Rheumatoid arthritis MedDRA version: 13.1 Level: LLT Classification code 10003268 Term: Arthritis rheumatoid System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: MOR103
Product Code: MOR103
Pharmaceutical Form: Solution for infusion
Current Sponsor code: MOR103
Other descriptive name: Human Recombinant IgG1, lambda
Concentration unit: mg/ml milli
Sponsors
MorphoSys AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Outpatients > 18 years of age 2. BMI between 19.0 and 35.0 kg/m2 (extremes included). 3. Diagnosis of rheumatoid arthritis (RA), according to the revised criteria of the American College of Rheumatology (ACR), 1987. 4. Active disease at screening defined as: - At least 3 swollen and 3 tender joints with at least 1 swollen joint involvement of the hand excluding the proximal interphalangeal (PIP) joint (using the DAS28 joint count). - Elevated CRP level > 5 mg/l (in RF and anti-CCP sero-negative patients) or > 2 mg/l (in RF and/or anti-CCP sero-positive patients). - disease activity score "DAS28" =65 years) yes F.1.3.1 Number of subjects for this age range 89
Exclusion criteria
Exclusion criteria: 1. Previous treatment with immunosuppressive agents and non-compliance with min wash-out periods required prior to first dosing of study drug: 1m for etanercerpt, anakinra, ciclosporin, MMF, tacrolimus; 2m for adalimumab and certolizumab and 3m for infliximab, abatacept, golimumab and tocilizumab 2. Previous treatment with rituximab within 9m prior to first dose of study drug 3. History of therapy with cell depleting agent(s) incl. IMPs (Campath, anti-CD3, -CD4, -CD5, -CD11a, -CD19, -CD22, -Blys/BAFF) 4. Any therapy with human, chimeric or murine Abs (except for above) or any experimental therapy within 3m or 5 half-lives (whichever is longer) prior to screening 5. In case patient has been discontinued from other DMARDs due to toxicity or lack of efficacy, time since last dose at least 1m and effects of that agent should have dissipated as indicated by recognized duration of effect (e.g. hydroxychloroquine, sulfasalazine), or standard wash-out procedure (cholestyramine for leflunomide) 6. Patients who received systemic steroids, epidural steroid injections, intra-articular or systemic corticosteroid injections within 4w before screening 7. Known allergy to murine, chimeric or human antibodies 8. Body weight >150 kg 9. History of anaphylaxis/severe anaphylactic reaction/shock to any drug administered parentarally & suspected allergies to protein based therapeutics. In all other cases, subjects should be pre-treated with anti-histamines and H-1 receptor inhibitors 10. Pregnant/breast-feeding women & pre-menopausal women not receiving methotrexate or leflunomide a/o not willing to use at least 2 methods of effective contraception during and for a specific period after studyparticipation 11. Any findings indicative of tuberculosis or history of tuberculosis or a positive PPD- or tuberculosis ELISA test at screening 12. Presence or history of major chronic inflammatory autoimmune diseases 13. Positive hepatitis B surface antigen (HBs-Ag)test, hepatitis C (anti HCV antibody) test a/o confirmed HIV infection 14. Any type of infection requiring use of antibiotics & which does not resolve completely within 3w before sudy drug administration 15. History of recurrent pulmonary infections , recurrent abscesses, intra-abdominal infections or chronic infections 16. Procalcitonin serum level >0.5 ng/ml at screening 17. IgG level below lower limit of reference range at screening 18. History of reactivation of Epstein Barr (EB) viral infection or >1,000 EBV genome equivalent/10E6 cells in peripheral blood mononuclear cell preparations 19. History of malignancy with exception of basal cell/squamous cell carcinoma of skin/carcinoma of cervix successfully treated within the last 3y 20.Significant cardiac disease on ECG 21. History of severe pulmonary disease 22. WBC /= 1.5xULN) or renal insufficiency (creatinine clr/EGFR 2x upper limit of reference range at screening 25. Live vaccines within 8w of study drug administration 26. Presence of contra-indications to MRI or contrast agents 27. Any condition/laboratory findings/medical history/pre-study assessments, that in the opinion of the investigator constitute a risk or a contra-indication for the patient'
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety and tolerability of multiple doses of MOR103 in patients with active rheumatoid arthritis.;Secondary Objective: 1. Signs of efficacy 2. Pharmcokinetics of multiple doses 3. Potential immunogenicity;Primary end point(s): Safety and tolerability of MOR103 as assessed by the safety measures.;Timepoint(s) of evaluation of this end point: At end of each cohort and at the end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in the DAS28 score from baseline to Days 29 and 57 2. Proportion of patients achieving ACR20, ACR50, and ACR70 response on Day 29 and Day 57. 3. EULAR28 responder index on Day 29 and Day 57 (compared to baseline). 5. Change in individual components of the ACR core set of measures from baseline to Day 29 and Day 57. 5. Change from screening to Day 29 and Day 57 of the joint scoring on MRI according to the Rheumatoid Arthritis MRI Scoring system (RAMRIS) for synovitis and bone edema. 6. Immunogenicity of MOR103 (anti-MOR103 antibodies) 7. Pharmacokinetics (PK) endpoint: MOR103 serum concentrations and PK parameters (trough levels after each dose, exposure and terminal elimination after the last dose, accumulation and dose proportionality based on estimated AUCtau) 8. Health Assessment Questionnaire (HAQ), SF36, FACIT-F questionaires ;Timepoint(s) of evaluation of this end point: At the end of study | — |
Countries
Bulgaria, Germany, Netherlands, Poland, Ukraine
Contacts
Public ContactRoman Korolkiewicz
MorphoSys AG
Outcome results
None listed