Back to resultsSafety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MOR103
MOR103
MOR103
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, GM-CSF, MOR103
Eligibility Criteria
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
Sites / Locations
- MorphoSys Investigative sites
- MorphoSys Investigative sites
- MorphoSys Investigative sites
- MorphoSys Investigative sites
- MorphoSys Investigative sites
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group 1: MOR103, experimental
Group 2: MOR103, experimental
Group 3: MOR103, experimental
Arm Description
Biological: MOR103 0.3 mg/kg or placebo
Biological: MOR103 1.0 mg/kg or placebo
Biological: MOR103 1.5 mg/kg or placebo
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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 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)
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.
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 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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01023256
Brief Title
Safety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
December 2009 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MorphoSys AG
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, GM-CSF, MOR103
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
96 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: MOR103, experimental
Arm Type
Experimental
Arm Description
Biological: MOR103 0.3 mg/kg or placebo
Arm Title
Group 2: MOR103, experimental
Arm Type
Experimental
Arm Description
Biological: MOR103 1.0 mg/kg or placebo
Arm Title
Group 3: MOR103, experimental
Arm Type
Experimental
Arm Description
Biological: MOR103 1.5 mg/kg or placebo
Intervention Type
Drug
Intervention Name(s)
MOR103
Intervention Description
MOR103 0.3 mg/kg or placebo iv x 4 doses
Intervention Type
Drug
Intervention Name(s)
MOR103
Intervention Description
MOR103 1.0 mg/kg or placebo iv x 4 doses
Intervention Type
Drug
Intervention Name(s)
MOR103
Intervention Description
MOR103 1.5 mg/kg or placebo iv x 4 doses
Primary Outcome Measure Information:
Title
Percentages of Patients With Treatment-emergent or Serious Adverse Events
Description
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.
Time Frame
From the first dose through the 16-week visit
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks
Description
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).
Time Frame
Change from baseline to week 4 (1 week after last MOR103 dose)
Title
Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks
Description
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)
Time Frame
Change from baseline to week 8 (5 weeks after last MOR103 dose)
Title
Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4
Description
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.
Time Frame
Week 4 (1 week after last MOR103 dose)
Title
Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8
Description
Swollen joint counts were based on 66 joints and tender joint counts were based on 69 joints.
Time Frame
Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8
Title
Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8
Description
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).
Time Frame
Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8
Other Pre-specified Outcome Measures:
Title
Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4
Description
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.
Time Frame
Change from screening to week 4 (1 week after last MOR103 dose)
Title
Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8
Description
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.
Time Frame
Change from screening to week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman P Korolkiewicz, MD, PhD
Organizational Affiliation
MorphoSys AG
Official's Role
Study Director
Facility Information:
Facility Name
MorphoSys Investigative sites
City
MorphoSys Investigative sites
Country
Bulgaria
Facility Name
MorphoSys Investigative sites
City
MorphoSys Investigative sites
Country
Germany
Facility Name
MorphoSys Investigative sites
City
MorphoSys Investigative sites
Country
Netherlands
Facility Name
MorphoSys Investigative sites
City
MorphoSys Investigative sites
Country
Poland
Facility Name
MorphoSys Investigative sites
City
MorphoSys investigatíve sites
Country
Ukraine
12. IPD Sharing Statement
Citations:
PubMed Identifier
24534756
Citation
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.
Results Reference
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Safety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis
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