Adult patients with Familial Mediterranean Fever, who have active disease MedDRA version: 20.0 Level: PT Classification code 10016207 Term: Familial mediterranean fever System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: RoActemra® 20mg/ml Konzentrat
Tocilizumab
Pharmaceutical Form:
INN or Proposed INN: INN-Tocilizumab
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentration unit: mg/kg m
Sponsors
University Hospital Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years and written informed consent - FMF according to the Tel Hashomer Criteria (Appendix); with at least one heterozygous or homozygous mutation of the MEFV gene - Inadequate response or intolerance to colchicine - Attack during the last 12 weeks, defined as episodes of fever and/or pericarditis and/or serositis and/or testis involvement and/or arthritis and/or erysipelas-like rash and - CRP >0.5mg/dl and/or ESR >20mm/h and/or SAA >10mg/dl - Physician Global Assessment (PGA) >2 - Able and willing to provide written informed consent and to comply with the study protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects presenting with any of the following criteria will not be included in the trial: - Age 10mg/day within 1 week; prednisolone = 10mg/day can be given on a stable dose throughout the study - Analgesic medication other than paracetamol or ibuprofen or diclofenac, which can be used at a stable dose and for treatment of FMF attacks. - Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening - Treatment with Anakinra within the last 1 week prior to baseline (ptb), Canakinumab within the last 8 week prior to baseline - Treatment with etanercept within 2 weeks; certolizumab pegol, abatacept or adalimumab within 6 weeks; golimumab and infliximab within 8 weeks ptb - Rituximab within 24 weeks ptb - Leflunomide within 12 weeks ptb (washout possible), - azathioprine, cyclophosphamide within 12 weeks ptb - Immunization with a live/attenuated vaccine within = 4 weeks ptb - Previous treatment with cell-depleting therapies, including investigational agents or approved therapies: anti-CD33, anti-CD52, anti-CD4, anti-CD5, anti- CD3 and anti-CD19 - Treatment with intravenous gamma globulin within 6 months of baseline - Treatment with plasmapheresis within 6 months of baseline - Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation Exclusions Related to General Safety - History of severe allergic or anaphylactic reactions to human, humanized, or murine antibodies - Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, psychiatric or GI disease - History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations - Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds) - Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening - Active TB requiring treatment within the previous 3 years; Patients should be screened for latent TB and, if positive, treated according to local practice guidelines prior to initiating TCZ treatment; Patients treated for TB with no recurrence within 3 years and patients treated for latent TB within 3 years are eligible. - Primary or secondary immunodeficiency (history of or currently active) - Evidence of malignant disease or malignancies diagnosed within the previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that have been excised and cured) - Females of childbearing potential who are not willing to use an effective method of contraception, such as condom, sterilization, or true abstinence throughout stu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Tocilizumab in patients with active FMF in a randomized, placebo controlled setting Efficacy: measured by Physician’s Global Assessment of disease activity (PGA) at week 16 Primary endpoint will be the number of patients achieving an adequate response to treatment at week 16, defined as: PGA = 2 + normalized ESR and/or CRP (the one that led to inclusion must be normalized) + normalized SAA;Secondary Objective: - To evaluate the safety of TCZ in subjects with FMF - To evaluate the proportion of patients achieving a Physician Global assessment of disease activity (PGA) = 2 (minimal or none) at week 16 - To evaluate the proportion of patients with the serological remission at week 16 + 28 (defined as CRP < 0.5 mg/dl) - To evaluate the proportion of patients with normalized SAA level at week 16 + 28 (defined as SAA < 10mg/l) - To evaluate the possibility of reducing intake of ibuprofene, diclofenac or paracetamol - To evaluate health related quality of live assessed by FFbH, FACIT Fatigue;Primary end point(s): Efficacy: measured by Physician’s Global Assessment of disease activity (PGA) at week 16 Primary endpoint will be the number of patients achieving an adequate response to treatment at week 16, defined as: PGA = 2 + normalized ESR and/or CRP (the one that led to inclusion must be normalized) + normalized SAA;Timepoint(s) of evaluation of this end point: at week 16 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate the safety of TCZ in subjects with FMF - To evaluate the proportion of patients achieving a Physician Global assessment of disease activity (PGA) = 2 (minimal or none) at week 16 - To evaluate the proportion of patients with the serological remission at week 16 + 28 (defined as CRP < 0.5 mg/dl) - To evaluate the proportion of patients with normalized SAA level at week 16 + 28 (defined as SAA < 10mg/l) - To evaluate the possibility of reducing intake of ibuprofene, diclofenac or paracetamol - To evaluate health related quality of live assessed by FFbH, FACIT Fatigue;Timepoint(s) of evaluation of this end point: disease activity (PGA) = 2 (minimal or none) at week 16 serological remission at week 16 + 28 proportion of patients with normalized SAA level at week 16 + 28 To evaluate the possibility of reducing intake of ibuprofene, diclofenac or paracetamol at week 16 and 28 To evaluate health related quality of live assessed by FFbH, FACIT Fatigue at week 16 and 28 | — |
Countries
Germany
Contacts
Public ContactDepartment of Internal Medicine II
University Hospital Tuebingen
Outcome results
None listed