Relapsing-remitting Multiple Sclerosis, RRMS
Conditions
Keywords
relapsing-remitting multiple sclerosis, RRMS
Brief summary
A randomized, multi-center, double-blind, proof-of-concept study to assess the effect of multiple infusions of AIN457 (10 mg/kg) versus placebo on disease activity as measured by MRI scans over a 24 week period in patients with relapsing-remitting multiple sclerosis
Interventions
DRUGAIN457
infusion 10 mg/Kg
DRUGPlacebo
infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
\-
Exclusion criteria
\-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | weeks 4,8,12,16,20,24,28 | Combined unique active lesions (CUAL) observed on brain MRI scans performed every 4th week from week 4 to week 24 in patients with relapsing-remitting multiple sclerosis (RRMS). CUAL is defined as: new gadolinium (Gd)-enhancing lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Raw Number of Cumulative New Gd-T1 Lesions | MRI brain scans performed every 4 weeks at week 4, 8, 12, 16, 20, 24 and 28 (EOS). | The summary of raw number of cumulative new Gadolinium-enhanced T1 lesions observed on brain MRI scans performed every 4th week from WK 4 to WK 28. The end-point is week 24. |
| Raw Number of Cumulative New Gd-T2 Lesions | MRI brain scans performed every 4 weeks at week 4, 8, 12, 16, 20, 24 and 28 (EOS). | The summary of raw number of cumulative new Gadolinium-enhanced T2 lesions observed on brain MRI scans performed every 4th week from WK 4 to WK 28. The endpoint is week 24. |
Countries
Czechia, Russia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AIN457 IV dose 10 mg/kg week 0, 2, 4, 8, 12, 16, and 20. | 38 |
| Placebo Placebo IV week 0, 2, 4, 8, 12, 16, and 20. | 35 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Test Proceedure reults | 0 | 1 |
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo | Total | AIN457 |
|---|---|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 9.9 | 34.5 years STANDARD_DEVIATION 9.95 | 36.1 years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 69 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) White | 33 Participants | 69 Participants | 36 Participants |
| Sex: Female, Male Female | 29 Participants | 50 Participants | 21 Participants |
| Sex: Female, Male Male | 6 Participants | 23 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 35 | 13 / 38 |
| serious Total, serious adverse events | 0 / 35 | 0 / 38 |
Outcome results
Primary
Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment
Combined unique active lesions (CUAL) observed on brain MRI scans performed every 4th week from week 4 to week 24 in patients with relapsing-remitting multiple sclerosis (RRMS). CUAL is 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: weeks 4,8,12,16,20,24,28
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 12 (n=35,31) | 5.4 Combined Unique Active Lesions |
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 20 (n=34,27) | 7.7 Combined Unique Active Lesions |
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 16 (n=32,29) | 6.0 Combined Unique Active Lesions |
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 24 (n=32,24) | 7.7 Combined Unique Active Lesions |
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 8 (n=36, 31) | 3.9 Combined Unique Active Lesions |
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 28 (n=32,29) | 9.4 Combined Unique Active Lesions |
| AIN457B | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 4 (n=37,34) | 2.4 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 28 (n=32,29) | 19.9 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 16 (n=32,29) | 11.5 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 4 (n=37,34) | 3.2 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 8 (n=36, 31) | 5.4 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 20 (n=34,27) | 13.0 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 24 (n=32,24) | 15.1 Combined Unique Active Lesions |
| Placebo | Summary of Raw Number of Cumulative Combined Unique Active Lesions in Patients With Relapsing Remitting Multiple Sclerosis by Visit and Treatment | Week 12 (n=35,31) | 8.6 Combined Unique Active Lesions |
Secondary
Raw Number of Cumulative New Gd-T1 Lesions
The summary of raw number of cumulative new Gadolinium-enhanced T1 lesions observed on brain MRI scans performed every 4th week from WK 4 to WK 28. The end-point is week 24.
Time frame: MRI brain scans performed every 4 weeks at week 4, 8, 12, 16, 20, 24 and 28 (EOS).
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 24 (n=32,24) | 5.4 cumulative new Gd-T1 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 28 (n=32,29) | 6.5 cumulative new Gd-T1 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 4 (n=37,34) | 1.4 cumulative new Gd-T1 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 8 (n= 36,31) | 2.6 cumulative new Gd-T1 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 12 (n=35,31) | 4.3 cumulative new Gd-T1 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 16 (n= 32,29) | 4.0 cumulative new Gd-T1 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T1 Lesions | Week 20 (n=34,27) | 5.6 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 12 (n=35,31) | 5.5 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 20 (n=34,27) | 9.2 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 24 (n=32,24) | 11.1 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 8 (n= 36,31) | 3.0 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 28 (n=32,29) | 14.4 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 16 (n= 32,29) | 7.8 cumulative new Gd-T1 lesions |
| Placebo | Raw Number of Cumulative New Gd-T1 Lesions | Week 4 (n=37,34) | 1.7 cumulative new Gd-T1 lesions |
Secondary
Raw Number of Cumulative New Gd-T2 Lesions
The summary of raw number of cumulative new Gadolinium-enhanced T2 lesions observed on brain MRI scans performed every 4th week from WK 4 to WK 28. The endpoint is week 24.
Time frame: MRI brain scans performed every 4 weeks at week 4, 8, 12, 16, 20, 24 and 28 (EOS).
Population: full analysis Set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 8 (n=36,31) | 3.6 Cumulative new Gd-T2 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 20 (n= 34,27) | 7.2 Cumulative new Gd-T2 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 12 (n=35,31) | 5.0 Cumulative new Gd-T2 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 4 (n= 37,34) | 2.3 Cumulative new Gd-T2 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 16 (n=32,29) | 5.6 Cumulative new Gd-T2 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 28 (n=32,29) | 8.8 Cumulative new Gd-T2 lesions |
| AIN457B | Raw Number of Cumulative New Gd-T2 Lesions | Week 24 (n=32,24) | 7.2 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 28 (n=32,29) | 19.1 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 20 (n= 34,27) | 12.3 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 24 (n=32,24) | 14.6 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 4 (n= 37,34) | 3.1 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 8 (n=36,31) | 5.4 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 12 (n=35,31) | 8.3 Cumulative new Gd-T2 lesions |
| Placebo | Raw Number of Cumulative New Gd-T2 Lesions | Week 16 (n=32,29) | 11.0 Cumulative new Gd-T2 lesions |