Efficacy, Safety and Tolerability of Secukinumab in Patients With Rheumatoid Arthritis Taking Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Study of Efficacy, Safety and Tolerability of Secukinumab at 12 Weeks Administered With an Intravenous (i.v.) or Subcutaneous (s.c.) Loading Regimen Compared to Placebo in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359943
• Other study ID #: CAIN457F2206
• Secondary ID: 2010-024516-34
• Status: Completed
• Phase: Phase 2
• First received: May 19, 2011
• Last updated: February 12, 2015
• Start date: October 2011
• Est. completion date: December 2013

Study information

• Verified date: February 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBulgaria: Bulgarian Drug AgencyCanada: Health CanadaHungary: Institutional Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthPoland: The Central Register of Clinical TrialsSlovakia: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

The study compared the efficacy and assessed the safety of secukinumab given as 3 intravenous (i.v.) loading doses or weekly sub-cutaneous (s.c.) loading doses, compared to placebo, followed by monthly s.c. injections in patients with active Rheumatoid Arthritis (RA) despite treatment with Methotrexate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening

• must have been taking MTX for at least 3 months before randomization and must currently be on a stable dose of MTX for at least 4 weeks before randomization.

• At Baseline: Disease activity criteria defined by >6 tender joints out of 68 and >6 swollen joints out of 66 and with at least 1 of the following at screening: Anti-CCP antibodies positive OR Rheumatoid Factor positive and with at least 1 of the following at screening: hsCRP = 10 mg/L OR ESR = 28

Exclusion criteria:

• RA patients functional status class IV according to the ACR 1991 revised criteria

• Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-17 receptor

• Previous exposure ever to an anti-TNF-a agent or any other immunomodulatory biologic agent (experimental or approved)

• Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, or morphine)

• Any therapy by intra-articular injections (e.g. corticosteroid, hyaluronan) required for treatment of arthritis within 4 weeks before randomization

• Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• secukinumab (AIN457)
Secukinumab is a human monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind to unique proteins that your body produces. Secukinumab binds and reduces the activity of a cytokine (a "messenger" protein in the body) called Interleukin 17 (IL-17).

Drug:
• placebo
Matching placebo to AIN457 i.v. and to AIN457 s.c..

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sevlievo
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	St. John's	Newfoundland and Labrador
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Szeged
Italy	Novartis Investigative Site	Arenzano	GE
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Siena	SI
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Valeggio Sul Mincio	(vr)
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Puerto Rico	Novartis Investigative Site	San Juan
Slovakia	Novartis Investigative Site	Bardejov	Slovak Republic
Slovakia	Novartis Investigative Site	Lucenec
Slovakia	Novartis Investigative Site	Partizánske
Slovakia	Novartis Investigative Site	Piestany
Slovakia	Novartis Investigative Site	Sabinov
Slovakia	Novartis Investigative Site	Stara Lubovna
Slovakia	Novartis Investigative Site	Topolcany
Slovakia	Novartis Investigative Site	Trnava	Slovensko
United States	Novartis Investigative Site	Bowling Green	Kentucky
United States	Novartis Investigative Site	Jackson	Tennessee
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Tupelo	Mississippi
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Vestavia	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Hungary,  Italy,  Poland,  Puerto Rico,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20)	A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).	12 weeks	No
Secondary	Percentage of Participants Who Achieve ACR50 and ACR70	A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).	12 weeks	No
Secondary	Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score.	The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement.	baseline, 12 Weeks	No
Secondary	Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP)	The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28-CRP is determined using the following variables: 28-joint counts (tender28 and swollen28), CRP, and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-CRP is calculated using the following formula: DAS28-4(crp) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96. The calculation results in a DAS28-CRP score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR)	The Disease Activity Score (DAS) is a combined index to measure disease activity in RA participants. DAS28 is determined using the following variables: 28-joint counts (tender28 and swollen28), erythrocyte sedimentation rate (ESR), and the participant's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (0 = and 100 = ). Using the data from these variables, DAS28-ESR is calculated using the following formula: DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH. The calculation results in a DAS28-ESR score from 0 to 10 indicating the current activity of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6. A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Percentage of Participants With European League Against Rheumatism (EULAR) Response	EULAR response criteria are based on DAS28 status in combination with DAS28 improvements. The EULAR response criteria are as follows: present DAS28 <3.2 with DAS28 improvement >1.2 corresponds to 'good response'; present DAS28 <3.2 with DAS28 improvement between 0.6 to 1.2, or present DAS28 between 3.2 to 5.1 with DAS28 improvement from 0.6 to >1.2, or present DAS28 >5.2 with DAS28 improvement >1.2 correspond to 'moderate response; present DAS28 <3.2 with DAS28 improvement <0.6, or present DAS28 between 3.2 to 5.1 with DAS28 improvement <0.6, or present DAS28 >5.1 with DAS28 improvement <0.6 to 1.2 correspond to 'no response'.	baseline, 12 weeks	No
Secondary	Change From Baseline in Swollen 66-joint Count	The 66 joints assessed for swelling included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Swelling was graded present (1) or absent (0). A negative change in baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in Tender 68-joint Count	The 68 joints assessed for tenderness included the 8 distal interphalangeal, 10 proximal interphalangeal and 10 metacarpophalangeal joints of the hands, the 10 metatarsophalangeal and 10 proximal interphalangeal joints of the feet, the 2 wrists, 2 elbows , 2 shoulders , 2 acromioclavicular, 2 sternoclavicular, 2 temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. Joint tenderness was graded present (1) or absent (0). A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain	The patient's assessment of pain was performed using 100 mm visual analog scale (VAS) ranging from 0 (no pain) to 100 (unbearable pain) after the question "Please indicate with a vertical mark through the horizontal line the most pain you had from your rheumatoid arthritis over the last 24 hours". A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in Participant's Global Assessment of Disease Activity	The patient's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question "Considering all the ways rheumatoid arthritis affects you, please indicate with a vertical mark through the horizontal line how well you are doing today". A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in Physician's Global Assessment of Disease Activity	The physician's global assessment of disease activity was performed using 100 mm VAS ranging from 0 (very good) to 100 (very poor), after the question "Considering all the ways rheumatoid arthritis affects your patient, how would you rate his or her current condition?". A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in hsCRP	Blood for this assessment was obtained to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A negative change from baseline indicates improvement.	baseline, 12 weeks	No
Secondary	Change From Baseline in ESR	Blood for this assessment was obtained to monitor disease activity and response to therapy. A negative change from baseline indicates improvement.	baseline, 12 weeks	No