Phase Ib Study to Evaluate MOR103 in Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MorphoSys AG
ClinicalTrials.gov Identifier:
NCT01517282
First received: January 10, 2012
Last updated: February 14, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Multiple Sclerosis
Drug: MOR103
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by MorphoSys AG:

Primary Outcome Measures:
  • Incidence and severity of adverse events [ Time Frame: Up to 20 weeks ] [ Designated as safety issue: Yes ]
    To determine the safety of multiple doses of MOR103 in patients with relapsing-remitting or secondary progressive MS (RRMS or SPMS. Safety will be evaluated by assessing adverse events, clinical lab data and vital signs.


Secondary Outcome Measures:
  • Pharmacokinetic profile [ Time Frame: Six time points up to 20 weeks ] [ Designated as safety issue: No ]
    Pharmacokinetic profile assessments comprise of the measuremnt of several standard PK parameters (e.g. Cmax, Tmax, t1/2)

  • Potential immunogenicity of MOR103 [ Time Frame: 4 time points up 20 weeks ] [ Designated as safety issue: No ]
    To determine development of anti-MOR103 antibodies


Enrollment: 30
Study Start Date: December 2011
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1, MOR103, experimental
Biological: MOR103 0.5 mg/kg or placebo
Drug: MOR103
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
Drug: MOR103
MOR103 1.0 mg/kg or placebo iv x 6doses
Experimental: Group 3, MOR103, experimental
Biological: MOR103 2.0 mg/kg or placebo
Drug: MOR103
MOR103 2.0 mg/kg or placebo iv x 6 doses

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

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01517282

Locations
Germany
Morphosys Investigative Site
Berlin, Germany
Poland
Morphosys Investigative Site
Gdansk, Poland
Morphosys Investigative Site
Poznan, Poland
United Kingdom
Morhosys Investigative Site
Manchester, United Kingdom
MorphoSys Investigative Site
Nottingham, United Kingdom
Sponsors and Collaborators
MorphoSys AG
Investigators
Study Director: Roman P Korolkiewicz, MD, PhD MorphoSys AG
  More Information

No publications provided

Responsible Party: MorphoSys AG
ClinicalTrials.gov Identifier: NCT01517282     History of Changes
Other Study ID Numbers: 2011-001064-22
Study First Received: January 10, 2012
Last Updated: February 14, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014