Relapsing Multiple Sclerosis
Conditions
Keywords
Relapsing Multiple Sclerosis, Atacicept
Brief summary
To evaluate the safety and tolerability of atacicept and to explore if atacicept reduces central nervous system inflammation in subjects with relapsing multiple sclerosis (RMS) as assessed by frequent magnetic resonance imaging (MRI). This study is randomised. Study medication is administered via subcutaneous (under the skin) injections.
Interventions
DRUGAtacicept
Atacicept will be administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks.
Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks.
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
\- Diagnosis of RMS (as per McDonald criteria, 2005) Other protocol-defined inclusion criteria could apply.
Exclusion criteria
* Have primary progressive multiple sclerosis (MS) * Have secondary progressive MS without superimposed relapses * Relevant cardiac, hepatic and renal diseases as specified in the protocol * Pretreatment with immunosuppressants and immunomodulating drugs as specified in the protocol * Clinical significant abnormalities in blood cell counts and immunoglobulin levels as specified in the protocol * Clinical significant acute or chronic infections as specified in the protocol Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan | Weeks 12 to 36 | Analysis of T1 Gd-enhancing lesions was done using magnetic resonance imaging (MRI) scans. Only post-baseline scans were included in the calculation of this endpoint (excluding the Study Day 1 scan which had been conducted before first dosing). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of New T1 Gd-enhancing Lesions Per Participant | Weeks 12, 24, 36 | Analysis of new T1 Gd-enhancing lesions was done using MRI scans. |
| Percentage of Participants Free From Relapses | Baseline up to Week 36 | A relapse was defined as the fulfillment of all the following criteria: a) neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours; b) absence of fever or known infection (fever with temperature \[axillary, orally, or intrauriculary\] greater than (\>) 37.5 degrees Celsius or 99.5 degrees Fahrenheit); and c) objective neurological impairment, correlating with the participant's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. Percentage of participants free from relapses during 36-week treatment period was reported. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | From the first dose of study drug administration up to 12 weeks after the last dose of the study drug | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE 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. Treatment-emergent are events between first dose of study drug up to 12 weeks after the last dose of the study drug that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAEs included subjects with both non serious and serious TEAEs. |
Countries
Australia, Austria, Belgium, Canada, Czechia, France, Germany, Lebanon, Lithuania, Netherlands, Russia, Spain, Sweden, Switzerland, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 32 weeks. | 63 |
| Atacicept 25 mg Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 32 weeks. | 63 |
| Atacicept 75 mg Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 32 weeks. | 64 |
| Atacicept 150 mg Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 32 weeks. | 65 |
| Total | 255 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 3 | 1 |
| Overall Study | Death | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 3 | 3 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 |
| Overall Study | Other | 1 | 5 | 1 | 4 |
| Overall Study | Premature termination of clinical trial | 37 | 32 | 35 | 35 |
| Overall Study | Randomized, but not treated | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Atacicept 25 mg | Atacicept 75 mg | Atacicept 150 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 37.7 years STANDARD_DEVIATION 10.5 | 37.5 years STANDARD_DEVIATION 8.5 | 38.0 years STANDARD_DEVIATION 10.1 | 37.5 years STANDARD_DEVIATION 10.5 | 37.7 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 45 Participants | 34 Participants | 44 Participants | 46 Participants | 169 Participants |
| Sex: Female, Male Male | 18 Participants | 29 Participants | 20 Participants | 19 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 63 | 30 / 63 | 34 / 63 | 44 / 65 |
| serious Total, serious adverse events | 1 / 63 | 3 / 63 | 3 / 63 | 1 / 65 |
Outcome results
Primary
Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan
Analysis of T1 Gd-enhancing lesions was done using magnetic resonance imaging (MRI) scans. Only post-baseline scans were included in the calculation of this endpoint (excluding the Study Day 1 scan which had been conducted before first dosing).
Time frame: Weeks 12 to 36
Population: ITT population included all randomized participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan | 3.07 lesions/participant/scan |
| Atacicept 25 mg | Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan | 2.26 lesions/participant/scan |
| Atacicept 75 mg | Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan | 2.30 lesions/participant/scan |
| Atacicept 150 mg | Mean Number of Time Constant 1 (T1) Gadolinium (Gd)-Enhancing Lesions Per Participant Per Scan | 2.49 lesions/participant/scan |
Secondary
Number of New T1 Gd-enhancing Lesions Per Participant
Analysis of new T1 Gd-enhancing lesions was done using MRI scans.
Time frame: Weeks 12, 24, 36
Population: ITT population included all randomized participants. 'n' signifies participants who were evaluable for this measure at given time points for each group, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Number of New T1 Gd-enhancing Lesions Per Participant | Week 12 (n=55, 45, 50, 55) | 2.55 lesions/participant | Standard Deviation 7.95 |
| Placebo | Number of New T1 Gd-enhancing Lesions Per Participant | Week 36 (n=23, 22, 24, 26) | 0.43 lesions/participant | Standard Deviation 0.9 |
| Placebo | Number of New T1 Gd-enhancing Lesions Per Participant | Week 24 (n=41, 34, 37, 41) | 0.83 lesions/participant | Standard Deviation 1.7 |
| Atacicept 25 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 12 (n=55, 45, 50, 55) | 2.71 lesions/participant | Standard Deviation 7.67 |
| Atacicept 25 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 36 (n=23, 22, 24, 26) | 1.68 lesions/participant | Standard Deviation 5.09 |
| Atacicept 25 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 24 (n=41, 34, 37, 41) | 1.50 lesions/participant | Standard Deviation 2.79 |
| Atacicept 75 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 24 (n=41, 34, 37, 41) | 1.54 lesions/participant | Standard Deviation 2.96 |
| Atacicept 75 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 12 (n=55, 45, 50, 55) | 3.20 lesions/participant | Standard Deviation 6.41 |
| Atacicept 75 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 36 (n=23, 22, 24, 26) | 1.38 lesions/participant | Standard Deviation 1.93 |
| Atacicept 150 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 12 (n=55, 45, 50, 55) | 2.96 lesions/participant | Standard Deviation 6.58 |
| Atacicept 150 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 36 (n=23, 22, 24, 26) | 0.54 lesions/participant | Standard Deviation 1.07 |
| Atacicept 150 mg | Number of New T1 Gd-enhancing Lesions Per Participant | Week 24 (n=41, 34, 37, 41) | 1.54 lesions/participant | Standard Deviation 2.94 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE 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. Treatment-emergent are events between first dose of study drug up to 12 weeks after the last dose of the study drug that were absent before treatment or that worsened relative to pretreatment state. Number of subjects with TEAEs included subjects with both non serious and serious TEAEs.
Time frame: From the first dose of study drug administration up to 12 weeks after the last dose of the study drug
Population: Safety population included all participants who received at least 1 dose of treatment (either active or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 46 participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 1 participants |
| Atacicept 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 3 participants |
| Atacicept 25 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 40 participants |
| Atacicept 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 39 participants |
| Atacicept 75 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 3 participants |
| Atacicept 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 52 participants |
| Atacicept 150 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 1 participants |
Secondary
Percentage of Participants Free From Relapses
A relapse was defined as the fulfillment of all the following criteria: a) neurological abnormality, either newly appearing or re-appearing, with abnormality specified by both i) neurological abnormality separated by at least 30 days from onset of a preceding clinical event, and ii) neurological abnormality lasting for at least 24 hours; b) absence of fever or known infection (fever with temperature \[axillary, orally, or intrauriculary\] greater than (\>) 37.5 degrees Celsius or 99.5 degrees Fahrenheit); and c) objective neurological impairment, correlating with the participant's reported symptoms, defined as either i) increase in at least 1 of the functional systems of the Expanded Disability Status Scale (EDSS), or ii) increase of the total EDSS score. Percentage of participants free from relapses during 36-week treatment period was reported.
Time frame: Baseline up to Week 36
Population: ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Free From Relapses | 81.0 percentage of participants |
| Atacicept 25 mg | Percentage of Participants Free From Relapses | 69.8 percentage of participants |
| Atacicept 75 mg | Percentage of Participants Free From Relapses | 71.9 percentage of participants |
| Atacicept 150 mg | Percentage of Participants Free From Relapses | 61.5 percentage of participants |