Phase Ib Study to Evaluate MOR103 in Multiple Sclerosis
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|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|
- Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From the first dose (week 0) to study endpoint (week 20) ] [ Designated as safety issue: Yes ]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
- Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples [ Time Frame: Baseline, week 14, week 16, and week 20/end of study ] [ Designated as safety issue: No ]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 Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses [ Time Frame: Week 0 (first dose) and week 10 (last dose) ] [ Designated as safety issue: No ]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. Mean Cmax values for each dose cohort were directly calculated from these samples.
- Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses [ Time Frame: Week 0 (first dose) and week 10 (last dose) ] [ Designated as safety issue: No ]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. Mean Tmax values for each dose cohort were directly calculated from these samples.
- 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 [ Time Frame: Week 0 (first dose) and week 10 (last dose) ] [ Designated as safety issue: No ]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.
- Number of New T1 Gadolinium-enhancing Lesions [ Time Frame: Week 4, week 8, week 12, and week 16. ] [ Designated as safety issue: No ]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 [ Time Frame: Week 8, week 12, and week 16. ] [ Designated as safety issue: No ]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).
|Study Start Date:||December 2011|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Experimental: Group 1, MOR103, experimental
Biological: MOR103 0.5 mg/kg or placebo
Group1: MOR103 0.5 mg/kg or placebo iv x 6 doses
Experimental: Group 2, MOR103, experimental
Biological: MOR103 1.0 mg/kg or placebo
MOR103 1.0 mg/kg or placebo iv x 6doses
Experimental: Group 3, MOR103, experimental
Biological: MOR103 2.0 mg/kg or placebo
MOR103 2.0 mg/kg or placebo iv x 6 doses
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01517282
|Morphosys Investigative Site|
|Morphosys Investigative Site|
|Morphosys Investigative Site|
|Morhosys Investigative Site|
|Manchester, United Kingdom|
|MorphoSys Investigative Site|
|Nottingham, United Kingdom|
|Study Director:||Roman P Korolkiewicz, MD, PhD||MorphoSys AG|