Tocilizumab for the Treatment of Familial Mediterranean Fever

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03446209
• Date of registration: 11/12/2017
• Prospective Registration: Yes
• Primary sponsor: University Hospital Tuebingen
• Public title: Tocilizumab for the Treatment of Familial Mediterranean Fever
• Scientific title: Tocilizumab for the Treatment of Familial Mediterranean Fever - A Randomized, Doubleblind, Phase II Proof of Concept Study
• Date of first enrolment: April 23, 2018
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03446209
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Germany

Key inclusion & exclusion criteria

Inclusion Criteria:

- Age = 18 years and written informed consent

- FMF according to the Tel Hashomer Criteria; with at least one heterozygous or
homozygous mutation of the MEFV gene

- Inadequate response or intolerance to colchicine (inadequate response/intolerance:

disease activity despite colchicine with at least 2 x 0.5 mg/day 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 > 0.5 mg/dl and/or ESR > 20mm/h and/or SAA > 10mg/dl

- PGA >2

- Understand and voluntarily sign an informed consent document prior to any study
related assessments/procedures.

- Ability to adhere to the study visit schedule and other protocol requirements.

- Females of childbearing potential (FCBP*) must agree to utilize two reliable forms of
contraception simultaneously from heterosexual contact for at least 28 days before
starting study drug, while participating in the study (including dose interruptions),
and for 6 months after study treatment discontinuation and must agree to regular
pregnancy testing during this timeframe to abstain from breastfeeding during study
participation and 6 months after study drug discontinuation.

- Males must agree to use a latex condom during any sexual contact with FCBP while
participating in the study and for 6 months following discontinuation from this study,
even if he has undergone a successful vasectomy to refrain from donating semen or
sperm while on Tocilizumab/Placebo and 6 months after discontinuation from this study
treatment.

- All subjects must agree to refrain from donating blood while on study drug and 6
months after discontinuation from this study treatment.

- All subjects must agree not to share medication.

A female of childbearing potential is a sexually mature woman who: 1) has not undergone a
hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at
least 24 consecutive months (i.e., who has had menses at any time in the preceding 24
consecutive months).

Exclusion Criteria:

Subjects presenting with any of the following criteria will not be included in the trial:

- Patient participating simultaneously in other clinical interventional trials

- Major surgery within 8 weeks prior to screening or planned major surgery within 12
months after randomization

- Transplanted organs (except corneal transplant performed more than 3 months prior to
screening)

Exclusions Related to Prior or Concomitant Therapy

- Previous treatment with TCZ

- Treatment with glucocorticosteroids >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 or colchicine,
which can be used at a stable dose throughout the study and/or for treatment of FMF
attacks to the maximum allowed daily dose (paracetamol: 4000mg/day, ibuprofene:
maximum 2400mg/day, diclofenac maximum 150mg/day; colchicine 12mg/day) .

- 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
gastrointestinal (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)

- FCBP who are not willing to use an effective method of contraception, such as condom,
sterilization during the study and for a minimum of 6 months after study drug therapy
and breast-feeding females

- Pregnant women

- Males of reproductive potential who are not willing to use an effective method of
contraception, such as condom, sterilization, or true abstinence throughout study and
for a minimum of 6 months after study drug therapy

- History of alcohol, drug, or chemical abuse within 1 year prior to screening

L


Age minimum: 18 Years
Age maximum: 64 Years
Gender: All

Health Condition(s) or Problem(s) studied

Familial Mediterranean Fever

Intervention(s)

Drug: 0.9% physiological saline

Drug: Tocilizumab Infusion RoAcemtra (EU)

Primary Outcome(s)

Efficacy: measured change of Physician's Global Assessment of disease activity (PGA) [Time Frame: at week -4,0,4,8,12,16,20,24,28,32]

Secondary Outcome(s)

Incidence of Treatment-Emergent Adverse Events-Determination of Erytthro Sedimentation Rate (ESR) [Time Frame: at week -4,0,4,8,12,16,20,24,28,32]

SAA level [Time Frame: at week 16 + 28]

serological remission [Time Frame: at week 16, 28]

Secondary ID(s)

TOFFIFE 1.1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors