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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: November 9, 2014
Last verified: November 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
Biological: MOR103
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel 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:
  • 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


Secondary Outcome Measures:
  • 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 Serum Concentration of MOR103 Over Time [ Time Frame: Week 0 (dose 1) to week 20 (end of study) ] [ Designated as safety issue: No ]
    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 [ 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. 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 [ 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. 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 [ 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. 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 [ 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).


Enrollment: 32
Study Start Date: January 2012
Study Completion Date: February 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MOR103 0.5 mg/kg
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).
Biological: MOR103
Anti-GM-CSF monoclonal antibody
Experimental: MOR103 1.0 mg/kg
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).
Biological: MOR103
Anti-GM-CSF monoclonal antibody
Experimental: MOR103 2.0 mg/kg
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).
Biological: MOR103
Anti-GM-CSF monoclonal antibody
Placebo Comparator: Placebo
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).
Other: Placebo
Placebo to anti-GM-CSF monoclonal antibody

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Results First Received: October 8, 2014
Last Updated: November 9, 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
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on November 25, 2014