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

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ClinicalTrials.gov Identifier: NCT01023256
Recruitment Status : Completed
First Posted : December 2, 2009
Results First Posted : May 8, 2014
Last Update Posted : October 24, 2014
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: MOR103 Phase 1 Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : December 2009
Actual Primary Completion Date : June 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group 1: MOR103, experimental
Biological: MOR103 0.3 mg/kg or placebo
Drug: MOR103
MOR103 0.3 mg/kg or placebo iv x 4 doses

Experimental: Group 2: MOR103, experimental
Biological: MOR103 1.0 mg/kg or placebo
Drug: MOR103
MOR103 1.0 mg/kg or placebo iv x 4 doses

Experimental: Group 3: MOR103, experimental
Biological: MOR103 1.5 mg/kg or placebo
Drug: MOR103
MOR103 1.5 mg/kg or placebo iv x 4 doses




Primary Outcome Measures :
  1. Percentages of Patients With Treatment-emergent or Serious Adverse Events [ Time Frame: 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 :
  1. Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks [ Time Frame: 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).

  2. 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) ]
    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)

  3. Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4 [ Time Frame: 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.

  4. Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 [ Time Frame: 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.

  5. Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 [ Time Frame: 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).


Other Outcome Measures:
  1. Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4 [ Time Frame: Change from screening to week 4 (1 week after last MOR103 dose) ]
    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.

  2. Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8 [ Time Frame: Change from screening to week 8 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01023256


Locations
Bulgaria
MorphoSys Investigative sites
MorphoSys Investigative sites, Bulgaria
Germany
MorphoSys Investigative sites
MorphoSys Investigative sites, Germany
Netherlands
MorphoSys Investigative sites
MorphoSys Investigative sites, Netherlands
Poland
MorphoSys Investigative sites
MorphoSys Investigative sites, Poland
Ukraine
MorphoSys Investigative sites
MorphoSys investigatíve sites, Ukraine
Sponsors and Collaborators
MorphoSys AG
Investigators
Study Director: Roman P Korolkiewicz, MD, PhD MorphoSys AG

Publications of Results:
Responsible Party: MorphoSys AG
ClinicalTrials.gov Identifier: NCT01023256     History of Changes
Other Study ID Numbers: MSC-1001
First Posted: December 2, 2009    Key Record Dates
Results First Posted: May 8, 2014
Last Update Posted: October 24, 2014
Last Verified: October 2014

Keywords provided by MorphoSys AG:
Rheumatoid arthritis
GM-CSF
MOR103

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases