Efficacy and Safety of Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever

An Open-label, Exploratory Study to Establish the Safety and Efficacy of 3 Months Treatment With Canakinumab in Patients With Colchicine Resistant Familial Mediterranean Fever

Establish the safety and efficacy of 3 months treatment with canakinumab in patients with colchicine resistant Familial Mediterranean Fever.

Study Overview

• Status: Completed
• Conditions: Familial Mediterranean Fever
• Intervention / Treatment: Drug: Canakinumab

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• Turkey
  • Istanbul, Turkey
    • Istanbul Medical Faculty, Dept of Rheumatology, Capa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 75 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients between 12 and 75 years of age with active type 1 FMF disease (according to Tel-Hashomer criteria for diagnosis of FMF) despite colchicine therapy (1.5 to 2.0 mg/day).
• Patients who are intolerant to effective doses of colchicine (1.5 to 2 mg/day)
• Patients with demonstrated minimum 1 typical acute attack per month and genetic confirmation of diagnosis (with at least one of the known MEFV gene exon 10 mutations). Patients with manifested amyloidosis are excluded.
• Patients must have a historical data showing a frequency of at least 1 attack/month within the last 3 months before they can be enter the run-in period.
• Patients must have type 1 disease characterized by recurrent and short episodes of inflammation and serositis with an average of at least 1 documented acute FMF attack per month during the previous 6 months and lasting approximately 12 to 72 hours.
• Patients treated with IL-1 therapies must complete washout and have experienced at least 2 attacks since (e.g. Anakinra: 3 day washout; Rilonacept: 3 week washout)
• Patients treated with anti-TNF drugs must undergo appropriate washout. Prior to randomization, use of Etanercept must be discontinued for 4 weeks or use of Adalimumab or Infliximab must be discontinued for 8 weeks.
• Female subjects of childbearing potential must be using two acceptable methods of contraception
• Patients treated with Interferon therapies must complete 1 month washout period.

Exclusion Criteria:

• Patients with end-organ dysfunction due to amyloidosis (e.g. existing biopsy proven amyloidosis or proteinuria > 0.5 gram per day)
• Patients taking steroids within 1 month prior to baseline
• Presence or history of any other inflammatory rheumatic disease
• Positive PPD test (according to local guidance) where a latent or active TB infection cannot be excluded via Quantiferon (T-Spot or radiographic imaging if needed).
• Patients who are pregnant or lactating
• Presence of any active or chronic infection or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 30 days or oral antibiotics within 14 days prior to screening
• History or a malignancy within the last 5 years, except for successfully excised squamous or basal cell carcinoma of the skin

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Canakinumab	Drug: Canakinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To measure the effect of canakinumab on the frequency of FMF attacks defined as percentage of patients with at least 50% reduction in the attack frequency during 3 month treatment period.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the effect of canakinumab with regard to percentage of patients with no attacks in month 3.	12 weeks
To find the optimal dose of canakinumab for FMF in this population	12 weeks
To assess changes in the severity (acute phase response and VAS evaluation of attack severity by patient) and duration of acute attacks during the treatment period	12 weeks
To assess PK/PD properties of canakinumab by measuring canakinumab and IL-1beta levels before dosing
To evaluate the safety and tolerability of canakinumab by monitoring adverse events and patient discontinuations due to AE

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Gul A, Ozdogan H, Erer B, Ugurlu S, Kasapcopur O, Davis N, Sevgi S. Efficacy and safety of canakinumab in adolescents and adults with colchicine-resistant familial Mediterranean fever. Arthritis Res Ther. 2015 Sep 4;17(1):243. doi: 10.1186/s13075-015-0765-4.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: March 16, 2010
• First Submitted That Met QC Criteria: March 16, 2010
• First Posted (ESTIMATE): March 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 1, 2012
• Last Update Submitted That Met QC Criteria: April 27, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: colchicine resistance; canakinumab; Familial Mediterranean Fever
• Additional Relevant MeSH Terms: Skin Diseases; Infections; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Skin Diseases, Genetic; Body Temperature Changes; Fever; Brucellosis; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases
• Other Study ID Numbers: CACZ885DTR01