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A Biomarker Study of Secukinumab in Rheumatoid Arthritis (RA) Patients

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Secukinumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, IgG1K monoclonal antibody, Interleukin-17A neutralizing

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of rheumatoid arthritis
  • Patients must be either DMARD naive or have failed at least one DMARD agent (e.g. MTX, leflunamide or sulfasalazine)
  • Patients are allowed up to 3 DMARDs at study entry (e.g. MTX, sulfasalazine or hydroxychloroquine) as long as their dose was stable for 4 weeks prior to initiating study treatment
  • Disease activity at screening defined by ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints and hsCRP >10mg/L

Exclusion Criteria:

  • Patients with severe rheumatoid arthritis (functional status class IV according to the ACR 1991 revised criteria)
  • Previous exposure to secukinumab or any other biologic, including TNF inhibitors.
  • Use of high potency opioid analgesics
  • Pregnant or nursing (lactating) women
  • Use of any investigational drug other than RA therapy and/or devices at the time of randomization or within 30 days or 5 half-lives of randomization, whichever is longer.

Other protocol-defined inclusion/exclusion criteria may apply

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Secukinumab

Placebo

Arm Description

10 mg/kg intravenous (I.V.)

Placebo I.V.

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20 ) in Association With the Presence or Absence of the HLA-DRB1 *4 Allelic Group
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).
Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04
The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement.

Secondary Outcome Measures

Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group
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 DAS28 in Association With the Presence or Absence of HLA-DRB1 *SE (Positive), HLA-DRB1 *401 (Carrier) and HLA-DRB1 Position 11 V/L and in Association With Other Biomarkers
The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement.

Full Information

First Posted
August 12, 2011
Last Updated
August 6, 2015
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01426789
Brief Title
A Biomarker Study of Secukinumab in Rheumatoid Arthritis (RA) Patients
Official Title
A Multicenter, 12 Week, Randomized, Double-blind, Placebo-controlled Biomarker Study of Secukinumab (AIN457) in Rheumatoid Arthritis Patients Followed by an Open Label Extension
Study Type
Interventional

2. Study Status

Record Verification Date
August 2015
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary
This study aims to confirm if patients with a specific biomarker might have a better response to secukinumab treatment. To meet this purpose, exploratory biomarker studies will be done. The goals of these exploratory studies are to (1) find biomarkers that will identify persons with rheumatoid arthritis who will have the best possible response to secukinumab and (2) to identify persons who will have fewer side effects in order to maximize their benefit from secukinumab.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid Arthritis, IgG1K monoclonal antibody, Interleukin-17A neutralizing

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Secukinumab
Arm Type
Experimental
Arm Description
10 mg/kg intravenous (I.V.)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo I.V.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo to secukinumab I.V.
Intervention Type
Drug
Intervention Name(s)
Secukinumab
Other Intervention Name(s)
AIN457
Intervention Description
In part 1 (blinded period), participants randomized to secukinumab received 10 mg/kg I.V.. Participants, enrolled in part 2 (open label), received secukinumab 300 mg subcutaneous.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20 ) in Association With the Presence or Absence of the HLA-DRB1 *4 Allelic Group
Description
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).
Time Frame
12 weeks
Title
Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04
Description
The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement.
Time Frame
baseline, 12 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group
Description
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).
Time Frame
12 weeks
Title
Change From Baseline in DAS28 in Association With the Presence or Absence of HLA-DRB1 *SE (Positive), HLA-DRB1 *401 (Carrier) and HLA-DRB1 Position 11 V/L and in Association With Other Biomarkers
Description
The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. 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
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of rheumatoid arthritis Patients must be either DMARD naive or have failed at least one DMARD agent (e.g. MTX, leflunamide or sulfasalazine) Patients are allowed up to 3 DMARDs at study entry (e.g. MTX, sulfasalazine or hydroxychloroquine) as long as their dose was stable for 4 weeks prior to initiating study treatment Disease activity at screening defined by ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints and hsCRP >10mg/L Exclusion Criteria: Patients with severe rheumatoid arthritis (functional status class IV according to the ACR 1991 revised criteria) Previous exposure to secukinumab or any other biologic, including TNF inhibitors. Use of high potency opioid analgesics Pregnant or nursing (lactating) women Use of any investigational drug other than RA therapy and/or devices at the time of randomization or within 30 days or 5 half-lives of randomization, whichever is longer. 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
Facility Information:
Facility Name
Novartis Investigative Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85023
Country
United States
Facility Name
Novartis Investigative Site
City
Tuscon
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
Novartis Investigative Site
City
Anahiem
State/Province
California
ZIP/Postal Code
92804
Country
United States
Facility Name
Novartis Investigative Site
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Novartis Investigative Site
City
Coral Gables
State/Province
Florida
ZIP/Postal Code
33134
Country
United States
Facility Name
Novartis Investigative Site
City
Fleming Island
State/Province
Florida
ZIP/Postal Code
32003
Country
United States
Facility Name
Novartis Investigative Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33143
Country
United States
Facility Name
Novartis Investigative Site
City
Pinellas Park
State/Province
Florida
ZIP/Postal Code
33781
Country
United States
Facility Name
Novartis Investigative Site
City
Venice
State/Province
Florida
ZIP/Postal Code
34292
Country
United States
Facility Name
Novartis Investigative Site
City
Marietta
State/Province
Georgia
ZIP/Postal Code
30060
Country
United States
Facility Name
Novartis Investigative Site
City
South Bend
State/Province
Indiana
ZIP/Postal Code
46601
Country
United States
Facility Name
Novartis Investigative Site
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65807
Country
United States
Facility Name
Novartis Investigative Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87102
Country
United States
Facility Name
Novartis Investigative Site
City
Statesville
State/Province
North Carolina
ZIP/Postal Code
28625
Country
United States
Facility Name
Novartis Investigative Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Novartis Investigative Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78217
Country
United States
Facility Name
Novartis Investigative Site
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Novartis Investigative Site
City
Kortrijk
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
14059
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt am Main
ZIP/Postal Code
60528
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
GmbH 22769
Country
Germany
Facility Name
Novartis Investigative Site
City
Herne
ZIP/Postal Code
44649
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Magdeburg
ZIP/Postal Code
39120
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
80336
Country
Germany
Facility Name
Novartis Investigative Site
City
Smolensk
State/Province
Russia
ZIP/Postal Code
214019
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
117049
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Nizhny Novgorod
ZIP/Postal Code
603018
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Petrozavodsk
ZIP/Postal Code
185019
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
St.Petersburg
ZIP/Postal Code
194104
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Tver
ZIP/Postal Code
170036
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Yaroslavl
ZIP/Postal Code
150030
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Yaroslavl
ZIP/Postal Code
150062
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Belfast
ZIP/Postal Code
BT2 7BA
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M41 5SL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
26268815
Citation
Burmester GR, Durez P, Shestakova G, Genovese MC, Schulze-Koops H, Li Y, Wang YA, Lewitzky S, Koroleva I, Berneis AA, Lee DM, Hueber W. Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin-17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology (Oxford). 2016 Jan;55(1):49-55. doi: 10.1093/rheumatology/kev258. Epub 2015 Aug 12.
Results Reference
derived

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A Biomarker Study of Secukinumab in Rheumatoid Arthritis (RA) Patients

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