Safety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis

A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Preliminary Clinical Activity and Immunogenicity of Multiple Doses of MOR103 Administered Intravenously to Patients With Active Rheumatoid Arthritis

GM-CSF is considered to have a key role in the initiation and progression of arthritic inflammation. The purpose of this study is to evaluate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of multiple doses of MOR103, a human antibody to GM-CSF, in patients with active rheumatoid arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: MOR103; Drug: MOR103; Drug: MOR103

Detailed Description

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects 0.5% to 1% of the adult population world wide. RA primarily affects the joints and is characterized by chronic inflammation of the synovial tissue, which eventually leads to the destruction of cartilage, bone and ligaments and can cause joint deformity.

Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-6 and granulocyte macrophage colony stimulating factor (GM-CSF), which lead to the activation and proliferation of immune cells, are found to be increased in the inflamed joint. Several preclinical findings support an anti-GM-CSF therapy for RA.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • MorphoSys Investigative sites, Bulgaria
    • MorphoSys Investigative sites
• Germany
  • MorphoSys Investigative sites, Germany
    • MorphoSys Investigative sites
• Netherlands
  • MorphoSys Investigative sites, Netherlands
    • MorphoSys Investigative sites
• Poland
  • MorphoSys Investigative sites, Poland
    • MorphoSys Investigative sites
• Ukraine
  • MorphoSys investigatíve sites, Ukraine
    • MorphoSys Investigative sites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Rheumatoid arthritis (RA) per revised 1987 ACR criteria
• Active RA: ≥3 swollen and 3 tender joints with at least 1 swollen joint in the hand, excluding the PIP joint
• CRP > 5.0 mg/L (RF and anti-CCP seronegative); CRP >2 mg/l (RF and/or anti-CCP seropositive)
• DAS28 ≤ 5.1
• Stable regimen of concomitant RA therapy (NSAIDs, steroids, non- biological DMARDs).
• Negative PPD tuberculin skin test

Exclusion Criteria:

• Previous therapy with B or T cell depleting agents other than Rituximab (e.g. Campath). Prior treatment with Rituximab, TNF-inhibitors, other biologics (e.g. anti-IL-1 therapy) and systemic immunosuppressive agents is allowed with a washout period.
• Any history of ongoing, significant or recurring infections
• Any active inflammatory diseases other than RA
• Treatment with a systemic investigational drug within 6 months prior to screening
• Women of childbearing potential, unless receiving stable doses of methotrexate or leflunomide
• Significant cardiac or pulmonary disease (including methotrexate- associated lung toxicity)
• Hepatic or renal insufficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: MOR103, experimental; Biological: MOR103 0.3 mg/kg or placebo	Drug: MOR103; MOR103 0.3 mg/kg or placebo iv x 4 doses; Drug: MOR103; MOR103 1.0 mg/kg or placebo iv x 4 doses; Drug: MOR103; MOR103 1.5 mg/kg or placebo iv x 4 doses
Experimental: Group 2: MOR103, experimental; Biological: MOR103 1.0 mg/kg or placebo	Drug: MOR103; MOR103 0.3 mg/kg or placebo iv x 4 doses; Drug: MOR103; MOR103 1.0 mg/kg or placebo iv x 4 doses; Drug: MOR103; MOR103 1.5 mg/kg or placebo iv x 4 doses
Experimental: Group 3: MOR103, experimental; Biological: MOR103 1.5 mg/kg or placebo	Drug: MOR103; MOR103 0.3 mg/kg or placebo iv x 4 doses; Drug: MOR103; MOR103 1.0 mg/kg or placebo iv x 4 doses; Drug: MOR103; MOR103 1.5 mg/kg or placebo iv x 4 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Patients With Treatment-emergent or Serious Adverse Events	Data on treatment-emergent adverse events (MedDRA version 13.0) were collected at each visit (weeks 1, 2, 3, 4, 5, 6, 8, 10, 13, and 16). For a list of serious adverse events and adverse events occurring at a frequency of >5 % (>1 patient) in any treatment group, please see the adverse events listing.	From the first dose through the 16-week visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks	The primary exploratory efficacy outcome was change from baseline in Disease Activity Score calculated using 28 joints (DAS28) and the erythrocyte sedimentation rate (ESR) as the acute phase reactant (0 = no disease activity; 9.3 = maximal disease activity).	Change from baseline to week 4 (1 week after last MOR103 dose)
Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks	The primary exploratory efficacy outcome was change from baseline in Disease Activity Score calculated using 28 joints (DAS28) and the erythrocyte sedimentation rate (ESR) as the acute phase reactant (0 = no disease activity; 9.3 = maximal disease activity)	Change from baseline to week 8 (5 weeks after last MOR103 dose)
Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4	The percentage of patients achieving an ACR20 response (20% improvement based on ACR improvement criteria) in each group. ACR20 improvement criteria require at least 20% improvement in both swollen and tender joints counts and 3 out of 5 of the following parameters: pain visual analog scale, patient global assessment, physician global assessment, acute phase reactant (erythrocyte sedimentation rate or C-reactive protein), and functional questionnaire.	Week 4 (1 week after last MOR103 dose)
Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8	Swollen joint counts were based on 66 joints and tender joint counts were based on 69 joints.	Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8
Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8	Patient-reported outcomes included patient's self-assessment of pain (measured on a 100 mm visual analogue scale [VAS] from 0 = best to 100 = worst), the Health Assessment Questionnaire-Disability Index (HAQ-DI; 0 = best to 3 = worst), the patient's global assessment of disease activity (measured on a 100 mm visual analogue scale [VAS] from 0 = best to 100 = worst), and fatigue, which was measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue self-assessment scale (0 = worst; 52 = best).	Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4	Magnetic resonance imaging (MRI) was performed on the wrist and hand on the side with the most swollen joints (or the right side if swollen joints were equivalent). The 2nd to 5th metacarpophalangeal joints and 3 wrist joints (distal radioulnar, radiocarpal, and intercarpal-carpometacarpal joints) were scored on a scale of 0 = no synovitis to 3 = severe synovitis. MRIs were scored by 2 independent experts blinded to patient data and chronology. The sum score is the average of the 2 reader scores for each of the 7 joints. The range of the sum score is thus 0 = no synovitis in any joint to 21 = severe synovitis in all joints.	Change from screening to week 4 (1 week after last MOR103 dose)
Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8	Magnetic resonance imaging (MRI) was performed on the wrist and hand on the side with the most swollen joints (or the right side if swollen joints were equivalent). The 2nd to 5th metacarpophalangeal joints and 3 wrist joints (distal radioulnar, radiocarpal, and intercarpal-carpometacarpal joints) were scored on a scale of 0 = no synovitis to 3 = severe synovitis. MRIs were scored by 2 independent experts blinded to patient data and chronology. The sum score is the average of the 2 reader scores for each of the 7 joints. The range of the sum score is thus 0 = no synovitis in any joint to 21 = severe synovitis in all joints.	Change from screening to week 8

Collaborators and Investigators

• Sponsor: MorphoSys AG
• Investigators: Study Director: Roman P Korolkiewicz, MD, PhD, MorphoSys AG

Publications and helpful links

General Publications

• Behrens F, Tak PP, Ostergaard M, Stoilov R, Wiland P, Huizinga TW, Berenfus VY, Vladeva S, Rech J, Rubbert-Roth A, Korkosz M, Rekalov D, Zupanets IA, Ejbjerg BJ, Geiseler J, Fresenius J, Korolkiewicz RP, Schottelius AJ, Burkhardt H. MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis. 2015 Jun;74(6):1058-64. doi: 10.1136/annrheumdis-2013-204816. Epub 2014 Feb 17.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: November 19, 2009
• First Submitted That Met QC Criteria: December 1, 2009
• First Posted (Estimate): December 2, 2009

Study Record Updates

• Last Update Posted (Estimate): October 24, 2014
• Last Update Submitted That Met QC Criteria: October 15, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Rheumatoid arthritis; GM-CSF; MOR103
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: MSC-1001