Multiple Sclerosis
Conditions
Brief summary
Multiple sclerosis (MS) is a chronic inflammatory disease associated with central nervous system (CNS) demyelination and subsequent axonal degeneration. Multiple sclerosis exhibits an unpredictable and variable clinical course. Multiple sclerosis plaques contain numerous types of cells and infiltrating macrophages have been identified to contribute significantly to demyelination in both clinical MS and animal models of MS. Granulocyte-macrophage colony-stimulating factor (GM CSF) stimulates proliferation and activation of macrophages, monocytes, neutrophils, eosinophils, dendritic cells and microglia with subsequent induction of proinflammatory biomolecules. Therefore blocking GM CSF activity might be a therapeutic approach for the treatment of MS.
Detailed description
Recent clinical studies demonstrated a possible dysregulation of the balance of pro and anti inflammatory lymphocytes, which may contribute to the pathogenesis of MS. It was shown in animal models of EAE that during the disease effect or phase GM CSF sustained neuroinflammation via myeloid cells that infiltrate the CNS proving an essential role of GM CSF in encephalitogenicity.
Interventions
BIOLOGICALMOR103
Anti-GM-CSF monoclonal antibody
OTHERPlacebo
Placebo to anti-GM-CSF monoclonal antibody
Sponsors
MorphoSys AG
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
Key Inclusion Criteria: Outpatients with a diagnosis of RRMS or SPMS, who are currently not being treated and who have at least 1 of the following: * At least 1 documented relapse within 1 year before Screening, or * Two documented relapses within the past 2 years before Screening, or * A new gadolinium (Gd)-enhancing lesion on magnetic resonance imaging (MRI) T1-weighted imaging within 1 year before Screening, or * A new T2 lesion on MRI within 1 year before Screening. The patient must have 10 or less, Gd-enhancing lesions per T1-weighted MRI at Screening as assessed by a central reader. The patient must be able and willing to ambulate, with an Expanded Disability Status Scale (EDSS) score of ≥ 2.0 and ≤ 6.5 at both the Screening Visit and the Baseline Visit Key
Exclusion criteria
1. A patient with primary progressive MS (PPMS) 2. A patient who has previously received at any time any of the following * B-cell or T-cell depleting therapies * Cytotoxic agents, any immunosuppressive/immunomodulating agents 3. A patient who has not stabilized, in the opinion of the investigator 4. A patient with any medical condition or uncontrolled disease states other than MS requiring or likely to require systemic treatment with corticosteroids or other immune compromising agents 5. A patient with current or a history of major chronic inflammatory autoimmune diseases other than MS 6. A patient with any type of infection 7. Patients on chronic prophylactic or suppressive antibiotic, antifungal,or antiviral agents 8. A patient with a history of tuberculosis. 9. A patient with any signs of excretory hepatic or kidney dysfunction 10. A patient with a positive test for Hepatitis B or Hepatitis C
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | From the first dose (week 0) to study endpoint (week 20) | The safety of multiple doses of MOR103 in patients with relapsing-remitting or secondary progressive multiple sclerosis (MS) was assessed by evaluation of the incidence of TEAEs and TESAEs. A full listing of adverse events recorded during this trial can be found in the Adverse Events section. AEs were regarded as treatment emergent if they started on or after the first date of study drug administration or if they were present prior to the first date of study drug administration and increased in severity or relationship to study drug during the study. AEs were coded using MedDRA version 16.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Serum Concentration of MOR103 Over Time | Week 0 (dose 1) to week 20 (end of study) | MOR103 serum levels were measured at each visit. At all visits during the dosing period (weeks 0, 2, 6, 8, and 10), serum samples were taken before MOR103 administration (pre-dose) and 1 hour after the dose. In addition, at week 0 (first dose) and week 10 (last dose), additional samples were obtained at 2 hours and 4 hours after MOR103 administration. At visits that followed the dosing period (weeks 12, 14, 16, and 20), a single serum sample was obtained at any time during the visit. |
| Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 0 (first dose) and week 10 (last dose) | At the week 0 (first dose) and week 10 (last dose) visits, serum samples were obtained at pre-dose and at 1, 2, and 4 hours after the dose. Cmax values for each patient were calculated based on these data, and the mean Cmax values for the dose cohort are presented here. Because Cmax refers to the maximum serum concentration, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable, as they represent the concentration of MOR103, but not the Cmax. |
| Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 0 (first dose) and week 10 (last dose) | At the week 0 (first dose) and week 10 (last dose) visits, serum samples were obtained at pre-dose and at 1, 2, and 4 hours after the dose. Tmax values for each patient were calculated based on these data, and the mean Tmax values for the dose cohort are presented here. Because Tmax refers to the time to maximum serum concentration, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable. |
| Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Baseline, week 14, week 16, and week 20/end of study | To assess the potential immunogenicity of MOR103, a central bioanalytical laboratory (Eurofins Medinet BV, Breda, The Netherlands) tested serum samples obtained at baseline and at 3 post-treatment time points (week 14, week 16, and week 20/end of study) for anti-MOR103 antibodies. |
| Number of New T1 Gadolinium-enhancing Lesions | Week 4, week 8, week 12, and week 16. | Magnetic resonance imaging (MRI) tests were performed at screening (to confirm subject eligibility) and at Weeks 4, 8, 2, and 16. MRIs at post-screening time points were used to assess the number of new lesions as revealed by gadolinium (Gd) enhancement. Gd-enhanced MRIs reveal new brain lesions reflecting areas of active inflammation. MRI images were assessed centrally by Synarc A/S (Hamburg, Germany). |
| Number of New or Enlarging T2 Lesions | Week 8, week 12, and week 16. | T2-weighted magnetic resonance imaging (MRI) tests were performed at Weeks 8, 12, and 16 to assess the number of new or enlarging T2 brain lesions, a sign of MS activity. MRI images were assessed centrally by Synarc A/S (Hamburg, Germany). |
| Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC | Week 0 (first dose) and week 10 (last dose) | At week 0 (first dose) and week 10 (last dose), serum samples were obtained at pre-dose and at 1, 2, 4, and 336 hours after start of dosing. To calculate the accumulation ratio, the apparent AUC calculated for the last dose was divided by the apparent AUC following the first dose using the described time points for each dosing. Because AUC is a summary outcome, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable. |
Countries
Germany, Poland, United Kingdom
Participant flow
Recruitment details
Subjects were recruited and screened between 2 January 2012 and 22 July 2013 at 5 trial centers in Europe (1 in Germany, 2 in Poland, and 2 in the United Kingdom). Screening could occur between 10 and 35 days prior to dosing on day 1. Subject eligibility was determined at the screening visit and confirmed before the first dose on day 1.
Participants by arm
| Arm | Count |
|---|---|
| MOR103 0.5 mg/kg MOR103 0.5 mg/kg administered intravenously every 2 weeks for a total of 6 doses. | 8 |
| MOR103 1.0 mg/kg MOR103 1.0 mg/kg administered intravenously every 2 weeks for a total of 6 doses. | 8 |
| MOR103 2.0 mg/kg MOR103 2.0 mg/kg administered intravenously every 2 weeks for a total of 6 doses. | 9 |
| Pooled Placebo Placebo administered intravenously once every 2 weeks for a total of 6 doses | 6 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Consent withdrawn | 0 | 1 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | MOR103 1.0 mg/kg | Total | Pooled Placebo | MOR103 0.5 mg/kg | MOR103 2.0 mg/kg |
|---|---|---|---|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 4.98 | 47.3 years STANDARD_DEVIATION 10.42 | 43.5 years STANDARD_DEVIATION 15.03 | 47.8 years STANDARD_DEVIATION 10.63 | 48.3 years STANDARD_DEVIATION 11.47 |
| Diagnosis Relapsing-remitting multiple sclerosis | 6 participants | 25 participants | 6 participants | 7 participants | 6 participants |
| Diagnosis Secondary progressive multiple sclerosis | 1 participants | 5 participants | 0 participants | 1 participants | 3 participants |
| Diagnosis Unknown | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Gadolinium (Gd)-enhancing lesions 1 or more Gd-enhancing lesions | 3 participants | 10 participants | 3 participants | 3 participants | 1 participants |
| Gadolinium (Gd)-enhancing lesions No Gd-enhancing lesions | 5 participants | 21 participants | 3 participants | 5 participants | 8 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 29 Participants | 5 Participants | 7 Participants | 9 Participants |
| Region of Enrollment Germany | 5 participants | 12 participants | 2 participants | 2 participants | 3 participants |
| Region of Enrollment Poland | 1 participants | 6 participants | 2 participants | 2 participants | 1 participants |
| Region of Enrollment United Kingdom | 2 participants | 13 participants | 2 participants | 4 participants | 5 participants |
| Sex: Female, Male Female | 6 Participants | 20 Participants | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 11 Participants | 3 Participants | 4 Participants | 2 Participants |
| Time since diagnosis | 13.1 years STANDARD_DEVIATION 7.38 | 9.0 years STANDARD_DEVIATION 8.51 | 5.5 years STANDARD_DEVIATION 7.66 | 5.6 years STANDARD_DEVIATION 8.68 | 10.7 years STANDARD_DEVIATION 8.97 |
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 | 8 / 8 | 8 / 8 | 8 / 9 | 6 / 6 |
| serious Total, serious adverse events | 0 / 8 | 1 / 8 | 0 / 9 | 1 / 6 |
Outcome results
Primary
Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)
The safety of multiple doses of MOR103 in patients with relapsing-remitting or secondary progressive multiple sclerosis (MS) was assessed by evaluation of the incidence of TEAEs and TESAEs. A full listing of adverse events recorded during this trial can be found in the Adverse Events section. AEs were regarded as treatment emergent if they started on or after the first date of study drug administration or if they were present prior to the first date of study drug administration and increased in severity or relationship to study drug during the study. AEs were coded using MedDRA version 16.1
Time frame: From the first dose (week 0) to study endpoint (week 20)
Population: All subjects who received 1 or more dose of placebo or MOR103 (safety population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MOR103 0.5 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 100 percentage of participants |
| MOR103 0.5 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE related to treatment | 75.0 percentage of participants |
| MOR103 0.5 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE with MS exacerbation/relapse | 62.5 percentage of participants |
| MOR103 0.5 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 0 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE related to treatment | 50.0 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE with MS exacerbation/relapse | 12.5 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 12.5 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 100 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE with MS exacerbation/relapse | 0.0 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE related to treatment | 33.3 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 0 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 88.9 percentage of participants |
| Pooled Placebo | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAE | 16.7 percentage of participants |
| Pooled Placebo | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE related to treatment | 83.3 percentage of participants |
| Pooled Placebo | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE | 100 percentage of participants |
| Pooled Placebo | Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAE with MS exacerbation/relapse | 50.0 percentage of participants |
Secondary
Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC
At week 0 (first dose) and week 10 (last dose), serum samples were obtained at pre-dose and at 1, 2, 4, and 336 hours after start of dosing. To calculate the accumulation ratio, the apparent AUC calculated for the last dose was divided by the apparent AUC following the first dose using the described time points for each dosing. Because AUC is a summary outcome, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable.
Time frame: Week 0 (first dose) and week 10 (last dose)
Population: Pharmocokinetic (PK) analyses were conducted on the PK set, which included all MOR103-treated patients except for 2 patients who discontinued after 2 doses of trial medication (one each in the 1.0 and 2.0 mg/kg groups). Data were missing for one patient in the MOR103 2.0 mg/kg group (n = 7).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOR103 0.5 mg/kg | Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC | 1.20 ratio of AUC values | Standard Deviation 0.13 |
| MOR103 1.0 mg/kg | Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC | 1.31 ratio of AUC values | Standard Deviation 0.2 |
| MOR103 2.0 mg/kg | Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC | 1.32 ratio of AUC values | Standard Deviation 0.22 |
Secondary
Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses
At the week 0 (first dose) and week 10 (last dose) visits, serum samples were obtained at pre-dose and at 1, 2, and 4 hours after the dose. Cmax values for each patient were calculated based on these data, and the mean Cmax values for the dose cohort are presented here. Because Cmax refers to the maximum serum concentration, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable, as they represent the concentration of MOR103, but not the Cmax.
Time frame: Week 0 (first dose) and week 10 (last dose)
Population: Pharmocokinetic (PK) analyses were conducted on the PK set, which included all MOR103-treated patients except for 2 patients who discontinued after 2 doses of trial medication (one each in the 1.0 and 2.0 mg/kg groups). PK data for the last dose were missing for one patient in the MOR103 2.0 mg/kg group (n = 7).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOR103 0.5 mg/kg | Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 0 (first dose) | 8.60 mg/L | Standard Deviation 2.08 |
| MOR103 0.5 mg/kg | Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 10 (last dose) | 9.03 mg/L | Standard Deviation 1.81 |
| MOR103 1.0 mg/kg | Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 0 (first dose) | 18.70 mg/L | Standard Deviation 2.97 |
| MOR103 1.0 mg/kg | Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 10 (last dose) | 22.53 mg/L | Standard Deviation 7.71 |
| MOR103 2.0 mg/kg | Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 0 (first dose) | 35.67 mg/L | Standard Deviation 6.73 |
| MOR103 2.0 mg/kg | Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses | Week 10 (last dose) | 40.37 mg/L | Standard Deviation 6.37 |
Secondary
Mean Serum Concentration of MOR103 Over Time
MOR103 serum levels were measured at each visit. At all visits during the dosing period (weeks 0, 2, 6, 8, and 10), serum samples were taken before MOR103 administration (pre-dose) and 1 hour after the dose. In addition, at week 0 (first dose) and week 10 (last dose), additional samples were obtained at 2 hours and 4 hours after MOR103 administration. At visits that followed the dosing period (weeks 12, 14, 16, and 20), a single serum sample was obtained at any time during the visit.
Time frame: Week 0 (dose 1) to week 20 (end of study)
Population: Pharmacokinetic (PK) analyses were conducted on the PK set, which included all MOR103-treated patients except for 2 patients who discontinued after 2 doses of trial medication (one each in the 1.0 and 2.0 mg/kg groups). PK data were not available for all patients at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 2 hours after 6th and last dose | 8.820 mg/L | Standard Deviation 2.037 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 4: 1 hour after 3rd dose | 6.972 mg/L | Standard Deviation 2.947 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: Pre-dose | 0 mg/L | Standard Deviation 0 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 1 hour after 6th and last dose | 8.536 mg/L | Standard Deviation 1.787 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 6: Pre-dose | 0.924 mg/L | Standard Deviation 0.322 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 4 hours after 1st dose | 7.458 mg/L | Standard Deviation 1.337 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: Pre-dose | 0.929 mg/L | Standard Deviation 0.323 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 6: 1 hour after 4th dose | 9.298 mg/L | Standard Deviation 1.155 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 20 | 0.118 mg/L | Standard Deviation 0.076 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 8: 1 hour after 5th dose | 9.120 mg/L | Standard Deviation 1.618 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 8: Pre-dose | 0.934 mg/L | Standard Deviation 0.386 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 14 | 0.351 mg/L | Standard Deviation 0.14 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 2: Pre-dose | 0.555 mg/L | Standard Deviation 0.225 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 16 | 0.175 mg/L | Standard Deviation 0.072 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 12 | 0.907 mg/L | Standard Deviation 0.24 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 2: 1 hour after 2nd dose | 8.053 mg/L | Standard Deviation 0.839 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 2 hours after 1st dose | 7.935 mg/L | Standard Deviation 1.827 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 4 hours after 6th and last dose | 7.942 mg/L | Standard Deviation 1.105 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 4: Pre-dose | 1.671 mg/L | Standard Deviation 2.547 |
| MOR103 0.5 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 1 hour after 1st dose | 7.686 mg/L | Standard Deviation 3 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 14 | 0.869 mg/L | Standard Deviation 0.341 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: Pre-dose | 3.778 mg/L | Standard Deviation 9.995 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 1 hour after 1st dose | 17.907 mg/L | Standard Deviation 3.18 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 2 hours after 1st dose | 17.715 mg/L | Standard Deviation 3.004 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 4 hours after 1st dose | 16.765 mg/L | Standard Deviation 2.816 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 2: Pre-dose | 1.422 mg/L | Standard Deviation 0.588 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 2: 1 hour after 2nd dose | 22.021 mg/L | Standard Deviation 6.7 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 4: Pre-dose | 1.544 mg/L | Standard Deviation 0.283 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 4: 1 hour after 3rd dose | 21.351 mg/L | Standard Deviation 5.435 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 6: Pre-dose | 1.831 mg/L | Standard Deviation 0.297 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 6: 1 hour after 4th dose | 21.836 mg/L | Standard Deviation 6.077 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 8: Pre-dose | 2.138 mg/L | Standard Deviation 0.867 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 8: 1 hour after 5th dose | 22.283 mg/L | Standard Deviation 4.738 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: Pre-dose | 2.143 mg/L | Standard Deviation 0.884 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 1 hour after 6th and last dose | 23.675 mg/L | Standard Deviation 7.695 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 2 hours after 6th and last dose | 21.204 mg/L | Standard Deviation 6.972 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 4 hours after 6th and last dose | 20.960 mg/L | Standard Deviation 6.521 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 12 | 2.065 mg/L | Standard Deviation 0.606 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 16 | 0.416 mg/L | Standard Deviation 0.205 |
| MOR103 1.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 20 | 0.179 mg/L | Standard Deviation 0.097 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 1 hour after 1st dose | 34.834 mg/L | Standard Deviation 6.77 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 1 hour after 6th and last dose | 38.853 mg/L | Standard Deviation 6.72 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 4: Pre-dose | 3.070 mg/L | Standard Deviation 1.205 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 20 | 0.118 mg/L | Standard Deviation 0.034 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 2 hours after 6th and last dose | 37.361 mg/L | Standard Deviation 8.238 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 2: 1 hour after 2nd dose | 39.536 mg/L | Standard Deviation 7.535 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 16 | 0.720 mg/L | Standard Deviation 0.48 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: 4 hours after 6th and last dose | 35.652 mg/L | Standard Deviation 6.106 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 2: Pre-dose | 2.372 mg/L | Standard Deviation 0.779 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: Pre-dose | 0 mg/L | Standard Deviation 0 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 12 | 3.966 mg/L | Standard Deviation 2.069 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 4 hours after 1st dose | 30.259 mg/L | Standard Deviation 4.921 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 8: Pre-dose | 3.654 mg/L | Standard Deviation 1.539 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 6: 1 hour after 4th dose | 42.200 mg/L | Standard Deviation 15.467 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 0: 2 hours after 1st dose | 33.600 mg/L | Standard Deviation 6.336 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 8: 1 hour after 5th dose | 40.464 mg/L | Standard Deviation 4.432 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 6: Pre-dose | 3.494 mg/L | Standard Deviation 1.44 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 14 | 1.318 mg/L | Standard Deviation 0.419 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 10: Pre-dose | 3.584 mg/L | Standard Deviation 1.859 |
| MOR103 2.0 mg/kg | Mean Serum Concentration of MOR103 Over Time | Week 4: 1 hour after 3rd dose | 37.605 mg/L | Standard Deviation 5.734 |
Secondary
Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses
At the week 0 (first dose) and week 10 (last dose) visits, serum samples were obtained at pre-dose and at 1, 2, and 4 hours after the dose. Tmax values for each patient were calculated based on these data, and the mean Tmax values for the dose cohort are presented here. Because Tmax refers to the time to maximum serum concentration, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable.
Time frame: Week 0 (first dose) and week 10 (last dose)
Population: Pharmocokinetic (PK) analyses were conducted on the PK set, which included all MOR103-treated patients except for 2 patients who discontinued after 2 doses of trial medication (one each in the 1.0 and 2.0 mg/kg groups). PK data for the last dose were missing for one patient in the MOR103 2.0 mg/kg group (n = 7).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOR103 0.5 mg/kg | Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 0 (first dose) | 1.89 hour | Standard Deviation 1.01 |
| MOR103 0.5 mg/kg | Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 10 (last dose) | 2.03 hour | Standard Deviation 0.89 |
| MOR103 1.0 mg/kg | Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 0 (first dose) | 1.49 hour | Standard Deviation 1.12 |
| MOR103 1.0 mg/kg | Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 10 (last dose) | 1.44 hour | Standard Deviation 1.13 |
| MOR103 2.0 mg/kg | Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 0 (first dose) | 1.39 hour | Standard Deviation 0.5 |
| MOR103 2.0 mg/kg | Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses | Week 10 (last dose) | 1.31 hour | Standard Deviation 0.47 |
Secondary
Number of New or Enlarging T2 Lesions
T2-weighted magnetic resonance imaging (MRI) tests were performed at Weeks 8, 12, and 16 to assess the number of new or enlarging T2 brain lesions, a sign of MS activity. MRI images were assessed centrally by Synarc A/S (Hamburg, Germany).
Time frame: Week 8, week 12, and week 16.
Population: MRIs were performed in the safety population (all patients who received at least 1 dose of MOR103 or placebo). However, MRIs at Weeks 12 and 16 were not mandatory per protocol. The number of patients evaluated at Weeks 8, 12, and 16 were:~MOR103 0.5 mg/kg: 8,8,8 MOR103 1.0 m/kg: 6,6,6 MOR103 2.0 mg/kg: 7,7,7 Placebo: 6, 4, 5
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MOR103 0.5 mg/kg | Number of New or Enlarging T2 Lesions | Week 8 | 23 Number of new or enlarging T2 lesions |
| MOR103 0.5 mg/kg | Number of New or Enlarging T2 Lesions | Week 16 | 16 Number of new or enlarging T2 lesions |
| MOR103 0.5 mg/kg | Number of New or Enlarging T2 Lesions | Week 12 | 9 Number of new or enlarging T2 lesions |
| MOR103 1.0 mg/kg | Number of New or Enlarging T2 Lesions | Week 8 | 3 Number of new or enlarging T2 lesions |
| MOR103 1.0 mg/kg | Number of New or Enlarging T2 Lesions | Week 16 | 9 Number of new or enlarging T2 lesions |
| MOR103 1.0 mg/kg | Number of New or Enlarging T2 Lesions | Week 12 | 3 Number of new or enlarging T2 lesions |
| MOR103 2.0 mg/kg | Number of New or Enlarging T2 Lesions | Week 12 | 0 Number of new or enlarging T2 lesions |
| MOR103 2.0 mg/kg | Number of New or Enlarging T2 Lesions | Week 8 | 2 Number of new or enlarging T2 lesions |
| MOR103 2.0 mg/kg | Number of New or Enlarging T2 Lesions | Week 16 | 0 Number of new or enlarging T2 lesions |
| Pooled Placebo | Number of New or Enlarging T2 Lesions | Week 8 | 9 Number of new or enlarging T2 lesions |
| Pooled Placebo | Number of New or Enlarging T2 Lesions | Week 16 | 5 Number of new or enlarging T2 lesions |
| Pooled Placebo | Number of New or Enlarging T2 Lesions | Week 12 | 1 Number of new or enlarging T2 lesions |
Secondary
Number of New T1 Gadolinium-enhancing Lesions
Magnetic resonance imaging (MRI) tests were performed at screening (to confirm subject eligibility) and at Weeks 4, 8, 2, and 16. MRIs at post-screening time points were used to assess the number of new lesions as revealed by gadolinium (Gd) enhancement. Gd-enhanced MRIs reveal new brain lesions reflecting areas of active inflammation. MRI images were assessed centrally by Synarc A/S (Hamburg, Germany).
Time frame: Week 4, week 8, week 12, and week 16.
Population: MRIs were performed in the safety population (all patients who received at least 1 dose of MOR103 or placebo). However, MRIs at Weeks 12 and 16 were not mandatory per protocol. The number of patients evaluated at Weeks 4, 8, 12, and 16 were:~MOR103 0.5 mg/kg: 8,8,8,8 MOR103 1.0 m/kg: 6,6,6,6 MOR103 2.0 mg/kg: 8,7,7,7 Placebo: 6, 6, 4, 5
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MOR103 0.5 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 4 | 8 Number of new T1 Gd-enhancing lesions |
| MOR103 0.5 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 8 | 3 Number of new T1 Gd-enhancing lesions |
| MOR103 0.5 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 12 | 11 Number of new T1 Gd-enhancing lesions |
| MOR103 0.5 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 16 | 8 Number of new T1 Gd-enhancing lesions |
| MOR103 1.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 8 | 2 Number of new T1 Gd-enhancing lesions |
| MOR103 1.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 12 | 3 Number of new T1 Gd-enhancing lesions |
| MOR103 1.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 16 | 6 Number of new T1 Gd-enhancing lesions |
| MOR103 1.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 4 | 1 Number of new T1 Gd-enhancing lesions |
| MOR103 2.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 12 | 1 Number of new T1 Gd-enhancing lesions |
| MOR103 2.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 8 | 1 Number of new T1 Gd-enhancing lesions |
| MOR103 2.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 16 | 1 Number of new T1 Gd-enhancing lesions |
| MOR103 2.0 mg/kg | Number of New T1 Gadolinium-enhancing Lesions | Week 4 | 1 Number of new T1 Gd-enhancing lesions |
| Pooled Placebo | Number of New T1 Gadolinium-enhancing Lesions | Week 16 | 3 Number of new T1 Gd-enhancing lesions |
| Pooled Placebo | Number of New T1 Gadolinium-enhancing Lesions | Week 8 | 3 Number of new T1 Gd-enhancing lesions |
| Pooled Placebo | Number of New T1 Gadolinium-enhancing Lesions | Week 4 | 4 Number of new T1 Gd-enhancing lesions |
| Pooled Placebo | Number of New T1 Gadolinium-enhancing Lesions | Week 12 | 0 Number of new T1 Gd-enhancing lesions |
Secondary
Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples
To assess the potential immunogenicity of MOR103, a central bioanalytical laboratory (Eurofins Medinet BV, Breda, The Netherlands) tested serum samples obtained at baseline and at 3 post-treatment time points (week 14, week 16, and week 20/end of study) for anti-MOR103 antibodies.
Time frame: Baseline, week 14, week 16, and week 20/end of study
Population: All subjects who received 1 or more dose of placebo or MOR103 (safety population). Data were missing for 1 patient each in the MOR103 1.0 mg/kg and 2.0 mg/kg groups at week 14 and week 16. Data were also missing for 1 patient in the placebo group at all post-baseline timepoints (week 14, 16, and 20).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MOR103 0.5 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 16 | 100 percentage of participants |
| MOR103 0.5 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Baseline | 100 percentage of participants |
| MOR103 0.5 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 14 | 100 percentage of participants |
| MOR103 0.5 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 20 | 100 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 20 | 100 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 16 | 100 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Baseline | 100 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 14 | 100 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 14 | 100 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Baseline | 100 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 16 | 100 percentage of participants |
| MOR103 2.0 mg/kg | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 20 | 100 percentage of participants |
| Pooled Placebo | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 14 | 100 percentage of participants |
| Pooled Placebo | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Baseline | 100 percentage of participants |
| Pooled Placebo | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 20 | 100 percentage of participants |
| Pooled Placebo | Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples | Week 16 | 100 percentage of participants |