Clinical trial NCT01517282: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Lead sponsor: MorphoSys AG
Sponsor class: INDUSTRY
First posted: 2012-01-25
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

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

Primary outcomes:
measure: Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From the first dose (week 0) to study endpoint (week 20)
Secondary outcomes:
measure: Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples
timeFrame: Baseline, week 14, week 16, and week 20/end of study
measure: Mean Serum Concentration of MOR103 Over Time
timeFrame: Week 0 (dose 1) to week 20 (end of study)
measure: Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses
timeFrame: Week 0 (first dose) and week 10 (last dose)
measure: Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses
timeFrame: Week 0 (first dose) and week 10 (last dose)
measure: 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
timeFrame: Week 0 (first dose) and week 10 (last dose)
measure: Number of New T1 Gadolinium-enhancing Lesions
timeFrame: Week 4, week 8, week 12, and week 16.
measure: Number of New or Enlarging T2 Lesions
timeFrame: Week 8, week 12, and week 16.
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Morphosys Investigative Site
city: Gdansk
country: Poland
facility: Morphosys Investigative Site
city: Poznan
country: Poland
facility: Morphosys Investigative Site
city: Manchester
country: United Kingdom
facility: Morhosys Investigative Site
city: Nottingham
country: United Kingdom
facility: MorphoSys Investigative Site
Study officials:
affiliation: MorphoSys AG
name: Roman P Korolkiewicz, MD, PhD
role: STUDY_DIRECTOR
References: