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

NCT02059291 | Completed Phase 3 Results

• 1 other identifier: CACZ885N2301
• Study Type: interventional
• Target: 203
• Locations: 16 countries
• Sites: 65

Brief 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.

Conditions

Hereditary Periodic Fevers

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  16 weeks

Secondary Outcomes (4)

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

  16 weeks

• Percentage of Participants With the Serologic Remission

  16 weeks

• Percentage of Participants With Normalized Serum Amyloid A (SAA) Level

  16 weeks

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

  40 weeks

Study Arms (6)

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.

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.

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.

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.

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

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.

Drug: Placebo

Interventions

Canakinumab DRUG

Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.

Also known as: ACZ885

HIDS/MKD: 150 mg; TRAPS: 150 mg; crFMF: 150 mg

Placebo DRUG

Matching placebo to canakinumab solution for subcutaneous injection

HIDS/MKD: placebo; TRAPS: placebo; crCMF: placebo

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (65)

Novartis Investigative Site

Los Angeles, California, 90027, United States

Location

Novartis Investigative Site

Ann Arbor, Michigan, 48109, United States

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Novartis Investigative Site

Cleveland, Ohio, 44195, United States

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Novartis Investigative Site

Edegem, Antwerpen, 2650, Belgium

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Brussels, 1200, Belgium

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Novartis Investigative Site

Hasselt, 3500, Belgium

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Leuven, 3000, Belgium

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Novartis Investigative Site

Liège, 4000, Belgium

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Novartis Investigative Site

Calgary, Alberta, T3B 6A8, Canada

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Novartis Investigative Site

Vancouver, British Columbia, V6H 3V4, Canada

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Novartis Investigative Site

Bron, 69677, France

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Novartis Investigative Site

Le Kremlin-Bicêtre, 94275, France

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Novartis Investigative Site

Nîmes, 30029, France

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Paris, 75015, France

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Novartis Investigative Site

Berlin, 10117, Germany

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Berlin, 13353, Germany

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Novartis Investigative Site

Essen, 45147, Germany

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Germering, 82110, Germany

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Hamburg, 20246, Germany

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Hamburg, 22081, Germany

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Novartis Investigative Site

München, 80337, Germany

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Saint Augustin, 53757, Germany

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Tübingen, 72076, Germany

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Novartis Investigative Site

Budapest, 1023, Hungary

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Budapest, 1094, Hungary

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Novartis Investigative Site

Galway, Ireland

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Novartis Investigative Site

Haifa, 3339419, Israel

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Haifa, 3525408, Israel

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Novartis Investigative Site

Jerusalem, 9103102, Israel

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Novartis Investigative Site

Petah Tikva, 49202, Israel

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Novartis Investigative Site

Ramat Gan, 5266202, Israel

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Novartis Investigative Site

Sciacca, AG, 92019, Italy

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Novartis Investigative Site

Brescia, BS, 25123, Italy

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Novartis Investigative Site

Florence, FI, 50139, Italy

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Novartis Investigative Site

Genova, GE, 16147, Italy

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Novartis Investigative Site

Messina, ME, 98125, Italy

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Novartis Investigative Site

Pavia, PV, 27100, Italy

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Novartis Investigative Site

Roma, RM, 00165, Italy

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Novartis Investigative Site

Trieste, TS, 34137, Italy

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Novartis Investigative Site

Napoli, 80131, Italy

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Novartis Investigative Site

Roma, 00168, Italy

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Novartis Investigative Site

Fukuoka, Fukuoka, 812-8582, Japan

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Yokohama, Kanagawa, 236-0004, Japan

Location

Novartis Investigative Site

Sakyo-ku, Kyoto, 606 8507, Japan

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Novartis Investigative Site

Niigata, 951-8520, Japan

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Novartis Investigative Site

Nijmegen, 6500 HB, Netherlands

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Utrecht, 3508 GA, Netherlands

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Novartis Investigative Site

Moscow, 115522, Russia

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Novartis Investigative Site

Moscow, 117198, Russia

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Novartis Investigative Site

Moscow, 119991, Russia

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Novartis Investigative Site

Rostov-on-Don, 344022, Russia

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Novartis Investigative Site

Saint Petersburg, 194100, Russia

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Novartis Investigative Site

Esplugues de Llobregat, Barcelona, 08950, Spain

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Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

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Novartis Investigative Site

El Palmar, Murcia, 30120, Spain

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Novartis Investigative Site

Valencia, Valencia, 46026, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Novartis Investigative Site

Lausanne, 1011, Switzerland

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Novartis Investigative Site

Istanbul, TUR, 34098, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

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Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

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Novartis Investigative Site

London, NW3 2QG, United Kingdom

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Novartis Investigative Site

London, WC1N 1EH, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 37668289 DERIVED

• 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.

  PMID: 34554243 DERIVED

• 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.

  PMID: 29768139 DERIVED

MeSH Terms

Interventions

canakinumab

Results Point of Contact

• Title: Study Director
• Organization: Novartic Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2014
• First Posted: February 11, 2014
• Study Start: June 27, 2014
• Primary Completion: July 4, 2017
• Study Completion: July 4, 2017
• Last Updated: May 17, 2018
• Results First Posted: March 17, 2017

Record last verified: 2018-04

Locations

US (3); IE (1); GB (3); NL (2); RU (5); HU (2); BE (5); DE (9); FR (4); CA (2); IT (10); ES (6); CH (1); IL (5); TU (3); JP (4)