A Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis or Hereditary Periodic Fevers Who Participated in the CACZ885G2301E1, CACZ885G2306 or CACZ885N2301 Studies

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02334748
• Collaborator: (none)
• Enrollment: 31
• Locations: 3
• Arm: 1
• Actual Duration (Months): 45.9
• Patients Per Site: 10.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The objective of this extension protocol is to collect safety data (serious and non-serious adverse events) and to provide continuous canakinumab to patients in France who completed study CACZ885G2301E1(NCT00891046), CACZ885G2306 (NCT02296424) or CACZ885N2301 (NCT02059291) until a decision regarding reimbursement in France is effective for canakinumab (Ilaris®) in these indications.

Condition or Disease	Intervention/Treatment	Phase
Systemic Juvenile Idiopathic Arthritis; Hereditary Periodic Fevers	Drug: canakinumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A French Open-label Extension Study of Canakinumab in Patients Who Participated in International Phase III Studies CACZ885G2301E1 or CACZ885G2306 in Systemic Juvenile Idiopathic Arthritis and CACZ885N2301 in Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF)
• Actual Study Start Date: Nov 3, 2014
• Actual Primary Completion Date: Aug 31, 2018
• Actual Study Completion Date: Aug 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: canakinumab Patients will continue the same dose as their last dose administered in the study CACZ885G2301E1, CACZ885N2301 or CACZ885G2306. For all indications, the maximum canakinumab dose is 4 mg/kg or 300 mg for patients ≥ 40 kg. Ilaris® dosage may be adjusted (or interrupted) according to the clinical response and to investigators judgment.	Drug: canakinumab; canakinumab

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events [every 4 weeks up to 1 year]

   The objective of this protocol was to collect additional safety data (serious and non serious AEs) and to provide continuous Ilaris® (canakinumab) treatment to patients in France who completed CACZ885G2301E1, CACZ885N2301 or CACZ885G2306 studies.

2. All-cause Mortality [uo to 1 year]

   Number of participants who died for any reason during the study

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

Criteria applicable for patients with Systemic Juvenil Idiopathic Arthritis SJIA):

Patients who have completed the international studies CACZ885G2301E1 or CACZ885G2306 without any significant safety issue according to Investigator's opinion.

Patients who have completed the international CACZ885G2306 study and who successfully withdrew canakinumab treatment per protocol but with a disease relapse after the end of study visit will be allowed to participate in CACZ885GFR01 study (whatever the time of relapse from the end of study visit), if the investigator states that there is an indication to resume canakinumab.

Patients who have participated in the international CACZ885G2306 study but could not be randomized and then have continued canakinumab in part I until the end of the study at a dose of 4 mg/kg every 4 weeks may be switched to CACZ885GFR01 study if the investigator thinks that, in the interest of the patient, there is an indication to taper off canakinumab dose after a prolonged remission.

Criteria applicable for patients with HPF (TRAPS, HIDS, crFMF):

Patients who have completed the international CACZ885N2301 study without any significant safety issue according to Investigator's opinion.

Criteria applicable for all patients:

Parent's or legal guardian's written informed consent and child's assent, if appropriate, or patient's written informed consent for patients ≥ 18 years of age must be obtained before any study related activity or assessment is performed.

Exclusion Criteria:

• History of recurring infections

• Hypersensitivity to the active substance or to any of the excipients

other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Bron Cedex		France	69677
2	Novartis Investigative Site	Le Kremlin Bicetre		France	94275
3	Novartis Investigative Site	Paris		France	75015

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Dec 15, 2017
• Statistical Analysis Plan - Aug 31, 2018

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02334748
• Other Study ID Numbers: CACZ885GFR01; 2014-002872-95
• First Posted: Jan 8, 2015
• Last Update Posted: May 19, 2020
• Last Verified: May 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Juvenile Rheumatoid arthritis (JRA) chronic; systemic inflammatory disorder; painful joints; inflammation of the synovial membrane; auto-immune rheumatoid disease; reactive rheumatoid arthritis; Systemic Juvenile Rheumatoid arthritis (SJRA); Hereditary Periodic Fevers; Hereditary periodic fever syndrome(HPFS); Familial Mediterranean fever syndrome(FMFS); Hyperimmunoglobulinemia D; Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS); Muckle-Wells syndrome (MWS); Familial cold auto inflammatory syndrome
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Familial Mediterranean Fever; Hereditary Autoinflammatory Diseases; Amyloidosis; Fever; Hyperthermia

Study Results

Participant Flow

Arm/Group Title	Canakinumab
Arm/Group Description	Patients continued same dose as their last dose administered in the study CACZ885G2301E1, CACZ885N2301 or CACZ885G2306. For all indications, the maximum canakinumab dose was 4 mg/kg or 300 mg for patients ≥ 40 kg. Ilaris® dosage may have been adjusted (or interrupted) according to the clinical response and to investigator's judgment.
Period Title: Overall Study
STARTED	31
COMPLETED	23
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Canakinumab
Arm/Group Description	Patients will continue the same dose as their last dose administered in the study CACZ885G2301E1, CACZ885N2301 or CACZ885G2306. For all indications, the maximum canakinumab dose is 4 mg/kg or 300 mg for patients ≥ 40 kg. Ilaris® dosage may be adjusted (or interrupted) according to the clinical response and to investigators judgment.
Overall Participants	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.7 (4.07)
Sex: Female, Male (Count of Participants)
Female	17 54.8%
Male	14 45.2%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	29 93.5%
Other	2 6.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events
Description	The objective of this protocol was to collect additional safety data (serious and non serious AEs) and to provide continuous Ilaris® (canakinumab) treatment to patients in France who completed CACZ885G2301E1, CACZ885N2301 or CACZ885G2306 studies.
Time Frame	every 4 weeks up to 1 year

Outcome Measure Data

Analysis Population Description

Safety set: Safety set consisted of all patients who received at least one dose of study drug and had at least one post-treatment safety assessment in the study.

Arm/Group Title	Canakinumab
Arm/Group Description	Patients continued same dose as their last dose administered in the study CACZ885G2301E1, CACZ885N2301 or CACZ885G2306. For all indications, the maximum canakinumab dose is 4 mg/kg or 300 mg for patients ≥ 40 kg. Ilaris® dosage may have been adjusted (or interrupted) according to the clinical response and to investigators judgment.
Measure Participants	31
Serious adverse events	7 22.6%
Treatment emergent adverse events	29 93.5%

2. Primary Outcome

Title	All-cause Mortality
Description	Number of participants who died for any reason during the study
Time Frame	uo to 1 year

Outcome Measure Data

Analysis Population Description

Safety set

Arm/Group Title	Canakinumab
Arm/Group Description	Patients continued same dose as their last dose administered in the study CACZ885G2301E1, CACZ885N2301 or CACZ885G2306. For all indications, the maximum canakinumab dose is 4 mg/kg or 300 mg for patients ≥ 40 kg. Ilaris® dosage may have been adjusted (or interrupted) according to the clinical response and to investigators judgment.
Measure Participants	31
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for approximately 12 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of 1 year
Adverse Event Reporting Description	All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 1 year
Arm/Group Title	Canakinumab (ACZ885)
Arm/Group Description	Patients continued the same dose as their last dose administered in the study CACZ885G2301E1, CACZ885N2301 or CACZ885G2306. For all indications, the maximum canakinumab dose is 4 mg/kg or 300 mg for patients ≥ 40 kg. Ilaris® dosage may have been adjusted (or interrupted) according to the clinical response and to investigators judgment.
All Cause Mortality
	Canakinumab (ACZ885)
	Affected / at Risk (%)	# Events
Total	0/31 (0%)
Serious Adverse Events
	Canakinumab (ACZ885)
	Affected / at Risk (%)	# Events
Total	7/31 (22.6%)
Blood and lymphatic system disorders
Histiocytosis haematophagic	1/31 (3.2%)
Gastrointestinal disorders
Abdominal pain	2/31 (6.5%)
Infections and infestations
Epstein-Barr virus infection	1/31 (3.2%)
Salmonellosis	1/31 (3.2%)
Injury, poisoning and procedural complications
Intentional overdose	1/31 (3.2%)
Scar	1/31 (3.2%)
Musculoskeletal and connective tissue disorders
Arthritis	2/31 (6.5%)
Bone disorder	1/31 (3.2%)
Psychiatric disorders
Hallucination, auditory	1/31 (3.2%)
Suicide attempt	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Canakinumab (ACZ885)
	Affected / at Risk (%)	# Events
Total	28/31 (90.3%)
Blood and lymphatic system disorders
Lymphadenopathy	3/31 (9.7%)
Gastrointestinal disorders
Abdominal pain	6/31 (19.4%)
Abdominal pain upper	2/31 (6.5%)
Diarrhoea	4/31 (12.9%)
Mouth ulceration	2/31 (6.5%)
Nausea	2/31 (6.5%)
Toothache	2/31 (6.5%)
General disorders
Asthenia	3/31 (9.7%)
Pyrexia	7/31 (22.6%)
Infections and infestations
Bronchitis	3/31 (9.7%)
Conjunctivitis	4/31 (12.9%)
Gastroenteritis	7/31 (22.6%)
Influenza	4/31 (12.9%)
Labyrinthitis	2/31 (6.5%)
Molluscum contagiosum	2/31 (6.5%)
Nasopharyngitis	11/31 (35.5%)
Onychomycosis	2/31 (6.5%)
Oral herpes	2/31 (6.5%)
Paronychia	4/31 (12.9%)
Pharyngitis	4/31 (12.9%)
Rhinitis	4/31 (12.9%)
Sinusitis	2/31 (6.5%)
Tonsillitis	4/31 (12.9%)
Tracheitis	4/31 (12.9%)
Viral infection	4/31 (12.9%)
Injury, poisoning and procedural complications
Ligament sprain	2/31 (6.5%)
Limb injury	2/31 (6.5%)
Metabolism and nutrition disorders
Iron deficiency	2/31 (6.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/31 (29%)
Arthritis	2/31 (6.5%)
Back pain	3/31 (9.7%)
Juvenile idiopathic arthritis	3/31 (9.7%)
Musculoskeletal pain	2/31 (6.5%)
Myalgia	2/31 (6.5%)
Neck pain	2/31 (6.5%)
Pain in extremity	4/31 (12.9%)
Pain in jaw	2/31 (6.5%)
Scoliosis	2/31 (6.5%)
Tendon pain	2/31 (6.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	2/31 (6.5%)
Nervous system disorders
Headache	4/31 (12.9%)
Respiratory, thoracic and mediastinal disorders
Cough	3/31 (9.7%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	2/31 (6.5%)
Dry skin	2/31 (6.5%)
Eczema	4/31 (12.9%)
Rash	2/31 (6.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.