Phase Ib Study to Evaluate MOR103 in Multiple Sclerosis

NCT01517282 | Completed Phase 1 Results DMC

• 1 other identifier: 2011-001064-22
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 5

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)

  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

  From the first dose (week 0) to study endpoint (week 20)

Secondary Outcomes (7)

• Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples

  Baseline, week 14, week 16, and week 20/end of study

• 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)

• Mean Time to Maximum MOR103 Concentration (Tmax) 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)

Study Arms (4)

MOR103 0.5 mg/kg

EXPERIMENTAL

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

MOR103 1.0 mg/kg

EXPERIMENTAL

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

MOR103 2.0 mg/kg

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

MOR103 BIOLOGICAL

Anti-GM-CSF monoclonal antibody

MOR103 0.5 mg/kg; MOR103 1.0 mg/kg; MOR103 2.0 mg/kg

Placebo OTHER

Placebo to anti-GM-CSF monoclonal antibody

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.
• A patient with any signs of excretory hepatic or kidney dysfunction
• A patient with a positive test for Hepatitis B or Hepatitis C

Sponsors & Collaborators

• MorphoSys AG: lead

Study Sites (5)

Morphosys Investigative Site

Berlin, Germany

Location

Morphosys Investigative Site

Gdansk, Poland

Location

Morphosys Investigative Site

Poznan, Poland

Location

Morhosys Investigative Site

Manchester, United Kingdom

Location

MorphoSys Investigative Site

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Otilimab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Key limitations of this trial include its small sample size and limited duration. Efficacy assessments were not made in this study. Larger clinical trials will be required to evaluate the potential of MOR103 in treating patients with MS.

Results Point of Contact

• Title: Roman Korolkiewicz
• Organization: MorphoSys

roman.korolkiewicz@morphosys.com

+49 89 89927 208

Study Officials

• Roman P Korolkiewicz, MD, PhD

  MorphoSys AG

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2012
• First Posted: January 25, 2012
• Study Start: January 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: February 1, 2014
• Last Updated: November 21, 2014
• Results First Posted: October 13, 2014

Record last verified: 2014-11

Locations

GB (2); PL (2); DE (1)