Clinical trial NCT01023256: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
GM-CSF
MOR103
Lead sponsor: MorphoSys AG
Sponsor class: INDUSTRY
First posted: 2009-12-02
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentages of Patients With Treatment-emergent or Serious Adverse Events
timeFrame: From the first dose through the 16-week visit
Secondary outcomes:
measure: Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks
timeFrame: Change from baseline to week 4 (1 week after last MOR103 dose)
measure: Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks
timeFrame: Change from baseline to week 8 (5 weeks after last MOR103 dose)
measure: Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4
timeFrame: Week 4 (1 week after last MOR103 dose)
measure: Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8
timeFrame: Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8
measure: Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8
timeFrame: Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8
Other outcomes:
measure: Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4
timeFrame: Change from screening to week 4 (1 week after last MOR103 dose)
measure: Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8
timeFrame: Change from screening to week 8
Locations:
city: MorphoSys Investigative sites
country: Bulgaria
facility: MorphoSys Investigative sites
city: MorphoSys Investigative sites
country: Germany
facility: MorphoSys Investigative sites
city: MorphoSys Investigative sites
country: Netherlands
facility: MorphoSys Investigative sites
city: MorphoSys Investigative sites
country: Poland
facility: MorphoSys Investigative sites
city: MorphoSys investigatíve sites
country: Ukraine
facility: MorphoSys Investigative sites
Study officials:
affiliation: MorphoSys AG
name: Roman P Korolkiewicz, MD, PhD
role: STUDY_DIRECTOR
References:
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.