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

Phase 1

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: MOR103

Registration Number: NCT01023256

Lead Sponsor: MorphoSys AG

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 96

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Group 2: MOR103, experimental	MOR103	Biological: MOR103 1.0 mg/kg or placebo
Group 3: MOR103, experimental	MOR103	Biological: MOR103 1.5 mg/kg or placebo
Group 1: MOR103, experimental	MOR103	Biological: MOR103 0.3 mg/kg or placebo

Primary Outcome Measures

Name	Time	Method
Percentages of Patients With Treatment-emergent or Serious Adverse Events	From the first dose through the 16-week visit	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

Name	Time	Method
Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4	Week 4 (1 week after last MOR103 dose)	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	Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 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	Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 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 in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks	Change from baseline to week 4 (1 week after last MOR103 dose)	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	Change from baseline to week 8 (5 weeks after last MOR103 dose)	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)