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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Multiple Sclerosis
- Sponsor
- MorphoSys AG
- Enrollment
- 32
- Locations
- 3
- Primary Endpoint
- Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)
- Status
- Completed
- Last Updated
- 11 years ago
Overview
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.
Investigators
Eligibility Criteria
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
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.
Outcomes
Primary Outcomes
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)
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 Outcomes
- Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples(Baseline, week 14, week 16, and week 20/end of study)
- Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses(Week 0 (first dose) and week 10 (last dose))
- Number of New T1 Gadolinium-enhancing Lesions(Week 4, week 8, week 12, and week 16.)
- Mean Serum Concentration of MOR103 Over Time(Week 0 (dose 1) to week 20 (end of study))
- Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses(Week 0 (first dose) and week 10 (last dose))
- 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))
- Number of New or Enlarging T2 Lesions(Week 8, week 12, and week 16.)