Hereditary Periodic FeversPhase 3NCT02059291

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

A Phase 3 study testing Canakinumab in people with Hereditary Periodic Fevers, run by Novartis Pharmaceuticals at 65 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 more about this study

Who is it for?: Ages 1 month and older
Conditions the study is for: Hereditary Periodic Fevers
What is being tested?: Canakinumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 203 participants
Where: 65 sitesin 16 countries
Study dates: 27 Jun 2014to 4 Jul 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 month and older
All sexes
No healthy volunteers
Child, Adult, Older adult

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

Trial locations and contacts

65 sites in 16 countries.

Country

City, postcode or hospital

65 sites in 16 countries

Italy10 sites

Novartis Investigative Site
Brescia, BS, 25123
Novartis Investigative Site
Florence, FI, 50139
Novartis Investigative Site
Genova, GE, 16147
Novartis Investigative Site
Messina, ME, 98125
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Pavia, PV, 27100
Novartis Investigative Site
Roma, RM, 00165
Novartis Investigative Site
Roma, 00168
Novartis Investigative Site
Sciacca, AG, 92019
Novartis Investigative Site
Trieste, TS, 34137

Other trials in Italy

Germany9 sites

Novartis Investigative Site
Berlin, 10117
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Germering, 82110
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Hamburg, 22081
Novartis Investigative Site
München, 80337
Novartis Investigative Site
Saint Augustin, 53757
Novartis Investigative Site
Tübingen, 72076

Other trials in Germany

Spain6 sites

Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
El Palmar, Murcia, 30120
Novartis Investigative Site
Esplugues de Llobregat, Barcelona, 08950
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
Valencia, Valencia, 46026

Other trials in Spain

Belgium5 sites

Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Edegem, Antwerpen, 2650
Novartis Investigative Site
Hasselt, 3500
Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Liège, 4000

Other trials in Belgium

Israel5 sites

Novartis Investigative Site
Haifa, 3339419
Novartis Investigative Site
Haifa, 3525408
Novartis Investigative Site
Jerusalem, 9103102
Novartis Investigative Site
Petah Tikva, 49202
Novartis Investigative Site
Ramat Gan, 5266202

Other trials in Israel

Russia5 sites

Novartis Investigative Site
Moscow, 115522
Novartis Investigative Site
Moscow, 117198
Novartis Investigative Site
Moscow, 119991
Novartis Investigative Site
Rostov-on-Don, 344022
Novartis Investigative Site
Saint Petersburg, 194100

Other trials in Russia

France4 sites

Novartis Investigative Site
Bron, 69677
Novartis Investigative Site
Le Kremlin-Bicêtre, 94275
Novartis Investigative Site
Nîmes, 30029
Novartis Investigative Site
Paris, 75015

Other trials in France

Japan4 sites

Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Niigata, 951-8520
Novartis Investigative Site
Sakyo-ku, Kyoto, 606 8507
Novartis Investigative Site
Yokohama, Kanagawa, 236-0004

Other trials in Japan

United States3 sites

Novartis Investigative Site
Ann Arbor, Michigan, 48109
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Los Angeles, California, 90027

Other trials in United States

Turkey (Türkiye)3 sites

Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Istanbul, TUR, 34098
Novartis Investigative Site
Istanbul, 34093

Other trials in Turkey (Türkiye)

United Kingdom3 sites

Novartis Investigative Site
Leeds, LS9 7TF
Novartis Investigative Site
London, NW3 2QG
Novartis Investigative Site
London, WC1N 1EH

Other trials in United Kingdom

Canada2 sites

Novartis Investigative Site
Calgary, Alberta, T3B 6A8
Novartis Investigative Site
Vancouver, British Columbia, V6H 3V4

Other trials in Canada

Hungary2 sites

Novartis Investigative Site
Budapest, 1023
Novartis Investigative Site
Budapest, 1094

Other trials in Hungary

Netherlands2 sites

Novartis Investigative Site
Nijmegen, 6500 HB
Novartis Investigative Site
Utrecht, 3508 GA

Other trials in Netherlands

Ireland1 site

Novartis Investigative Site
Galway

Other trials in Ireland

Switzerland1 site

Novartis Investigative Site
Lausanne, 1011

Other trials in Switzerland

About this study

Official title: A Randomized, Double-blind, Placebo Controlled Study of Canakinumab in Patients With Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF), With Subsequent Randomized Withdrawal/Dosing Frequency Reduction and Open-label Long-term Treatment Epochs

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 :
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)
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: Hereditary Periodic Fevers
Being tested: Canakinumab, Placebo
Keywords: Canakinumab, interleukin-1, Hereditary Periodic Fevers, auto-inflammatory diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CanakinumabDrug
Also called ACZ885
Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.
PlaceboDrug
Matching placebo to canakinumab solution for subcutaneous injection

Study groups in NCT02059291
Study group	Role	What they receive
crFMF: 150 mg	Experimental	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. Receives: Drug: Canakinumab
crCMF: placebo	Placebo comparator	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. Receives: Drug: Placebo
HIDS/MKD: 150 mg	Experimental	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. Receives: Drug: Canakinumab
HIDS/MKD: placebo	Placebo comparator	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. Receives: Drug: Placebo
TRAPS: 150 mg	Experimental	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 Receives: Drug: Canakinumab
TRAPS: placebo	Placebo comparator	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. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 16 weeks

Secondary outcomes (4)

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.
Measured: 16 weeks
Percentage of Participants With the Serologic Remission
Serologic remission was defined as C-reactive protein <= 10 mg/L.
Measured: 16 weeks
Percentage of Participants With Normalized Serum Amyloid A (SAA) Level
Normalized SAA was defined as SAA <= 10 mg/L.
Measured: 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.
Measured: 40 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jun 20144 Jul 2017

First posted11 Feb 2014 (estimated)
Study start27 Jun 2014
Primary completion4 Jul 2017
Study completion4 Jul 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Hereditary Periodic FeversStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 203 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02059291
Sponsor's protocol ID: CACZ885N2301
Status last verified: Apr 2018
First submitted: 7 Feb 2014
Last updated: 17 May 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Gattorno M, Obici L, Penades IC, Kallinich T, Benseler S, Dekker E, Levy J, De Benedetti F, Lachmann H. Long-Term Efficacy and Safety of Canakinumab in Patients With Tumor Necrosis Factor Receptor-Associated Periodic Syndrome: Results From a Phase III Trial. Arthritis Rheumatol. 2024 Feb;76(2):304-312. doi: 10.1002/art.42695. Epub 2023 Dec 8.
PubMed 37668289
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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics
Familial Mediterranean Fever (FMF), Autoinflammation
RecruitingObservational study
Ilaris NIS in Korea
Hereditary Periodic Fever Syndromes, Cryopyrin-associated Periodic Syndromes (CAPS)
RecruitingObservational study
Evaluating the Genetics and Immunology of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis (PFAPA) Syndrome and Other Tonsil Disorders
Periodic Fever, Aphthous Stomatitis, Pharyngitis, And Cervical Adenitis (Pfapa), Obstructive Sleep Apnea
Not yet recruiting
Efficacy and Safety of Thalidomide for Pediatric PFAPA Syndrome
Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome

All Hereditary Periodic Fevers trials

Study at a glance

From the registry record, last updated by the sponsor on 17 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-blind, Placebo Controlled Study of Canakinumab in Patients With Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF), With Subsequent Randomized Withdrawal/Dosing Frequency Reduction and Open-label Long-term Treatment Epochs
ClinicalTrials.gov ID: NCT02059291
Acronym / sponsor ID: CACZ885N2301
Conditions: Hereditary Periodic Fevers
Keywords: Canakinumab, interleukin-1, Hereditary Periodic Fevers, auto-inflammatory diseases
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 203 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 27 Jun 2014 (actual)
Primary completion: 4 Jul 2017 (actual)
Study completion: 4 Jul 2017 (actual)
First posted: 11 Feb 2014 (estimated)
Results: Posted 17 Mar 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 :
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)
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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
crFMF: 150 mg	Experimental	Drug: CanakinumabDuring 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.
crCMF: placebo	Placebo comparator	Drug: PlaceboDuring 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.
HIDS/MKD: 150 mg	Experimental	Drug: CanakinumabDuring 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.
HIDS/MKD: placebo	Placebo comparator	Drug: PlaceboDuring 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.
TRAPS: 150 mg	Experimental	Drug: CanakinumabDuring 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
TRAPS: placebo	Placebo comparator	Drug: PlaceboDuring 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.

Who may qualify

Ages: 1 month and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CanakinumabAlso: ACZ885Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.	Drug	HIDS/MKD: 150 mg, TRAPS: 150 mg, crFMF: 150 mg
PlaceboMatching placebo to canakinumab solution for subcutaneous injection	Drug	HIDS/MKD: placebo, TRAPS: placebo, crCMF: placebo

Primary outcome

Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks)
Time frame: 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.

4 secondary outcomes

Percentage of Participants Who Achieve Physician's Global Assessment (PGA) < 2
Time frame: 16 weeks
Percentage of Participants With the Serologic Remission
Time frame: 16 weeks
Percentage of Participants With Normalized Serum Amyloid A (SAA) Level
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)
Time frame: 40 weeks

Results and safety

Results posted to the registry on 17 Mar 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Epoch 2: crFMF: 150 mg	31	31
Epoch 2: crCMF: Placebo	32	31
Epoch 2: HIDS/MKD: 150 mg	37	36
Epoch 2: HIDS/MKD: Placebo	35	33
Epoch 2: TRAPS: 150 mg	22	22
Epoch 2: TRAPS: Placebo	24	22
Epoch 2: Non-randomized Open Label Treatment - crFMF	2	2
Epoch 2: Non-randomized Open Label HIDS/MKD	2	1
Epoch 2 (Epoch 3) - Non-randomized Open Label TRAPS	18	16
Epoch 3: crFMF Re-randomized From Epoch 2 - 150 mg	0	0
Epoch 3: crFMF Re-randomized From Epoch 2 - Placebo	0	0
Epoch 3: HIDs/MKD Re-randomized From Epoch 2 - 150 mg	0	0
Epoch 3: HIDS/MKD Re-randomized From Epoch 2 - Placebo	0	0
Epoch 3: TRAPS Re-randomized From Epoch 2 - 150 mg	0	0
Epoch 3: TRAPS Re-randomized From Epoch 2 - Placebo	0	0
Epoch 3: crFMF, HIDS/MKD, TRAPS - Not Re-randomized	0	0
Epoch 4: crFMF - Open Label Cumulative Dose <2700 mg	0	0
Epoch 4: crFMF - Open Label Cumulative Dose 2700 mg - <5400 mg	0	0
Epoch 4: crFMF - Open Label Cumulative Dose >=5400 mg	0	0
Epoch 4: HIDS/MKD - Open Label Cumulative Dose <2700 mg	0	0
Epoch 4: HIDS/MKD - OL Cumulative Dose 2700 - <=5400 mg	0	0
Epoch 4: HIDS/MKD - Open Label Cumulative Dose >=5400 mg	0	0
Epoch 4: TRAPS - Open Label Cumulative Dose < 2700 mg	0	0
Epoch 4: TRAPS - Open Label Cumulative Dose 2700 - <5400 mg	0	0
Epoch 4: TRAPS - Open Label Cumulative Dose >=5400 mg	0	0

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

Time frame: 16 weeks. Number. Unit: Percentage of participants

Measure	Epoch 2: crFMF: 150 mg n = 31	Epoch 2: crCMF: Placebo n = 32	Epoch 2: HIDS/MKD: 150 mg n = 37	Epoch 2: HIDS/MKD: Placebo n = 35	Epoch 2: TRAPS: 150 mg n = 22	Epoch 2: TRAPS: Placebo n = 24
Value	61.29	6.25	35.14	5.71	45.45	8.33

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

Population analysed: The Full Analysis Set (FAS), which consisted of all randomized participants in the randomized treatment epoch who received at least one dose of study drug in Epoch 2, was analyzed.

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: up to week 112. Other adverse events reported at 5% frequency or more

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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37668289Gattorno M, Obici L, Penades IC, Kallinich T, Benseler S, Dekker E, Levy J, De Benedetti F, Lachmann H. Long-Term Efficacy and Safety of Canakinumab in Patients With Tumor Necrosis Factor Receptor-Associated Periodic Syndrome: Results From a Phase III Trial. Arthritis Rheumatol. 2024 Feb;76(2):304-312. doi: 10.1002/art.42695. Epub 2023 Dec 8.
Derived from this study: PubMed 34554243Jeyaratnam 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.
Derived from this study: PubMed 29768139De 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

65 sites in 16 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Canakinumab in people with Hereditary Periodic Fevers, run by Novartis Pharmaceuticals at 65 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in Italy, Germany, Spain, Belgium, Israel and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Resolution of Initial Flare and Absence of New Flares up to the End of the Randomized Treatment Epoch (16 Weeks) (time frame: 16 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02059291, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2018.