Back to resultsPhase Ib Study to Evaluate MOR103 in Multiple Sclerosis
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MOR103
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility 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:
- A patient with primary progressive MS (PPMS)
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
- A patient who has not stabilized, in the opinion of the investigator
- 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
- A patient with current or a history of major chronic inflammatory autoimmune diseases other than MS
- A patient with any type of infection
- Patients on chronic prophylactic or suppressive antibiotic, antifungal,or antiviral agents
- A patient with a history of tuberculosis.
- A patient with any signs of excretory hepatic or kidney dysfunction
- A patient with a positive test for Hepatitis B or Hepatitis C
Sites / Locations
- Morphosys Investigative Site
- Morphosys Investigative Site
- Morphosys Investigative Site
- Morhosys Investigative Site
- MorphoSys Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
MOR103 0.5 mg/kg
MOR103 1.0 mg/kg
MOR103 2.0 mg/kg
Placebo
Arm Description
6 doses of MOR103 0.5 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
6 doses of MOR103 1.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
6 doses of MOR103 2.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
6 doses of placebo administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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.
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.
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.
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.
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).
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01517282
Brief Title
Phase Ib Study to Evaluate MOR103 in Multiple Sclerosis
Official Title
A Randomized, Double-blind, Placebo-controlled Phase Ib Study to Evaluate the Safety and Pharmacokinetics of MOR103, a Human Antibody to GM-CSF, in Patients With Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2014
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
February 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MorphoSys AG
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MOR103 0.5 mg/kg
Arm Type
Experimental
Arm Description
6 doses of MOR103 0.5 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
Arm Title
MOR103 1.0 mg/kg
Arm Type
Experimental
Arm Description
6 doses of MOR103 1.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
Arm Title
MOR103 2.0 mg/kg
Arm Type
Experimental
Arm Description
6 doses of MOR103 2.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
6 doses of placebo administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6).
Intervention Type
Biological
Intervention Name(s)
MOR103
Intervention Description
Anti-GM-CSF monoclonal antibody
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo to anti-GM-CSF monoclonal antibody
Primary Outcome Measure Information:
Title
Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)
Description
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)
Secondary Outcome Measure Information:
Title
Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples
Description
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
Title
Mean Serum Concentration of MOR103 Over Time
Description
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)
Title
Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses
Description
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)
Title
Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses
Description
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)
Title
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
Description
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)
Title
Number of New T1 Gadolinium-enhancing Lesions
Description
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.
Title
Number of New or Enlarging T2 Lesions
Description
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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:
A patient with primary progressive MS (PPMS)
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
A patient who has not stabilized, in the opinion of the investigator
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
A patient with current or a history of major chronic inflammatory autoimmune diseases other than MS
A patient with any type of infection
Patients on chronic prophylactic or suppressive antibiotic, antifungal,or antiviral agents
A patient with a history of tuberculosis.
A patient with any signs of excretory hepatic or kidney dysfunction
A patient with a positive test for Hepatitis B or Hepatitis C
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman P Korolkiewicz, MD, PhD
Organizational Affiliation
MorphoSys AG
Official's Role
Study Director
Facility Information:
Facility Name
Morphosys Investigative Site
City
Berlin
Country
Germany
Facility Name
Morphosys Investigative Site
City
Gdansk
Country
Poland
Facility Name
Morphosys Investigative Site
City
Poznan
Country
Poland
Facility Name
Morhosys Investigative Site
City
Manchester
Country
United Kingdom
Facility Name
MorphoSys Investigative Site
City
Nottingham
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Phase Ib Study to Evaluate MOR103 in Multiple Sclerosis
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