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

Hereditary Periodic Fevers Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02059291
• Other study ID #: CACZ885N2301
• Status: Completed
• Phase: Phase 3
• Start date: June 27, 2014
• Est. completion date: July 4, 2017

Study information

• Verified date: April 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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:

1. Epoch 1: a screening epoch to assess participant's eligibility;

2. 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

3. 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;

4. Epoch 4: an open-label treatment epoch of 72 weeks to collect long-term

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: July 4, 2017
• Est. primary completion date: July 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Familial Mediterranean Fever
• Fever
• Hereditary Autoinflammatory Diseases
• Hereditary Periodic Fevers

Intervention

Drug:
• Canakinumab
Canakinumab solution for subcutaneous injection in vial which contained 150mg/mL canakinumab in 1 mL solution.
• Placebo
Matching placebo to canakinumab solution for subcutaneous injection

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Vancouver	British Columbia
France	Novartis Investigative Site	Bron Cedex
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Nimes Cedex
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Germering
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Saint Augustin
Germany	Novartis Investigative Site	Tübingen
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Ireland	Novartis Investigative Site	Galway
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach-Tikva
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Brescia	BS
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Messina	ME
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma
Italy	Novartis Investigative Site	Sciacca	AG
Italy	Novartis Investigative Site	Trieste	TS
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Sakyo-ku	Kyoto
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Utrecht
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Rostov on Don
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Esplugues de Llobregat	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Lausanne
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul	TUR
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Netherlands,  Russian Federation,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	16 weeks
Secondary	Percentage of Participants With the Serologic Remission	Serologic remission was defined as C-reactive protein <= 10 mg/L.	16 weeks
Secondary	Percentage of Participants With Normalized Serum Amyloid A (SAA) Level	Normalized SAA was defined as SAA <= 10 mg/L.	16 weeks
Secondary	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.	40 weeks