baseline | 2.06 Units on a scale | Standard Deviation 2.21 |
| IFN Beta 1a 44 mcg TIW + Placebo | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 24 | 0.93 Units on a scale | Standard Deviation 0.92 |
| IFN Beta 1a 44 mcg TIW + Placebo | Flu-like Symptoms (FLS) Assessed by FLS Scale Score | Month 3 | 1.89 Units on a scale | Standard Deviation 1.74 |
Secondary
Hazard Ratio for Time to First Documented Relapse
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Hazard ratio for time to first documented relapse was planned to be reported as per SAP.
Time frame: Baseline up to Date at which first Relapse Occurs assessed up to 24 months
Population: ITT population included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Hazard Ratio for Time to First Documented Relapse | 0.808 Ratio |
Secondary
Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. EDSS values obtained during clinical attacks are not excluded for the assessment of EDSS progression. However, EDSS values obtained during MS attacks that are not confirmed after two consecutive assessments will be excluded from statistical analysis of confirmed EDSS progression. Hazard ratio for time to first sustained EDSS progression was planned to be reported as per SAP.
Time frame: Baseline to date at which the first confirmed EDSS progression occurs, assessed up to 24 months
Population: ITT population included all randomized subjects. Here, Number of subjects analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression | 0.309 Ratio |
Secondary
Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24
New Gd-enhancing Lesions are a measure of inflammatory activity and were assessed using the Magnetic Resonance Imaging (MRI) scan.
Time frame: Month 12 and 24
Population: The ITT population included all randomized subjects. Here Number analyzed signifies those subjects who were evaluable for this outcome measure at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 | Month 12 | 0.19 Lesions | Standard Deviation 0.79 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 | Month 24 | 0.21 Lesions | Standard Deviation 0.63 |
| IFN Beta 1a 44 mcg TIW + Placebo | Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 | Month 12 | 0.46 Lesions | Standard Deviation 1.61 |
| IFN Beta 1a 44 mcg TIW + Placebo | Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 | Month 24 | 0.13 Lesions | Standard Deviation 0.63 |
Secondary
Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24
Mean number of new T1 (Hypointense) Lesions represents a measure of accumulation of inflammatory disease burden assessed on magnetic resonance imaging (MRI) scans.
Time frame: Month 12 and 24
Population: The ITT population included all randomized subjects. Here Number analyzed signifies those subjects who were evaluable for this outcome measure at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 | Month 12 | 0.52 Lesions | Standard Deviation 1.28 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 | Month 24 | 0.19 Lesions | Standard Deviation 0.68 |
| IFN Beta 1a 44 mcg TIW + Placebo | Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 | Month 12 | 0.48 Lesions | Standard Deviation 1.87 |
| IFN Beta 1a 44 mcg TIW + Placebo | Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 | Month 24 | 0.04 Lesions | Standard Deviation 0.21 |
Secondary
Median Change From Baseline in Regional Brain Volume at Month 12 and 24
Brain tissue volumes are inter-related and represent a measure of neurodegenerative aspects of the disease.
Time frame: Baseline, Month 12 and 24
Population: As per change in Statistical Analysis Plan, data was not collected for this endpoint
Secondary
Median Change From Baseline in Whole Brain Volume at Month 12 and 24
Brain tissue volumes are inter-related and represent a measure of neurodegenerative aspects of the disease.
Time frame: Baseline, Month 12 and 24
Population: As per change in Statistical Analysis Plan, data was not collected for this endpoint
Secondary
Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters
Laboratory assessment included haematology, chemistry, and urinalysis. Clinical significance was determined by the investigator.
Time frame: From screening up to Month 24
Population: The Safety population included all subjects who received at least one administration of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters | 9 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters | 4 Subjects |
Secondary
Number of Subjects With One Concomitant Medication From Baseline up to Month 24
Number of subjects with at least one concomitant medication from baseline up to month 24 were reported.
Time frame: Baseline up to Month 24
Population: The ITT population included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With One Concomitant Medication From Baseline up to Month 24 | 28 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With One Concomitant Medication From Baseline up to Month 24 | 20 Subjects |
Secondary
Number of Subjects With Premature Termination From Treatment
Number of subjects with premature termination from treatment were reported.
Time frame: Baseline up to Month 24
Population: The Intent-to-Treat (ITT) population included all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Premature Termination From Treatment | Consent withdrawn | 2 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Premature Termination From Treatment | Protocol Violation | 2 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Premature Termination From Treatment | Lost to follow up | 0 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Premature Termination From Treatment | Unspecified | 6 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Premature Termination From Treatment | Adverse event | 1 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Premature Termination From Treatment | Unspecified | 7 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Premature Termination From Treatment | Adverse event | 3 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Premature Termination From Treatment | Consent withdrawn | 1 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Premature Termination From Treatment | Lost to follow up | 2 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Premature Termination From Treatment | Protocol Violation | 3 Subjects |
Secondary
Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation
AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 24 months. TEAEs include both Serious TEAEs and non-serious TEAEs.
Time frame: Baseline up to Month 24
Population: The Safety population included all subjects who received at least one administration of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TEAE | 16 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TE-SAE | 1 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TEAEs leading to discontinuation | 1 Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TEAEs leading to death | 0 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TEAEs leading to death | 0 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TEAE | 16 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TEAEs leading to discontinuation | 3 Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation | Subjects with TE-SAE | 0 Subjects |
Secondary
Percentage of Relapse-Free Subjects at Month 12 and Month 24
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Time frame: Month 12 and 24
Population: ITT population included all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Relapse-Free Subjects at Month 12 and Month 24 | Month 12 | 75.0 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Relapse-Free Subjects at Month 12 and Month 24 | Month 24 | 60.0 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Relapse-Free Subjects at Month 12 and Month 24 | Month 12 | 67.5 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Relapse-Free Subjects at Month 12 and Month 24 | Month 24 | 50.0 Percentage of subjects |
Secondary
Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24
Disability progression was assessed using EDSS. EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in multiple sclerosis (MS) . Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as an increase of EDSS score of at least 1.0 point compared to baseline for subjects with an EDSS =\< 4.0. For subjects with an EDSS= 0 at baseline, EDSS progression was defined as an increase of EDSS score of at least 1.5 point. Percentage of subjects free from EDSS progression at Month 12 and 24 were reported
Time frame: Month 12 and 24
Population: ITT population included all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 | Month 12 | 92.5 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 | Month 24 | 90.0 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 | Month 12 | 82.5 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 | Month 24 | 85.0 Percentage of subjects |
Secondary
Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Percentage of subjects treated with glucocorticoids due to relapses during 24 Months were reported here.
Time frame: Baseline up to Month 24
Population: ITT population included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months | 30.0 Percentage of Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months | 35.0 Percentage of Subjects |
Secondary
Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24
A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan.
Time frame: Month 24
Population: ITT population included all randomized subjects.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24 | 20.0 Percentage of subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24 | 17.5 Percentage of subjects |
Secondary
Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24
CUA lesion was defined as new gadolinium (Gd)-enhancing lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting.
Time frame: Month 12 and 24
Population: ITT population included all randomized subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 | Month 12 | 7.5 Percentage of Subjects |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 | Month 24 | 15.0 Percentage of Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 | Month 12 | 17.5 Percentage of Subjects |
| IFN Beta 1a 44 mcg TIW + Placebo | Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 | Month 24 | 12.5 Percentage of Subjects |
Secondary
Time on Treatment (Adherence to Treatment)
Time up to which subjects were adhered to the treatment was reported.
Time frame: Baseline up to 2.2 years
Population: The Safety population included all subjects who received at least one administration of study medication.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Time on Treatment (Adherence to Treatment) | 1.93 Years | Full Range 0.49 |
| IFN Beta 1a 44 mcg TIW + Placebo | Time on Treatment (Adherence to Treatment) | 1.92 Years | Full Range 0.6 |
Secondary
Total Number of Reported Relapses at Month 3, 6, 12 and 24
Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Time frame: Month 3, 6, 12 and 24
Population: The ITT population included all randomized subjects. Here, Number of subjects analyzed signifies those subjects who were evaluable for this outcome measure. Here Number analyzed signifies those subjects who were evaluable for this outcome measure at the specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 3 | 1.00 Relapses | Standard Deviation 0 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 6 | 1.00 Relapses | Standard Deviation 0 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 12 | 1.50 Relapses | Standard Deviation 0.58 |
| IFN Beta 1a 44 mcg TIW + Curcumin (BCM95) | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 24 | 1.57 Relapses | Standard Deviation 0.79 |
| IFN Beta 1a 44 mcg TIW + Placebo | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 24 | 1.75 Relapses | Standard Deviation 0.96 |
| IFN Beta 1a 44 mcg TIW + Placebo | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 3 | 1.00 Relapses | Standard Deviation 0 |
| IFN Beta 1a 44 mcg TIW + Placebo | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 12 | 1.00 Relapses | Standard Deviation 0 |
| IFN Beta 1a 44 mcg TIW + Placebo | Total Number of Reported Relapses at Month 3, 6, 12 and 24 | Month 6 | 1.00 Relapses | — |