Tocilizumab for the Treatment of Familial Mediterranean Fever

NCT03446209 | Completed Phase 2

• 1 other identifier: TOFFIFE 1.1
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

Adult patients with Familial Mediterranean Fever, who have active disease

Conditions

Familial Mediterranean Fever

Outcome Measures

Primary Outcomes (1)

• Efficacy: measured change of Physician's Global Assessment of disease activity (PGA)

  Efficacy: measured by Physician's Global Assessment of disease activity (PGA) will be assessed at every visit The PGA will be based on a 5 point-scale (from 0 to 4): 0=none (no) disease associated clinical signs and symptoms\* 1. minimal disease associated clinical signs and symptoms\* 2. mild disease associated clinical signs and symptoms\* 3. moderate disease associated clinical signs and symptoms\* 4. severe disease associated clinical signs and symptoms\* \*sign and symptoms for evaluation of PGA: chest pain, abdominal pain, arthralgia, arthritis, skin rash, fever (body temperature ≥ 38.0°C). Patient are asked to fill out a patient's diary to help the physician to judge the PGA primary endpoint will be the number of patients achieving an adequate response to treatment at week 16, defined as: PGA ≤ 2 + normalized ESR or CRP (the one that led to inclusion must be normalized) + normalized SAA

  at week -4,0,4,8,12,16,20,24,28,32

Secondary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events-Determination of Erytthro Sedimentation Rate (ESR)

  at week -4,0,4,8,12,16,20,24,28,32

• serological remission

  at week 16, 28

• SAA level

  at week 16 + 28

Other Outcomes (9)

• Incidence of Treatment-Emergent Adverse Events -Determination of the C-reactive protein

  at week -4,0,4,8,12,16,20,24,28,32

• Incidence of Treatment-Emergent Adverse Events -Determination of the blood cell count

  at week -4,0,4,8,12,16,20,24,28,32

• Incidence of Treatment-Emergent Adverse Events -Determination of serum parameters (Creatinine)

  at week -4,0,4,8,12,16,20,24,28,32

Study Arms (2)

Tocilizumab

EXPERIMENTAL

Tocilizumab Infusion RoAcemtra (EU) or Actemra (Rest of the world)

Drug: Tocilizumab Infusion RoAcemtra (EU)

Placebo

PLACEBO COMPARATOR

0,9% physiological Saline

Drug: Tocilizumab Infusion RoAcemtra (EU); Drug: 0.9% physiological saline

Interventions

Tocilizumab Infusion RoAcemtra (EU) DRUG

Experimental arm's patients will obtain TCZ intravenously once every 4 weeks for 28 weeks

Also known as: Actemra

Placebo; Tocilizumab

0.9% physiological saline DRUG

Experimental arm's patients will obtain saline intravenously once every 4 weeks for 16 weeks. If necessary, patients will get "rescue medication" after week 16 to week 28.

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (3)

Universitätsklinikum Köln, Klinik I für Innere Medizin

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Charité Universitätsmedizin Berlin, Klinik für Rheumatologie und Klinische Immunologie, Abteilung -Neue Therapien & Studien

Berlin, 10117, Germany

Location

University Hospital Tuebingen; Department of oncology, hematology, rheumatology, immunology and pulmology

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Familial Mediterranean Fever

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Investigator and patient will be masked. There' ll be one qualified person in each center who s not going to be masked to prepare study treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multi-center, phase II, randomized, placebo-controlled, double blind proof of concept trial

Study Record Dates

• First Submitted: December 11, 2017
• First Posted: February 26, 2018
• Study Start: April 23, 2018
• Primary Completion: October 30, 2020
• Study Completion: October 30, 2020
• Last Updated: November 18, 2020

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)