Rheumatoid ArthritisPhase 1/2NCT01023256
Safety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis
A Phase 1/2 study testing MOR103 in people with Rheumatoid Arthritis, run by MorphoSys AG at 5 sites in 5 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- MOR103
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Dec 2009to Jun 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Netherlands1 site
MorphoSys Investigative sites
MorphoSys Investigative Sites
About this study
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
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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- MOR103
- Keywords
- Rheumatoid arthritis, GM-CSF, MOR103
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| Group 1: MOR103, experimental | Experimental | Biological: MOR103 0.3 mg/kg or placebo Receives: Drug: MOR103 |
| Group 2: MOR103, experimental | Experimental | Biological: MOR103 1.0 mg/kg or placebo Receives: Drug: MOR103 |
| Group 3: MOR103, experimental | Experimental | Biological: MOR103 1.5 mg/kg or placebo Receives: Drug: MOR103 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From the first dose through the 16-week visit
Secondary outcomes (5)
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).
Measured: 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
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)
Measured: 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.
Measured: Week 4 (1 week after last MOR103 dose)
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.
Measured: Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8
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).
Measured: Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2009 (estimated)
- Study startDec 2009
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- MorphoSys AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Roman P Korolkiewicz, MD, PhD, Study director, MorphoSys AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01023256
- Sponsor's protocol ID
- MSC-1001
- Status last verified
- Oct 2014
- First submitted
- 19 Nov 2009
- Last updated
- 24 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24534756
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01023256
- Acronym / sponsor ID
- MSC-1001
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, GM-CSF, MOR103
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- MorphoSys AGIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 2 Dec 2009 (estimated)
- Results
- Posted 8 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: MOR103, experimental | Experimental | Drug: MOR103Biological: MOR103 0.3 mg/kg or placebo |
| Group 2: MOR103, experimental | Experimental | Drug: MOR103Biological: MOR103 1.0 mg/kg or placebo |
| Group 3: MOR103, experimental | Experimental | Drug: MOR103Biological: MOR103 1.5 mg/kg or placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MOR103MOR103 0.3 mg/kg or placebo iv x 4 doses | Drug | Group 1: MOR103, experimental |
| MOR103MOR103 1.0 mg/kg or placebo iv x 4 doses | Drug | Group 2: MOR103, experimental |
| MOR103MOR103 1.5 mg/kg or placebo iv x 4 doses | Drug | Group 3: MOR103, experimental |
Primary outcome
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.
5 secondary outcomes
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)
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
Time frame: Week 4 (1 week after last MOR103 dose)
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24534756Behrens 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roman P Korolkiewicz, MD, PhD study director
MorphoSys AG
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MOR103 in people with Rheumatoid Arthritis, run by MorphoSys AG at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Bulgaria, Germany, Netherlands, Poland, Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentages of Patients With Treatment-emergent or Serious Adverse Events (time frame: From the first dose through the 16-week visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01023256, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2014.