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

MorphoSys AG96 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

MOR103DRUG

MOR103 0.3 mg/kg or placebo iv x 4 doses

MOR103DRUG

MOR103 1.0 mg/kg or placebo iv x 4 doses

MOR103DRUG

MOR103 1.5 mg/kg or placebo iv x 4 doses

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (5)

MorphoSys Investigative sites

MorphoSys Investigative Sites, Bulgaria

MorphoSys Investigative sites

MorphoSys Investigative Sites, Germany

MorphoSys Investigative sites

MorphoSys Investigative Sites, Netherlands

MorphoSys Investigative sites

MorphoSys Investigative Sites, Poland

Outcomes

Primary Outcomes

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.

Time frame: From the first dose through the 16-week visit

Secondary Outcomes

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).

Time frame: 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

Time frame: 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.

Time frame: Week 4 (1 week after last MOR103 dose)

Data from ClinicalTrials.gov

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