Evaluate the Safety and Efficacy of Canakinumab in Pediatric Patients With Colchicine Intolerant or Colchicine Resistant Familial Mediterranean Fever (FMF) (CONTROL FMF)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01148797
First received: June 21, 2010
Last updated: March 5, 2014
Last verified: March 2014
  Purpose

A study designed to evaluate the role of treatment with a biological agent - Canakinumab in pediatric (age 4-20) Familial Mediterranean Fever (FMF) patients that are intolerant or resistant for colchicine treatment.

The study hypothesis is that Canakinumab will reduce attack frequency and severity.


Condition Intervention Phase
Colchicine Resistant/Intolerant Familial Mediterranean Fever
Drug: Canakinumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A 6 Month Phase 2, Multi-Center, Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Treatment With Canakinumab in Pediatric Patients With Colchicine Intolerant or Colchicine Resistant Familial Mediterranean Fever

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • To measure the effect of canakinumab on the frequency of FMF attacks, defined as percentage of subjects with at least 50% reduction in the attack frequency during a 3 month treatment period [ Time Frame: 0-3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the effect of canakinumab with regard to percentage of subjects with no attacks during the 3 months treatment period [ Time Frame: 0-3 months ] [ Designated as safety issue: No ]
  • To evaluate the safety and tolerability of canakinumab by monitoring adverse events (AEs) and subject discontinuations due to an AE [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • To assess the change in frequency of FMF attacks during the treatment period [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: December 2010
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Canakinumab Drug: Canakinumab

  Eligibility

Ages Eligible for Study:   4 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female subjects between 4 and 20 years of age with active type 1 FMF disease (according to Tel-Hashomer Long criteria for diagnosis of FMF) and genetic confirmation of diagnosis (for the study - genetic confirmation is defined as either homozygous or compound heterozygous).
  2. Subjects must have type 1 disease characterized by recurrent and short episodes of inflammation and serositis, with an average of at least 3 well documented acute FMF attacks during the previous 3 months that are confirmed by the treating physician, lasting less then a week, and a minimum 14 day- attack free interval between attacks.
  3. Subjects must have received an adequate trial of colchicine, defined as treatment of at least 1-2 mg/d (based on subjects age) for at least 3 months, or an inability to tolerate colchicine due to adverse effects in a dose that controls acute attacks in the frequency of less than one attack per month.
  4. Subjects treated with anti-IL-1 therapies must complete washout and have experienced at least 2 attacks since (e.g. Anakinra: 3 day washout; Rilonacept: 4 week washout)
  5. Subjects 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 - a full list of washout periods for current treatments will be supplied
  6. If subject is a female of childbearing potential, she must agree to use adequate contraception (adequate contraception can include abstinence) for the duration of the trial and 3 months after, and must have a negative serum or urine pregnancy test prior to administration of each dose of study medication.
  7. Subject's parent or legal guardian has provided written informed consent prior to screening for this study, or if subject is older than 18 years has provided informed consent him/herself.

Exclusion Criteria:

  1. Patients with end-organ dysfunction due to amyloidosis (e.g. existing biopsy proven amyloidosis or proteinuria > 0.5 gram per day)
  2. Subjects taking oral or IV steroids within 1 month prior to baseline. Subjects taking steroids for reasons other than FMF - may be enrolled into the study based on discussion with the investigator and sponsor.
  3. Presence or history of any other inflammatory rheumatic disease
  4. The subject has active non-infective GI disease (e.g., inflammatory bowel disease), a chronic or acute renal or hepatic disorder, or a significant coagulation defect.
  5. The subject has an AST (SGOT), ALT (SGPT) or BUN >2 x ULN or creatinine >1.5 mg/dL, and any other laboratory abnormality considered by the examining physician to be clinically significant within 28 days before the Baseline visit.
  6. 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) or via Chest x-ray.
  7. The subject has positive human immunodeficiency virus (HIV) status or current (acute or chronic) hepatitis B or C
  8. Subjects who are pregnant or lactating
  9. 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
  10. Malignancy, except for successfully excised squamous or basal cell carcinoma of the skin
  11. The subject has received any investigational medication within 30 days before the first dose of study medication or is scheduled to receive an investigational drug, other than study medications described in this protocol, during the course of the study.
  12. The subject has received a live virus vaccine within 3 months prior to the baseline visit.
  13. Any concurrent medical condition which would, in the investigator's opinion, compromise the subject's ability to tolerate the study drug or would make the subject unable to follow with the protocol.
  14. History of/or current psychiatric illness that would interfere with ability to comply with protocol requirements or provide informed consent.
  15. Subject has a history of alcohol or drug abuse within the past 6 months that would interfere with ability to comply with protocol requirements.

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01148797

Locations
Israel
Rambam Health Care Campus
Haifa, Israel
Shaare Zedek Medical Center
Jerusalem, Israel
Meir Medical Center Kfar Saba
Kfar Saba, Israel
Rabin Medical Center
Petach Tikva, Israel
The Chaim Sheba Medical Center
Ramat Gan, Israel
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Chair: Eliad Ben Dayan Novartis Pharmaceuticals
  More Information

Publications:

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01148797     History of Changes
Other Study ID Numbers: CACZ885D2204
Study First Received: June 21, 2010
Last Updated: March 5, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Novartis:
FMF, Colchicine resistant
Colchicine intolerant
Flare rate
Canakinumab

Additional relevant MeSH terms:
Fever
Brucellosis
Familial Mediterranean Fever
Hereditary Autoinflammatory Diseases
Body Temperature Changes
Signs and Symptoms
Gram-Negative Bacterial Infections
Bacterial Infections
Genetic Diseases, Inborn
Skin Diseases, Genetic
Skin Diseases
Colchicine
Antibodies, Monoclonal
Gout Suppressants
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014