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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01023256
• Other study ID #: MSC-1001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 19, 2009
• Last updated: October 15, 2014
• Start date: December 2009
• Est. completion date: June 2012

Study information

• Verified date: October 2014
• Source: MorphoSys AG
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Paul-Ehrlich-InstitutBulgaria: Bulgarian Drug AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsUkraine: Ministry of Health
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• MOR103
MOR103 0.3 mg/kg or placebo iv x 4 doses
• MOR103
MOR103 1.0 mg/kg or placebo iv x 4 doses
• MOR103
MOR103 1.5 mg/kg or placebo iv x 4 doses

Locations

Country	Name	City	State
Bulgaria	MorphoSys Investigative sites	MorphoSys Investigative sites
Germany	MorphoSys Investigative sites	MorphoSys Investigative sites
Netherlands	MorphoSys Investigative sites	MorphoSys Investigative sites
Poland	MorphoSys Investigative sites	MorphoSys Investigative sites
Ukraine	MorphoSys Investigative sites	MorphoSys investigatíve sites

Sponsors (1)

Lead Sponsor	Collaborator
MorphoSys AG

Countries where clinical trial is conducted

Bulgaria,  Germany,  Netherlands,  Poland,  Ukraine, 

References & Publications (1)

Behrens F, Tak PP, Østergaard 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 monocl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	Change from screening to week 4 (1 week after last MOR103 dose)	No
Other	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.	Change from screening to week 8	No
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.	From the first dose through the 16-week visit	Yes
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).	Change from baseline to week 4 (1 week after last MOR103 dose)	No
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)	Change from baseline to week 8 (5 weeks after last MOR103 dose)	No
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.	Week 4 (1 week after last MOR103 dose)	No
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.	Change from baseline to week 4 (1 week after last MOR103 dose) and change from baseline to week 8	No
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).	Change from baseline at week 4 (1 week after last MOR103 dose) and change from baseline at week 8	No