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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: MOR103
* Drug: MOR103
* Drug: MOR103


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: MOR103, experimental<br>Biological: MOR103 0.3 mg/kg or placebo | Drug: MOR103<br>* MOR103 0.3 mg/kg or placebo iv x 4 doses<br>|
| Experimental: Group 2: MOR103, experimental<br>Biological: MOR103 1.0 mg/kg or placebo | Drug: MOR103<br>* MOR103 1.0 mg/kg or placebo iv x 4 doses<br>|
| Experimental: Group 3: MOR103, experimental<br>Biological: MOR103 1.5 mg/kg or placebo | Drug: MOR103<br>* MOR103 1.5 mg/kg or placebo iv x 4 doses<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, GM-CSF, MOR103