Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, GM-CSF, MOR103
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.
Interventions
DRUGMOR103
MOR103 0.3 mg/kg or placebo iv x 4 doses
Sponsors
MorphoSys AG
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4 | 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. |
| Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8 | 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. |
Countries
Bulgaria, Germany, Netherlands, Poland, Ukraine
Participant flow
Recruitment details
Subjects were recruited and screened between January 19, 2010 and February 9, 2012 at rheumatology centers in Europe (Bulgaria, Germany, the Netherlands, Poland and Ukraine).
Pre-assignment details
Subject eligibility was determined at the screening visit (up to 35 days before treatment initiation) and confirmed at baseline before the first dose on day 1.
Participants by arm
| Arm | Count |
|---|---|
| MOR103 0.3 mg/kg MOR103 0.3 mg/kg IV once weekly for 4 weeks (total of 4 doses) | 24 |
| MOR103 1.0 mg/kg MOR103 1.0 mg/kg IV once weekly for 4 weeks (total of 4 doses) | 22 |
| MOR103 1.5 mg/kg MOR103 1.5 mg/kg IV once weekly for 4 weeks (total of 4 doses) | 23 |
| Pooled Placebo All patients who were randomized to the placebo arms in the 3 study cohorts. Placebo was administered IV once weekly for 4 weeks (total of 4 doses). | 27 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 2 | 3 | 0 | 0 |
| Overall Study | Randomized but not treated | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Pooled Placebo | MOR103 1.5 mg/kg | MOR103 0.3 mg/kg | MOR103 1.0 mg/kg |
|---|---|---|---|---|---|
| Age, Continuous | 53.4 years STANDARD_DEVIATION 11.3 | 53.8 years STANDARD_DEVIATION 12.7 | 53.0 years STANDARD_DEVIATION 9.9 | 57.4 years STANDARD_DEVIATION 8.3 | 49.0 years STANDARD_DEVIATION 12.7 |
| Body mass index | 26.1 kg/m2 STANDARD_DEVIATION 4.1 | 26.3 kg/m2 STANDARD_DEVIATION 3.5 | 25.7 kg/m2 STANDARD_DEVIATION 4.7 | 26.3 kg/m2 STANDARD_DEVIATION 3.6 | 26.1 kg/m2 STANDARD_DEVIATION 4.6 |
| Concomitant medication with non-biologic disease-modifying antirheumatic drugs (DMARDs) Not treated with concomitant non-biologic DMARDs | 10 participants | 1 participants | 2 participants | 2 participants | 5 participants |
| Concomitant medication with non-biologic disease-modifying antirheumatic drugs (DMARDs) Treated with concomitant non-biologic DMARDs | 86 participants | 26 participants | 21 participants | 22 participants | 17 participants |
| Disease Activity Score based on 28 joints and erythrocyte sedimentation rate (DAS28-ESR) | 4.86 units on a scale STANDARD_DEVIATION 0.5 | 4.88 units on a scale STANDARD_DEVIATION 0.41 | 4.87 units on a scale STANDARD_DEVIATION 0.38 | 4.88 units on a scale STANDARD_DEVIATION 0.54 | 4.78 units on a scale STANDARD_DEVIATION 0.66 |
| Prior medication with non-biologic disease-modifying antirheumatic drugs (DMARDs) Not treated with prior non-biologic DMARDs | 22 participants | 6 participants | 3 participants | 6 participants | 7 participants |
| Prior medication with non-biologic disease-modifying antirheumatic drugs (DMARDs) Treated with prior non-biologic DMARDs | 74 participants | 21 participants | 20 participants | 18 participants | 15 participants |
| Prior medication with tumor necrosis factor (TNF) inhibitors Not treated with prior TNF inhibitors | 93 participants | 25 participants | 23 participants | 23 participants | 22 participants |
| Prior medication with tumor necrosis factor (TNF) inhibitors Treated with prior TNF inhibitors | 3 participants | 2 participants | 0 participants | 1 participants | 0 participants |
| Region of Enrollment Bulgaria | 29 participants | 6 participants | 4 participants | 12 participants | 7 participants |
| Region of Enrollment Germany | 17 participants | 4 participants | 2 participants | 4 participants | 7 participants |
| Region of Enrollment Netherlands | 3 participants | 2 participants | 1 participants | 0 participants | 0 participants |
| Region of Enrollment Poland | 23 participants | 8 participants | 3 participants | 8 participants | 4 participants |
| Region of Enrollment Ukraine | 24 participants | 7 participants | 13 participants | 0 participants | 4 participants |
| Rheumatoid factor (RF) status Missing | 2 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Rheumatoid factor (RF) status RF negative | 10 participants | 1 participants | 4 participants | 3 participants | 2 participants |
| Rheumatoid factor (RF) status RF positive | 84 participants | 25 participants | 19 participants | 21 participants | 19 participants |
| Sex: Female, Male Female | 75 Participants | 19 Participants | 18 Participants | 21 Participants | 17 Participants |
| Sex: Female, Male Male | 21 Participants | 8 Participants | 5 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 24 | 22 / 22 | 14 / 23 | 47 / 69 | 12 / 27 |
| serious Total, serious adverse events | 1 / 24 | 0 / 22 | 0 / 23 | 1 / 69 | 1 / 27 |
Outcome results
Primary
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
Population: All patients who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MOR103 0.3 mg/kg | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with treatment-emergent adverse events | 54.2 percentage of participants |
| MOR103 0.3 mg/kg | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with serious adverse events | 4.2 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with treatment-emergent adverse events | 63.6 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with serious adverse events | 0.0 percentage of participants |
| MOR103 1.5 mg/kg | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with treatment-emergent adverse events | 65.2 percentage of participants |
| MOR103 1.5 mg/kg | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with serious adverse events | 0.0 percentage of participants |
| Pooled Active | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with serious adverse events | 1.4 percentage of participants |
| Pooled Active | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with treatment-emergent adverse events | 60.9 percentage of participants |
| Pooled Placebo | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with treatment-emergent adverse events | 44.4 percentage of participants |
| Pooled Placebo | Percentages of Patients With Treatment-emergent or Serious Adverse Events | Percentage with serious adverse events | 3.7 percentage of participants |
Secondary
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)
Population: All treated patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOR103 0.3 mg/kg | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks | -0.2 units on a scale | Standard Deviation 1.1 |
| MOR103 1.0 mg/kg | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks | -1.1 units on a scale | Standard Deviation 0.9 |
| MOR103 1.5 mg/kg | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks | -0.6 units on a scale | Standard Deviation 0.7 |
| Pooled Active | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 4 Weeks | 0.2 units on a scale | Standard Deviation 0.8 |
p-value: 0.095ANCOVA
p-value: <0.0001ANCOVA
p-value: 0.003ANCOVA
Secondary
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)
Time frame: Change from baseline to week 8 (5 weeks after last MOR103 dose)
Population: All treated patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOR103 0.3 mg/kg | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks | -0.3 units on a scale | Standard Deviation 0.9 |
| MOR103 1.0 mg/kg | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks | -1.0 units on a scale | Standard Deviation 1.3 |
| MOR103 1.5 mg/kg | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks | -0.6 units on a scale | Standard Deviation 0.9 |
| Pooled Active | Change From Baseline in Mean Disease Activity Score-28 Joints (DAS28) at 8 Weeks | -0.1 units on a scale | Standard Deviation 0.9 |
p-value: 0.421ANCOVA
p-value: 0.003ANCOVA
p-value: 0.065ANCOVA
Secondary
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.
Time frame: Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8
Population: All treated patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOR103 0.3 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 4 | -1.7 joints | Standard Deviation 2.4 |
| MOR103 0.3 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 8 | -1.9 joints | Standard Deviation 2.2 |
| MOR103 0.3 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 4 | 0.1 joints | Standard Deviation 7.1 |
| MOR103 0.3 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 8 | 0.3 joints | Standard Deviation 5 |
| MOR103 1.0 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 8 | -4.1 joints | Standard Deviation 4.4 |
| MOR103 1.0 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 4 | -4.8 joints | Standard Deviation 3.2 |
| MOR103 1.0 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 8 | -6.8 joints | Standard Deviation 4.1 |
| MOR103 1.0 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 4 | -3.5 joints | Standard Deviation 5.1 |
| MOR103 1.5 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 4 | -3.7 joints | Standard Deviation 6.2 |
| MOR103 1.5 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 8 | -3.3 joints | Standard Deviation 3.1 |
| MOR103 1.5 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 8 | -4.0 joints | Standard Deviation 5.3 |
| MOR103 1.5 mg/kg | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 4 | -3.3 joints | Standard Deviation 3.2 |
| Pooled Active | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 8 | 2.1 joints | Standard Deviation 8 |
| Pooled Active | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 8 | -0.8 joints | Standard Deviation 3.6 |
| Pooled Active | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in swollen joint count at week 4 | 0.1 joints | Standard Deviation 3.5 |
| Pooled Active | Change From Baseline in Mean Swollen and Tender Joint Counts at Weeks 4 and 8 | Change in tender joint count at week 4 | 2.0 joints | Standard Deviation 6.4 |
Secondary
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).
Time frame: Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8
Population: All treated patients
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 4 | -8.6 units on a scale | Standard Deviation 22.8 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 8 | -4.1 units on a scale | Standard Deviation 23.1 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 4 | -0.21 units on a scale | Standard Deviation 0.41 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 8 | -0.21 units on a scale | Standard Deviation 0.56 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 4 | -2.7 units on a scale | Standard Deviation 20.5 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 8 | -4.5 units on a scale | Standard Deviation 21.9 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 4 | 2.7 units on a scale | Standard Deviation 9.2 |
| MOR103 0.3 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 8 | 2.1 units on a scale | Standard Deviation 5.6 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 8 | -13.3 units on a scale | Standard Deviation 24.7 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 4 | -16.6 units on a scale | Standard Deviation 15.6 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 8 | -13.4 units on a scale | Standard Deviation 20.9 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 8 | 9.4 units on a scale | Standard Deviation 12.6 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 4 | 9.1 units on a scale | Standard Deviation 10.2 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 8 | -0.51 units on a scale | Standard Deviation 0.56 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 4 | -0.53 units on a scale | Standard Deviation 0.52 |
| MOR103 1.0 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 4 | -17.4 units on a scale | Standard Deviation 17.2 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 4 | 3.1 units on a scale | Standard Deviation 6 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 4 | -0.31 units on a scale | Standard Deviation 0.24 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 8 | -0.25 units on a scale | Standard Deviation 0.22 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 4 | -6.0 units on a scale | Standard Deviation 17.7 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 8 | -4.0 units on a scale | Standard Deviation 8.3 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 8 | 4.7 units on a scale | Standard Deviation 7.1 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 4 | -11.4 units on a scale | Standard Deviation 11.5 |
| MOR103 1.5 mg/kg | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 8 | -9.5 units on a scale | Standard Deviation 11.9 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 4 | -0.45 units on a scale | Standard Deviation 0.54 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in HAQ-DI at week 8 | -0.44 units on a scale | Standard Deviation 0.54 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 8 | -8.0 units on a scale | Standard Deviation 16.1 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in pain at week 4 | -3.3 units on a scale | Standard Deviation 16.5 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 4 | -3.0 units on a scale | Standard Deviation 16.1 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 8 | 4.3 units on a scale | Standard Deviation 9.1 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in FACIT fatigue score at week 4 | 3.0 units on a scale | Standard Deviation 8.1 |
| Pooled Active | Change From Baseline in Patient-reported Outcomes at Weeks 4 and 8 | Change in patient global assessment at week 8 | -8.2 units on a scale | Standard Deviation 17.5 |
Secondary
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)
Population: All participants were included in ACR response calculations. Patients lacking data required for calculation of an ACR response were considered as not having an ACR response. 1 patient in the MOR103 0.3 mg/kg group, 1 patient in the MOR103 1.0 mg/kg group, and 5 patients in the pooled placebo group had missing data for ACR calculations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MOR103 0.3 mg/kg | Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4 | 25.0 percentage of participants |
| MOR103 1.0 mg/kg | Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4 | 68.2 percentage of participants |
| MOR103 1.5 mg/kg | Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4 | 30.4 percentage of participants |
| Pooled Active | Percentages of Subjects With American College of Rheumatology 20% Improvement (ACR20) at Week 4 | 7.4 percentage of participants |
p-value: 0.243Fisher Exact
p-value: <0.0001Fisher Exact
p-value: 0.135Fisher Exact
Other Pre-specified
Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4
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.
Time frame: Change from screening to week 4 (1 week after last MOR103 dose)
Population: At week 4, MRI data were not available for 5 placebo patients, 2 MOR103 0.3 mg/kg patients, 2 MOR103 1.0 mg/kg patients, and 1 MOR103 1.5 mg/kg patient.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOR103 0.3 mg/kg | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4 | -0.37 units on a scale | Standard Deviation 3.09 |
| MOR103 1.0 mg/kg | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4 | -1.50 units on a scale | Standard Deviation 2.87 |
| MOR103 1.5 mg/kg | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4 | -0.50 units on a scale | Standard Deviation 2.22 |
| Pooled Active | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 4 | -0.66 units on a scale | Standard Deviation 3.09 |
Other Pre-specified
Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at 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.
Time frame: Change from screening to week 8
Population: At week 8, MRI data were not available for 6 placebo patients, 5 MOR103 0.3 mg/kg patients, 1 MOR103 1.0 mg/kg patient, and 2 MOR103 1.5 mg/kg patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOR103 0.3 mg/kg | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8 | -0.48 units on a scale | Standard Deviation 3.49 |
| MOR103 1.0 mg/kg | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8 | -0.90 units on a scale | Standard Deviation 2.83 |
| MOR103 1.5 mg/kg | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8 | -1.00 units on a scale | Standard Deviation 2.73 |
| Pooled Active | Change From Screening in Outcome Measures in Rheumatology (OMERACT)-Rheumatoid Arthritis Magnetic Resonance Imaging Studies Mean Sum Score for Synovitis at Week 8 | -0.91 units on a scale | Standard Deviation 3.06 |