Back to results

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

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

secukinumab (AIN457)

placebo

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, RA, secukinumab, AIN457, inflammatory joints, American College of Rheumatology, ACR

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

secukinumab 10 mg/kg i.v. loading

secukinumab 150 mg s.c. loading

placebo

Arm Description

secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8

secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8

placebo at Weeks 0, 1, 2, 3, 4, 8 & 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).

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.

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.

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.

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'.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01359943

First Posted

May 19, 2011

Last Updated

February 12, 2015

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01359943

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

October 2011 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis, RA, secukinumab, AIN457, inflammatory joints, American College of Rheumatology, ACR

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

221 (Actual)

8. Arms, Groups, and Interventions

Arm Title

secukinumab 10 mg/kg i.v. loading

Arm Type

Experimental

Arm Description

secukinumab 10mg/kg i.v. loading at Weeks 0, 2 and 4, and placebo s.c. at weeks 0, 1, 2, 3 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8

Arm Title

secukinumab 150 mg s.c. loading

Arm Type

Experimental

Arm Description

secukinumab 150mg s.c. loading at Weeks 0, 1, 2, 3 and 4, and placebo i.v. at weeks 0, 2 and 4, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 8

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

placebo at Weeks 0, 1, 2, 3, 4, 8 & 12, followed by secukinumab 150mg s.c. every 4 weeks starting at Week 16

Intervention Type

Biological

Intervention Name(s)

secukinumab (AIN457)

Intervention Description

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).

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

Matching placebo to AIN457 i.v. and to AIN457 s.c..

Primary Outcome Measure Information:

Title

Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20)

Description

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Achieve ACR50 and ACR70

Description

Time Frame

12 weeks

Title

Change From Baseline in Health Assessment Questionnaire-Disease Index (HAQ-DI) Score.

Description

Time Frame

baseline, 12 Weeks

Title

Change From Baseline in DAS28 Using High Sensitivity C-reactive Protein (hsCRP) (DAS28-CRP)

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in Disease Activity Score 28 Response Using ESR (DAS28-ESR)

Description

Time Frame

baseline, 12 weeks

Title

Percentage of Participants With European League Against Rheumatism (EULAR) Response

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in Swollen 66-joint Count

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in Tender 68-joint Count

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in Participant's Assessment of Rheumatoid Arthritis (RA) Pain

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in Participant's Global Assessment of Disease Activity

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in Physician's Global Assessment of Disease Activity

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in hsCRP

Description

Time Frame

baseline, 12 weeks

Title

Change From Baseline in ESR

Description

Blood for this assessment was obtained to monitor disease activity and response to therapy. A negative change from baseline indicates improvement.

Time Frame

baseline, 12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Novartis Pharmceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Vestavia

State/Province

Alabama

ZIP/Postal Code

35216

Country

United States

Facility Name

Novartis Investigative Site

City

Peoria

State/Province

Arizona

ZIP/Postal Code

85381

Country

United States

Facility Name

Novartis Investigative Site

City

Upland

State/Province

California

ZIP/Postal Code

91786

Country

United States

Facility Name

Novartis Investigative Site

City

Bowling Green

State/Province

Kentucky

ZIP/Postal Code

42101

Country

United States

Facility Name

Novartis Investigative Site

City

Tupelo

State/Province

Mississippi

ZIP/Postal Code

38801

Country

United States

Facility Name

Novartis Investigative Site

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68516

Country

United States

Facility Name

Novartis Investigative Site

City

Jackson

State/Province

Tennessee

ZIP/Postal Code

38305

Country

United States

Facility Name

Novartis Investigative Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37205

Country

United States

Facility Name

Novartis Investigative Site

City

Pleven

ZIP/Postal Code

5800

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Plovdiv

ZIP/Postal Code

4000

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sevlievo

ZIP/Postal Code

5400

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1505

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1606

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

Sofia

ZIP/Postal Code

1612

Country

Bulgaria

Facility Name

Novartis Investigative Site

City

St. John's

State/Province

Newfoundland and Labrador

ZIP/Postal Code

A1C 5B8

Country

Canada

Facility Name

Novartis Investigative Site

City

Sainte-Foy

State/Province

Quebec

ZIP/Postal Code

G1W 4R4

Country

Canada

Facility Name

Novartis Investigative Site

City

Budapest

ZIP/Postal Code

1023

Country

Hungary

Facility Name

Novartis Investigative Site

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

Facility Name

Novartis Investigative Site

City

Szeged

ZIP/Postal Code

H-6725

Country

Hungary

Facility Name

Novartis Investigative Site

City

Valeggio Sul Mincio

State/Province

(vr)

ZIP/Postal Code

37067

Country

Italy

Facility Name

Novartis Investigative Site

City

Arenzano

State/Province

ZIP/Postal Code

16011

Country

Italy

Facility Name

Novartis Investigative Site

City

Genova

State/Province

ZIP/Postal Code

16132

Country

Italy

Facility Name

Novartis Investigative Site

City

Roma

State/Province

ZIP/Postal Code

00152

Country

Italy

Facility Name

Novartis Investigative Site

City

Siena

State/Province

ZIP/Postal Code

53100

Country

Italy

Facility Name

Novartis Investigative Site

City

Torino

State/Province

ZIP/Postal Code

10128

Country

Italy

Facility Name

Novartis Investigative Site

City

Bialystok

ZIP/Postal Code

15-351

Country

Poland

Facility Name

Novartis Investigative Site

City

Poznan

ZIP/Postal Code

60-218

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

ZIP/Postal Code

02-341

Country

Poland

Facility Name

Novartis Investigative Site

City

Warszawa

ZIP/Postal Code

04-141

Country

Poland

Facility Name

Novartis Investigative Site

City

San Juan

ZIP/Postal Code

00909

Country

Puerto Rico

Facility Name

Novartis Investigative Site

City

Bardejov

State/Province

Slovak Republic

ZIP/Postal Code

085 01

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Trnava

State/Province

Slovensko

ZIP/Postal Code

91701

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Lucenec

ZIP/Postal Code

98401

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Partizánske

ZIP/Postal Code

95801

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Piestany

ZIP/Postal Code

92112

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Sabinov

ZIP/Postal Code

08301

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Stara Lubovna

ZIP/Postal Code

06401

Country

Slovakia

Facility Name

Novartis Investigative Site

City

Topolcany

ZIP/Postal Code

95501

Country

Slovakia

12. IPD Sharing Statement

Citations:

PubMed Identifier

26834211

Citation

Tlustochowicz W, Rahman P, Seriolo B, Krammer G, Porter B, Widmer A, Richards HB. Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study. J Rheumatol. 2016 Mar;43(3):495-503. doi: 10.3899/jrheum.150117. Epub 2016 Feb 1.

Results Reference

derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs

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

Rheumatoid Arthritis

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial