Rheumatoid ArthritisPhase 2NCT01426789

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

A Phase 2 study testing Secukinumab in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 36 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Rheumatoid Arthritis
What is being tested?: Secukinumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 100 participants
Where: 36 sitesin 5 countries
Study dates: Aug 2011to Feb 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

36 sites in 5 countries.

Country

City, postcode or hospital

36 sites in 5 countries

United States16 sites

Novartis Investigative Site
Albuquerque, New Mexico, 87102
Novartis Investigative Site
Anahiem, California, 92804
Novartis Investigative Site
Clearwater, Florida, 33756
Novartis Investigative Site
Coral Gables, Florida, 33134
Novartis Investigative Site
Fleming Island, Florida, 32003
Novartis Investigative Site
Marietta, Georgia, 30060
Novartis Investigative Site
Miami, Florida, 33143
Novartis Investigative Site
Oklahoma City, Oklahoma, 73112
Novartis Investigative Site
Phoenix, Arizona, 85023
Novartis Investigative Site
Pinellas Park, Florida, 33781
Novartis Investigative Site
San Antonio, Texas, 78217
Novartis Investigative Site
South Bend, Indiana, 46601
Novartis Investigative Site
Springfield, Missouri, 65807
Novartis Investigative Site
Statesville, North Carolina, 28625
Novartis Investigative Site
Tuscon, Arizona, 85724
Novartis Investigative Site
Venice, Florida, 34292

Other trials in United States

Germany8 sites

Novartis Investigative Site
Berlin, 10117
Novartis Investigative Site
Berlin, 14059
Novartis Investigative Site
Frankfurt am Main, 60528
Novartis Investigative Site
Hamburg, GmbH 22769
Novartis Investigative Site
Herne, 44649
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Magdeburg, 39120
Novartis Investigative Site
München, 80336

Other trials in Germany

Russia8 sites

Novartis Investigative Site
Moscow, 117049
Novartis Investigative Site
Nizhny Novgorod, 603018
Novartis Investigative Site
Petrozavodsk, 185019
Novartis Investigative Site
Saint Petersburg, 194104
Novartis Investigative Site
Smolensk, Russia, 214019
Novartis Investigative Site
Tver', 170036
Novartis Investigative Site
Yaroslavl, 150030
Novartis Investigative Site
Yaroslavl, 150062

Other trials in Russia

Belgium2 sites

Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Kortrijk, 8500

Other trials in Belgium

United Kingdom2 sites

Novartis Investigative Site
Belfast, BT2 7BA
Novartis Investigative Site
Manchester, Manchester, M41 5SL

Other trials in United Kingdom

About this study

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

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.

Conditions: Rheumatoid Arthritis
Being tested: Placebo, Secukinumab
Keywords: Rheumatoid Arthritis, IgG1K monoclonal antibody, Interleukin-17A neutralizing
Medical subject headings: Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboDrug
Matching placebo to secukinumab I.V.
SecukinumabDrug
Also called AIN457
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.

Study groups in NCT01426789
Study group	Role	What they receive
Secukinumab	Experimental	10 mg/kg intravenous (I.V.) Receives: Drug: Secukinumab
Placebo	Placebo comparator	Placebo I.V. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 12 weeks
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.
Measured: baseline, 12 weeks

Secondary outcomes (2)

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).
Measured: 12 weeks
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.
Measured: baseline, 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2011Feb 2014

First posted31 Aug 2011 (estimated)
Study startAug 2011
Primary completionFeb 2014
Study completionFeb 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Outcomes assessor
Enrolment: 100 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01426789
Sponsor's protocol ID: CAIN457F2208
Status last verified: Aug 2015
First submitted: 12 Aug 2011
Last updated: 10 Aug 2015
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 26268815

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
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RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
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Active, not recruitingPhase 2
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Pulmonary Fibrosis, Progressive Pulmonary Fibrosis

All Rheumatoid Arthritis trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01426789
Acronym / sponsor ID: CAIN457F2208
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis, IgG1K monoclonal antibody, Interleukin-17A neutralizing
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 100 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Aug 2011
Primary completion: Feb 2014 (actual)
Study completion: Feb 2014 (actual)
First posted: 31 Aug 2011 (estimated)
Results: Posted 2 Mar 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Secukinumab	Experimental	Drug: Secukinumab10 mg/kg intravenous (I.V.)
Placebo	Placebo comparator	Drug: PlaceboPlacebo I.V.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PlaceboMatching placebo to secukinumab I.V.	Drug	Placebo
SecukinumabAlso: AIN457In 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.	Drug	Secukinumab

Primary outcome

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
Time frame: 12 weeks
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
Time frame: baseline, 12 weeks
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.

2 secondary outcomes

Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group
Time frame: 12 weeks
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
Time frame: baseline, 12 weeks

Results and safety

Results posted to the registry on 2 Mar 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Secukinumab	68	62
Placebo	32	28
Group 1	0	0
Group 2	0	0
Group 3	0	0
Group 4	0	0

Primary outcome: 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

Time frame: 12 weeks. Number. Unit: Percentage of participants

Measure	Secukinumab n = 62	Placebo n = 28
HLADRB1 *04 carriers	45.2	10.7
HLADRB1 *04 non-carriers	41.9	14.3

Population analysed: Participants, who completed part 1, were included in the analysis.

Primary outcome: Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04

Time frame: baseline, 12 weeks. Least squares mean (Standard Error). Unit: score on a scale

Measure	Secukinumab n = 62	Placebo n = 28
HLA-DRB1 *04 carriers	-2.5 (0.5273)	-0.6 (0.5750)
HLA-DRB1 *04 non-carriers	-2.2 (0.5618)	-0.8 (0.6098)

Population analysed: Participants, who completed part 1, were included in the analysis.

2 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Secukinumab	4 of 68 (5.9%)	13 of 68 (19.1%)	Not reported
Placebo	2 of 32 (6.3%)	9 of 32 (28.1%)	Not reported
Group 1	4 of 49 (8.2%)	15 of 49 (30.6%)	Not reported
Group 3	4 of 27 (14.8%)	12 of 27 (44.4%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26268815Burmester 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.

Related trials for Rheumatoid Arthritis

RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
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Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
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RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
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Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

36 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Secukinumab in people with Rheumatoid Arthritis, run by Novartis Pharmaceuticals at 36 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 36 sites in United States, Germany, Russia, Belgium, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01426789, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2015.