CompletedNCT02059291Updated May 17, 2018Results posted

Study of Efficacy and Safety of Canakinumab in Patients With Hereditary Periodic Fevers

A Phase 3 interventional study of Canakinumab and Placebo in Hereditary Periodic Fevers, sponsored by Novartis Pharmaceuticals. Completed at 65 sites in 16 countries. Open to participants aged 1 Month and older. Per ClinicalTrials.gov, last updated 2018-05-17.

Sponsored by Novartis Pharmaceuticals · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 203
Allocation: Randomized
Ages: 1 Month and older
Sex: All

Study summary

This study is to determine whether canakinumab is able to induce and maintain a clinically meaningful reduction of disease activity in participants with Hereditary Periodic Fevers (HPF) compared to placebo.

Read the detailed description

This study consists of 3 randomized cohorts (one per condition of colchicine resistant/intolerant Familial Mediterranean Fever (crFMF), Hyper Immunoglobulin D Syndrome (also known as mevalonate kinase deficiency (HIDS/MKD), and Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), and 4 study epochs:

Epoch 1: a screening epoch to assess participant's eligibility;
Epoch 2: a randomized treatment epoch of 16 weeks where participants are randomized to canakinumab 150 mg every 4 weeks (q4w) or to placebo to obtain efficacy and safety data in a double-blind placebo controlled parallel-arm setting. This epoch contained 2 possible escape options :
1. early blinded escape option for non responders from Day 8 to Day 28 with here an add-on dose of 150mg canakinumab followed by blinded uptitration at the next scheduled visit (Day 29)
2. late unblinded escape option for non responders from Day 29 to Day 112; with open-label uptitration
Epoch 3: a randomized withdrawal epoch of 24 weeks where canakinumab responders from the randomized treatment epoch were re-randomized to canakinumab 150mg q8w or placebo to assess the potential for canakinumab to maintain clinical efficacy at a reduced dosing frequency;
Epoch 4: an open-label treatment epoch of 72 weeks to collect long-term

Conditions studied

Hereditary Periodic Fevers

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Keywords

Canakinumab, interleukin-1, Hereditary Periodic Fevers, auto-inflammatory diseases

In context

Familial Mediterranean Fever

69 studies on the registry are indexed under Familial Mediterranean Fever; 27 are open to participants now.

This study's enrollment of 203 is above the median of 40 across 32 interventional studies indexed under Familial Mediterranean Fever.

Browse Familial Mediterranean Fever studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 1 Month and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria: - Patient's written informed consent (or parent's written informed consent in case of pediatric patient) at screening - Male and female patients at least 2 years of age at the time of the screening visit. Male and female patients >28 days but \<2 years eligible for open label treatment only. - Confirmed diagnosis and active flare at randomization - CRP >10mg/L at randomization

Exclusion Criteria: - Use of the following therapies (within varying protocol defined timeframes): Corticosteroids, anakinra, canakinumab, rilonacept, tocilizumab, TNF inhibitors, abatacept, tofacitinib, rituximab, leflunomide, thalidomide, cyclosporine, intravenous immunoglobulin, 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, any other investigational biologics - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in - situ cervical cancer), treated or untreated - Significant medical diseases, including but not limited to the following: a. History of organ transplantation b. Elevated liver enzymes ≥3x ULN d. Increase in total bilirubin e. Serious hepatic disorder (Child-Pugh scores B or C) f. Chronic Kidney Disease g. Thyroid disease h. Diagnosis of active peptic ulcer disease i. Coagulopathy j. Significant CNS effects including vertigo and dizziness - Any conditions or significant medical problems which immunecompromise the patient and/or places the patient at unacceptable risk for immunomodulatory therapy - Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 203 participants (actual)

Study arms

Experimental
crFMF: 150 mg
During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing \<= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
Drug: Canakinumab
Placebo comparator
crCMF: placebo
During epoch 2, participants received matching placebo to canakinumab 150 mg Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab. 150mg, participants were uptitrated to open-label canakinumab 300 mg.
Drug: Placebo
Experimental
HIDS/MKD: 150 mg
During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing \<= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration.
Drug: Canakinumab
Placebo comparator
HIDS/MKD: placebo
During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg.
Drug: Placebo
Experimental
TRAPS: 150 mg
During Epoch 2, participants received canakinumab 150mg (or 2mg/kg for participants weighing \<= 40kg) q4w for 16 weeks. If participants were eligible for blinded escape, they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between day 8 and day 28, and then received blinded uptitration to canakinumab 300 mg q4w from day 29 through day 112. If patients on the highest allowed canakinumab dose of 300 mg (or 4 mg/kg for patients weighing ≤ 40 kg) q4w and re-flared (PGA ≥ 2 and CRP ≥ 30 mg/L) were not eligible for further up-titration
Drug: Canakinumab
Placebo comparator
TRAPS: placebo
During epoch 2, participants received matching placebo to canakinumab 150 mg qw4. Participants who required blinded escape,they received a single add-on dose of canakinumab (150 mg or 2mg/kg for participants weighing \<= 40kg) between Day 8 and 28 and then received blinded one dose of placebo and one dose of canakinumab q4w from day 29 through day 112. If flare or re-flare still occurred after receipt of canakinumab 150mg, participants were uptitrated to open-label canakinumab 300 mg.
Drug: Placebo

Interventions

DrugCanakinumab
Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.
Also known as: ACZ885
DrugPlacebo
Matching placebo to canakinumab solution for subcutaneous injection

What researchers measure

Primary outcomes

Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)
Resolution of the initial disease flare is defined as: Physician's Global Assessment of Disease activity (PGA) \<2 and C-reactive protein (CRP) within normal range (\<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.
Time frame: 16 weeks

Secondary outcomes

Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2
The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.
Time frame: 16 weeks
Percentage of Participants With the Serologic Remission
Serologic remission was defined as C-reactive protein \<= 10 mg/L.
Time frame: 16 weeks
Percentage of Participants With Normalized Serum Amyloid A (SAA) Level
Normalized SAA was defined as SAA \<= 10 mg/L.
Time frame: 16 weeks
Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks)
A responder was defined as a participant who had no flare between week 16 and week 40.
Time frame: 40 weeks

Results

Posted Mar 17, 2017

Participant flow

This study consists of 4 study epochs. A total of 203 participants ((181randomized + 4 non-randomized open-label participants in Epoch 2) + (18 TRAPS rollover participants from ACZ885D2203 (NCT01242813) and ACZ885D2207M in Epoch 3)) have been enrolled into this study.

Epoch 2

Participant flow — Epoch 2
Milestone	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo	Epoch 2: Non-randomized Open Label Treatment - crFMF	Epoch 2: Non-randomized Open Label HIDS/MKD	Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS
Started	31	32	37	35	22	24	2	2	18
Completed	31	31	36	33	22	22	2	1	16
Not completed	0	1	1	2	0	2	0	1	2
Withdrew: Lack of efficacy	0	0	0	1	0	1	0	0	0
Withdrew: Adverse event	0	0	1	1	0	0	0	1	1
Withdrew: Withdrawal by subject	0	1	0	0	0	1	0	0	1

Epoch 3

Participant flow — Epoch 3
Milestone	Epoch 2: Non-randomized Open Label Treatment - crFMF	Epoch 2: Non-randomized Open Label HIDS/MKD	Epoch 3: crFMF Re-randomized From Epoch 2 - 150 mg	Epoch 3: crFMF Re-randomized From Epoch 2 - Placebo	Epoch 3: HIDs/MKD Re-randomized From Epoch 2 - 150 mg	Epoch 3: HIDS/MKD Re-randomized From Epoch 2 - Placebo	Epoch 3: TRAPS Re-randomized From Epoch 2 - 150 mg	Epoch 3: TRAPS Re-randomized From Epoch 2 - Placebo	Epoch 3: crFMF, HIDS/MKD, TRAPS - Not Re-randomized
Started	2	1	9	10	6	7	4	5	126
Completed	2	1	9	10	6	7	3	5	120
Not completed	0	0	0	0	0	0	1	0	6
Withdrew: Physician decision	0	0	0	0	0	0	1	0	1
Withdrew: Adverse event	0	0	0	0	0	0	0	0	1
Withdrew: Lack of efficacy	0	0	0	0	0	0	0	0	3
Withdrew: Withdrawal by subject	0	0	0	0	0	0	0	0	1

Epoch 4

Participant flow — Epoch 4
Milestone	Epoch 4: crFMF - Open Label Cumulative Dose <2700 mg	Epoch 4: crFMF - Open Label Cumulative Dose 2700 mg - <5400 mg	Epoch 4: crFMF - Open Label Cumulative Dose >=5400 mg	Epoch 4: HIDS/MKD - Open Label Cumulative Dose <2700 mg	Epoch 4: HIDS/MKD - OL Cumulative Dose 2700 - <=5400 mg	Epoch 4: HIDS/MKD - Open Label Cumulative Dose >=5400 mg	Epoch 4: TRAPS - Open Label Cumulative Dose < 2700 mg	Epoch 4: TRAPS - Open Label Cumulative Dose 2700 - <5400 mg
Started	43	14	2	18	34	14	31	22
Completed	41	14	2	18	33	14	30	21
Not completed	2	0	0	0	1	0	1	1
Withdrew: Adverse event	1	0	0	0	0	0	1	0
Withdrew: Pregnancy	1	0	0	0	0	0	0	0
Withdrew: Withdrawal by subject	0	0	0	0	1	0	0	0
Withdrew: Lack of efficacy	0	0	0	0	0	0	0	1

Outcome measures

PrimaryPercentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)

Resolution of the initial disease flare is defined as: Physician's Global Assessment of Disease activity (PGA) \<2 and C-reactive protein (CRP) within normal range (\<= 10 mg/L) or reduction by at least 70% from baseline. The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.

Time frame:: 16 weeks
Reported as:: Number · Percentage of participants

Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)
Percentage of participants	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo
Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)	61.29	6.25	35.14	5.71	45.45	8.33

Statistical analysis

Epoch 2: crFMF: 150 mg vs Epoch 2: crCMF: Placebo · Fisher's exact test · p = <0.0001
Epoch 2: HIDS/MKD: 150 mg vs Epoch 2: HIDS/MKD: Placebo · Fisher's exact test · p = 0.0020
Epoch 2: TRAPS: 150 mg vs Epoch 2: TRAPS: Placebo · Fisher's exact test · p = 0.0050

SecondaryPercentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2

The PGA was evaluated by the investigator based on a 5-point scale: 0 = None (no) disease associated with clinical signs and symptoms; 1 = minimal disease associated signs and symptoms; 2 = mild disease associated signs and symptoms; 3 = moderate disease associated signs and symptoms; and 5 = severe disease associated signs and symptoms.

Time frame:: 16 weeks
Reported as:: Number · Percentage of participants

Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2
Percentage of participants	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo
Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2	64.52	9.38	45.95	5.71	45.45	4.17

Statistical analysis

Epoch 2: crFMF: 150 mg vs Epoch 2: crCMF: Placebo · Regression, Logistic · p = <0.0001 · Odds ratio (or): 16.96 · 95% CI 4.15 to 69.21
Epoch 2: HIDS/MKD: 150 mg vs Epoch 2: HIDS/MKD: Placebo · Regression, Logistic · p = 0.0006 · Odds ratio (or): 13.63 · 95% CI 2.83 to 65.59
Epoch 2: TRAPS: 150 mg vs Epoch 2: TRAPS: Placebo · Regression, Logistic · p = 0.0028 · Odds ratio (or): 23.79 · 95% CI 2.52 to 224.86

SecondaryPercentage of Participants With the Serologic Remission

Serologic remission was defined as C-reactive protein \<= 10 mg/L.

Time frame:: 16 weeks
Reported as:: Number · Percentage of participants

Percentage of Participants With the Serologic Remission
Percentage of participants	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo
Percentage of Participants With the Serologic Remission	67.74	6.25	40.54	5.71	36.36	8.33

Statistical analysis

Epoch 2: crFMF: 150 mg vs Epoch 2: crCMF: Placebo · Regression, Logistic · p = <0.0001 · Odds ratio (or): 29.78 · 95% CI 5.86 to 151.31
Epoch 2: HIDS/MKD: 150 mg vs Epoch 2: HIDS/MKD: Placebo · Regression, Logistic · p = 0.0010 · Odds ratio (or): 12.71 · 95% CI 2.53 to 63.89
Epoch 2: TRAPS: 150 mg vs Epoch 2: TRAPS: Placebo · Regression, Logistic · p = 0.0149 · Odds ratio (or): 6.64 · 95% CI 1.20 to 36.57

SecondaryPercentage of Participants With Normalized Serum Amyloid A (SAA) Level

Normalized SAA was defined as SAA \<= 10 mg/L.

Time frame:: 16 weeks
Reported as:: Number · Percentage of participants

Percentage of Participants With Normalized Serum Amyloid A (SAA) Level
Percentage of participants	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo
Percentage of Participants With Normalized Serum Amyloid A (SAA) Level	25.81	0.00	13.51	2.86	27.27	0.00

Statistical analysis

Epoch 2: crFMF: 150 mg vs Epoch 2: crCMF: Placebo · Regression, Logistic · p = 0.0286 · Odds ratio (or): 17.46 · 95% CI 0.92 to 332.92
Epoch 2: HIDS/MKD: 150 mg vs Epoch 2: HIDS/MKD: Placebo · Regression, Logistic · p = 0.0778 · Odds ratio (or): 5.26 · 95% CI 0.53 to 51.97
Epoch 2: TRAPS: 150 mg vs Epoch 2: TRAPS: Placebo · Regression, Logistic · p = 0.0235 · Odds ratio (or): 16.69 · 95% CI 1.04 to 268.50

SecondaryPercentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks)

A responder was defined as a participant who had no flare between week 16 and week 40.

Time frame:: 40 weeks
Reported as:: Number · Percentage of participants

Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks)
Percentage of participants	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo
Percentage of Participants of Canakinumab Responders From Epoch 2 Who Maintained a Clinically Meaningful Response (Absence of New Flares) (40 Weeks)	77.8	30.0	50.0	14.3	75.0	40.0

Statistical analysis

Epoch 2: crFMF: 150 mg vs Epoch 2: crCMF: Placebo · Regression, Logistic · p = 0.0513 · Odds ratio (or): 8.17 · 95% CI 0.75 to 113.44
Epoch 2: HIDS/MKD: 150 mg vs Epoch 2: HIDS/MKD: Placebo · Regression, Logistic · p = 0.2168 · Odds ratio (or): 6.00 · 95% CI 0.27 to 366.24
Epoch 2: TRAPS: 150 mg vs Epoch 2: TRAPS: Placebo · Regression, Logistic · p = 0.3571 · Odds ratio (or): 4.50 · 95% CI 0.15 to 313.49

Adverse events

Collected over up to week 112. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Non-randomized Open Label crFMF, HIDS/MKD Patients	0/4 (0%)	3/4 (75%)	4/4 (100%)
Non-randomized Open Label TRAPS Patients	0/18 (0%)	1/18 (5.6%)	18/18 (100%)
Randomized ACZ and Placebo TRAPS Patients - Placebo Events	0/46 (0%)	1/46 (2.2%)	14/46 (30.4%)
Randomized ACZ and Placebo TRAPS Pts - No Medication Events	0/46 (0%)	0/46 (0%)	1/46 (2.2%)
Randomized ACZ and Placebo TRAPS Patients - ACZ Events	0/46 (0%)	8/46 (17.4%)	43/46 (93.5%)
Randomized ACZ and Placebo HIDS/MKD Pts - Placebo Events	0/72 (0%)	6/72 (8.3%)	25/72 (34.7%)
Randomized ACZ and Placebo HIDS/MKD Pts - No Medication Events	0/72 (0%)	1/72 (1.4%)	1/72 (1.4%)
Randomized ACZ and Placebo HIDS/MKD Patients - ACZ Events	0/72 (0%)	16/72 (22.2%)	68/72 (94.4%)
Randomized ACZ and Placebo crFMF Patients - Placebo Events	0/63 (0%)	5/63 (7.9%)	29/63 (46%)
Randomized ACZ and Placebo crFMF Pts - No Medication Events	0/63 (0%)	0/63 (0%)	2/63 (3.2%)
Randomized ACZ and Placebo crFMF Patients - ACZ Events	0/63 (0%)	16/63 (25.4%)	54/63 (85.7%)
Any ACZ TRAPS Patients - Placebo Events	0/61 (0%)	0/61 (0%)	4/61 (6.6%)
Any ACZ TRAPS Patients - no Medication Events	0/61 (0%)	0/61 (0%)	1/61 (1.6%)
Any ACZ TRAPS Patients - ACZ Events	0/61 (0%)	9/61 (14.8%)	61/61 (100%)
Any ACZ HIDS/MKD Patients - Placebo Events	0/71 (0%)	3/71 (4.2%)	7/71 (9.9%)
Any ACZ HIDS/MKD Patients - No Medication Events	0/71 (0%)	1/71 (1.4%)	1/71 (1.4%)
Any ACZ HIDS/MKD Patients - ACZ Events	0/71 (0%)	18/71 (25.4%)	70/71 (98.6%)
Any ACZ crFMF Patients - Placebo Events	0/61 (0%)	3/61 (4.9%)	10/61 (16.4%)
Any ACZ crFMF Patients - No Medication Events	0/61 (0%)	0/61 (0%)	2/61 (3.3%)
Any ACZ crFMF Patients - ACZ Events	0/61 (0%)	17/61 (27.9%)	56/61 (91.8%)

Most frequent serious events

Showing 10 of 74

Most frequent serious events
Event	Non-randomized Open Label crFMF, HIDS/MKD Patients	Non-randomized Open Label TRAPS Patients	Randomized ACZ and Placebo TRAPS Patients - Placebo Events	Randomized ACZ and Placebo TRAPS Pts - No Medication Events	Randomized ACZ and Placebo TRAPS Patients - ACZ Events	Randomized ACZ and Placebo HIDS/MKD Pts - Placebo Events	Randomized ACZ and Placebo HIDS/MKD Pts - No Medication Events	Randomized ACZ and Placebo HIDS/MKD Patients - ACZ Events	Randomized ACZ and Placebo crFMF Patients - Placebo Events	Randomized ACZ and Placebo crFMF Pts - No Medication Events	Randomized ACZ and Placebo crFMF Patients - ACZ Events	Any ACZ TRAPS Patients - Placebo Events	Any ACZ TRAPS Patients - no Medication Events	Any ACZ TRAPS Patients - ACZ Events	Any ACZ HIDS/MKD Patients - Placebo Events	Any ACZ HIDS/MKD Patients - No Medication Events	Any ACZ HIDS/MKD Patients - ACZ Events	Any ACZ crFMF Patients - Placebo Events	Any ACZ crFMF Patients - No Medication Events	Any ACZ crFMF Patients - ACZ Events
PancytopeniaBlood and lymphatic system disorders	1/4	0/18	0/46	0/46	0/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	0/61	0/71	0/71	1/71	0/61	0/61	0/61
Hyper IgD syndromeCongenital, familial and genetic disorders	1/4	0/18	0/46	0/46	0/46	1/72	0/72	3/72	0/63	0/63	0/63	0/61	0/61	0/61	1/71	0/71	4/71	0/61	0/61	0/61
Hepatic failureHepatobiliary disorders	1/4	0/18	0/46	0/46	0/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	0/61	0/71	0/71	1/71	0/61	0/61	0/61
LaryngitisInfections and infestations	1/4	0/18	0/46	0/46	0/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	0/61	0/71	0/71	1/71	0/61	0/61	0/61
Pyoderma gangrenosumSkin and subcutaneous tissue disorders	1/4	0/18	0/46	0/46	0/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	0/61	0/71	0/71	0/71	0/61	0/61	1/61
PyrexiaGeneral disorders	0/4	1/18	0/46	0/46	3/46	0/72	0/72	2/72	1/63	0/63	1/63	0/61	0/61	4/61	0/71	0/71	2/71	1/61	0/61	1/61
Tumour necrosis factor receptor-associated periodic syndromeCongenital, familial and genetic disorders	0/4	0/18	1/46	0/46	3/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	3/61	0/71	0/71	0/71	0/61	0/61	0/61
PneumoniaInfections and infestations	0/4	0/18	0/46	0/46	0/46	1/72	0/72	4/72	0/63	0/63	0/63	0/61	0/61	0/61	1/71	0/71	4/71	0/61	0/61	0/61
DiarrhoeaGastrointestinal disorders	0/4	1/18	0/46	0/46	1/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	2/61	0/71	0/71	0/71	0/61	0/61	0/61
HypercalcaemiaMetabolism and nutrition disorders	0/4	1/18	0/46	0/46	0/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	1/61	0/71	0/71	0/71	0/61	0/61	0/61

Most frequent other events

Showing 10 of 125

Most frequent other events
Event	Non-randomized Open Label crFMF, HIDS/MKD Patients	Non-randomized Open Label TRAPS Patients	Randomized ACZ and Placebo TRAPS Patients - Placebo Events	Randomized ACZ and Placebo TRAPS Pts - No Medication Events	Randomized ACZ and Placebo TRAPS Patients - ACZ Events	Randomized ACZ and Placebo HIDS/MKD Pts - Placebo Events	Randomized ACZ and Placebo HIDS/MKD Pts - No Medication Events	Randomized ACZ and Placebo HIDS/MKD Patients - ACZ Events	Randomized ACZ and Placebo crFMF Patients - Placebo Events	Randomized ACZ and Placebo crFMF Pts - No Medication Events	Randomized ACZ and Placebo crFMF Patients - ACZ Events	Any ACZ TRAPS Patients - Placebo Events	Any ACZ TRAPS Patients - no Medication Events	Any ACZ TRAPS Patients - ACZ Events	Any ACZ HIDS/MKD Patients - Placebo Events	Any ACZ HIDS/MKD Patients - No Medication Events	Any ACZ HIDS/MKD Patients - ACZ Events	Any ACZ crFMF Patients - Placebo Events	Any ACZ crFMF Patients - No Medication Events	Any ACZ crFMF Patients - ACZ Events
PyrexiaGeneral disorders	1/4	5/18	1/46	1/46	14/46	11/72	0/72	39/72	3/63	0/63	13/63	0/61	1/61	19/61	4/71	0/71	40/71	2/61	0/61	13/61
DiarrhoeaGastrointestinal disorders	2/4	4/18	1/46	1/46	8/46	2/72	0/72	22/72	1/63	0/63	12/63	0/61	1/61	12/61	0/71	0/71	23/71	0/61	0/61	13/61
BronchitisInfections and infestations	2/4	1/18	1/46	0/46	1/46	0/72	0/72	10/72	0/63	1/63	0/63	1/61	0/61	2/61	0/71	0/71	11/71	0/61	1/61	1/61
ConjunctivitisInfections and infestations	2/4	1/18	0/46	0/46	4/46	0/72	0/72	2/72	1/63	0/63	1/63	0/61	0/61	5/61	0/71	0/71	3/71	1/61	0/61	2/61
GastroenteritisInfections and infestations	2/4	1/18	0/46	0/46	5/46	0/72	1/72	10/72	1/63	0/63	8/63	0/61	0/61	6/61	0/71	1/71	11/71	1/61	0/61	9/61
Drug eruptionSkin and subcutaneous tissue disorders	2/4	0/18	0/46	0/46	0/46	0/72	0/72	0/72	0/63	0/63	0/63	0/61	0/61	0/61	0/71	0/71	0/71	0/61	0/61	2/61
HeadacheNervous system disorders	1/4	2/18	3/46	0/46	12/46	4/72	0/72	30/72	2/63	0/63	16/63	1/61	0/61	14/61	1/71	0/71	31/71	0/61	0/61	16/61
Abdominal painGastrointestinal disorders	0/4	4/18	2/46	0/46	14/46	3/72	0/72	25/72	4/63	0/63	16/63	1/61	0/61	18/61	1/71	0/71	25/71	1/61	0/61	16/61
Familial mediterranean feverCongenital, familial and genetic disorders	1/4	0/18	0/46	0/46	0/46	0/72	0/72	1/72	15/63	2/63	19/63	0/61	0/61	0/61	0/71	0/71	1/71	5/61	2/61	20/61
Upper respiratory tract infectionInfections and infestations	0/4	3/18	2/46	0/46	10/46	3/72	0/72	22/72	1/63	0/63	12/63	1/61	0/61	13/61	1/71	0/71	22/71	1/61	0/61	12/61

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo	Epoch 2: Non-randomized Open Label Treatment - crFMF	Epoch 2: Non-randomized Open Label HIDS/MKD	Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS	Total
crFMF cohort - randomized	18.0 ± 15.02	18.0 ± 13.38	NA ± NA	NA ± NA	NA ± NA	NA ± NA	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	18 ± 14.10
HIDS/MKD cohort - randomized	NA ± NA	NA ± NA	12.0 ± 8.49	9.0 ± 11.64	NA ± NA	NA ± NA	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	11.0 ± 10.08
TRAPS cohort - randomized	NA ± NA	NA ± NA	NA ± NA	NA ± NA	13.5 ± 19.22	16.5 ± 18.25	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	15.5 ± 18.55
crFMF - non-randomized	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	24.5 (20 to 29)	NA (NA to NA)	NA (NA to NA)	24.5 (20 to 29)
HIDS/MKD - non-randomized	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	1.0 (1 to 1)	NA (NA to NA)	1.0 (1 to 1)
roll-over TRAPS - non-randomized	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	NA (NA to NA)	42.5 (15 to 81)	42.5 (15 to 81)

Sex: Female, Male
Sex: Female, Male(Participants)	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo	Epoch 2: Non-randomized Open Label Treatment - crFMF	Epoch 2: Non-randomized Open Label HIDS/MKD	Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS	Total
Female	14	15	24	19	10	13	2	0	7	104
Male	17	17	13	16	12	11	0	2	11	99

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Epoch 2: crFMF: 150 mg	Epoch 2: crCMF: Placebo	Epoch 2: HIDS/MKD: 150 mg	Epoch 2: HIDS/MKD: Placebo	Epoch 2: TRAPS: 150 mg	Epoch 2: TRAPS: Placebo	Epoch 2: Non-randomized Open Label Treatment - crFMF	Epoch 2: Non-randomized Open Label HIDS/MKD	Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0
Asian	0	1	0	1	2	4	2	1	0	11
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0	0
White	27	27	34	31	20	18	0	1	16	174
More than one race	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	4	4	3	3	0	2	0	0	2	18

Study locations

65 sites

Novartis Investigative Site
Los Angeles, California 90027, United States
Novartis Investigative Site
Ann Arbor, Michigan 48109, United States
Novartis Investigative Site
Cleveland, Ohio 44195, United States
Novartis Investigative Site
Edegem, Antwerpen 2650, Belgium
Novartis Investigative Site
Bruxelles, 1200, Belgium
Novartis Investigative Site
Hasselt, 3500, Belgium
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Liege, 4000, Belgium
Novartis Investigative Site
Calgary, Alberta T3B 6A8, Canada
Novartis Investigative Site
Vancouver, British Columbia V6H 3V4, Canada
Novartis Investigative Site
Bron Cedex, 69677, France
Novartis Investigative Site
Le Kremlin Bicetre, 94275, France
Novartis Investigative Site
Nimes Cedex, 30029, France
Novartis Investigative Site
Paris, 75015, France
Novartis Investigative Site
Berlin, 10117, Germany
Novartis Investigative Site
Berlin, 13353, Germany
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Germering, 82110, Germany
Novartis Investigative Site
Hamburg, 20246, Germany
Novartis Investigative Site
Hamburg, 22081, Germany
Novartis Investigative Site
Muenchen, 80337, Germany
Novartis Investigative Site
Saint Augustin, 53757, Germany
Novartis Investigative Site
Tübingen, 72076, Germany
Novartis Investigative Site
Budapest, 1023, Hungary
Novartis Investigative Site
Budapest, 1094, Hungary
Novartis Investigative Site
Galway, Ireland
Novartis Investigative Site
Haifa, 3339419, Israel
Novartis Investigative Site
Haifa, 3525408, Israel
Novartis Investigative Site
Jerusalem, 9103102, Israel
Novartis Investigative Site
Petach-Tikva, 49202, Israel
Novartis Investigative Site
Ramat Gan, 5266202, Israel
Novartis Investigative Site
Sciacca, AG 92019, Italy
Novartis Investigative Site
Brescia, BS 25123, Italy
Novartis Investigative Site
Firenze, FI 50139, Italy
Novartis Investigative Site
Genova, GE 16147, Italy
Novartis Investigative Site
Messina, ME 98125, Italy
Novartis Investigative Site
Pavia, PV 27100, Italy
Novartis Investigative Site
Roma, RM 00165, Italy
Novartis Investigative Site
Trieste, TS 34137, Italy
Novartis Investigative Site
Napoli, 80131, Italy
Novartis Investigative Site
Roma, 00168, Italy
Novartis Investigative Site
Fukuoka city, Fukuoka 812-8582, Japan
Novartis Investigative Site
Yokohama-city, Kanagawa 236-0004, Japan
Novartis Investigative Site
Sakyo-ku, Kyoto 606 8507, Japan
Novartis Investigative Site
Niigata, 951-8520, Japan
Novartis Investigative Site
Nijmegen, 6500 HB, Netherlands
Novartis Investigative Site
Utrecht, 3508 GA, Netherlands
Novartis Investigative Site
Moscow, 115522, Russian Federation
Novartis Investigative Site
Moscow, 117198, Russian Federation
Novartis Investigative Site
Moscow, 119991, Russian Federation
Novartis Investigative Site
Rostov on Don, 344022, Russian Federation
Novartis Investigative Site
Saint-Petersburg, 194100, Russian Federation
Novartis Investigative Site
Esplugues de Llobregat, Barcelona 08950, Spain
Novartis Investigative Site
Barcelona, Catalunya 08035, Spain
Novartis Investigative Site
Valencia, Comunidad Valenciana 46026, Spain
Novartis Investigative Site
El Palmar, Murcia 30120, Spain
Novartis Investigative Site
Madrid, 28034, Spain
Novartis Investigative Site
Madrid, 28046, Spain
Novartis Investigative Site
Lausanne, 1011, Switzerland
Novartis Investigative Site
Istanbul, TUR 34098, Turkey
Novartis Investigative Site
Ankara, 06100, Turkey
Novartis Investigative Site
Istanbul, 34093, Turkey
Novartis Investigative Site
Leeds, LS9 7TF, United Kingdom
Novartis Investigative Site
London, NW3 2QG, United Kingdom
Novartis Investigative Site
London, WC1N 1EH, United Kingdom

References and documents

Publications

Jeyaratnam J, Simon A, Calvo I, Constantin T, Shcherbina A, Hofer M, Gattorno M, Martini A, Bader-Meunier B, Vastert B, Levy J, Dekker E, de Benedetti F, Frenkel J. Long-term efficacy and safety of canakinumab in patients with mevalonate kinase deficiency: results from the randomised Phase 3 CLUSTER trial. Rheumatology (Oxford). 2022 May 5;61(5):2088-2094. doi: 10.1093/rheumatology/keab696. PubMed 34554243 ↗
De Benedetti F, Gattorno M, Anton J, Ben-Chetrit E, Frenkel J, Hoffman HM, Kone-Paut I, Lachmann HJ, Ozen S, Simon A, Zeft A, Calvo Penades I, Moutschen M, Quartier P, Kasapcopur O, Shcherbina A, Hofer M, Hashkes PJ, Van der Hilst J, Hara R, Bujan-Rivas S, Constantin T, Gul A, Livneh A, Brogan P, Cattalini M, Obici L, Lheritier K, Speziale A, Junge G. Canakinumab for the Treatment of Autoinflammatory Recurrent Fever Syndromes. N Engl J Med. 2018 May 17;378(20):1908-1919. doi: 10.1056/NEJMoa1706314. PubMed 29768139 ↗

Study documents

Study protocol · Oct 22, 2014
Statistical analysis plan · Jan 10, 2017

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 17, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02059291
Lead sponsor: Novartis Pharmaceuticals
Responsible party: Sponsor
First posted: Feb 11, 2014
Start date: Jun 27, 2014
Primary completion: Jul 4, 2017
Completion: Jul 4, 2017
Results posted: Mar 17, 2017
Last update: May 17, 2018

Study contacts

Novartis Pharmaceuticals

study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee: No

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