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Ankylosing SpondylitisPhase 3INFASTNCT00844805

Infliximab for Treatment of Axial Spondyloarthritis (P05336 AM1)

A Phase 3 study testing Infliximab and Naproxen in people with Ankylosing Spondylitis and Axial Spondyloarthritis, run by Merck Sharp & Dohme LLC.

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

The primary objective of this study was to assess the proportion of participants in the infliximab plus naproxen arm versus the placebo plus naproxen arm, in a population of participants with moderate-to-severe active axial spondyloarthritis and disease duration of ≤3 years, who achieve the Assessment in Ankylosing… Read more about this study

Who is it for?
Ages 18 to 48 years
What is being tested?
Infliximab and Naproxen
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
158 participants
Where
No sites listed yet
Study dates
Sep 2009to Sep 2011
Phase
Phase 3
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 to 48 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Participant must:
  • be 18 to 48 years of age
  • have diagnosis of active axial spondyloarthritis, with disease duration of less than or equal to 3 years.
  • have active disease during trial enrollment
  • have limited treatment history for axial spondyloarthritis (must meet certain criteria)
  • agree to an acceptable method of contraception (for women of childbearing potential and all men)
Show all 9Show fewer
  • must meet certain tuberculosis screening requirements
  • must meet certain laboratory screening safety requirements
  • have an x-ray of the sacroiliac joints available from within the previous 12 months (or have one performed during the Screening visit if site is outside of Germany).

Who cannot join

  • Participant will be excluded:
  • for certain medical conditions and/or recent history of certain medical disorders
  • for current or recent treatment with certain other medications and certain vaccinations.
  • for being a woman who is breastfeeding, pregnant, or intending to become pregnant.
  • if known to have had a substance abuse problem within the previous 3 years prior to screening.
  • if currently participating in any other clinical study.
  • for other administrative reasons.

About this study

Official title: Infliximab as First Line Therapy in Patients With Early Active Axial Spondyloarthritis Trial

The primary objective of this study was to assess the proportion of participants in the infliximab plus naproxen arm versus the placebo plus naproxen arm, in a population of participants with moderate-to-severe active axial spondyloarthritis and disease duration of ≤3 years, who achieve the Assessment in Ankylosing Spondylitis (ASAS) partial remission criteria.

Read the detailed description

In the 28-week treatment phase, participants were randomized to receive either infliximab plus naproxen or placebo plus naproxen.

After 28-weeks of treatment, participants that achieved partial remission in the treatment phase were randomized to continued treatment with naproxen or to receive no treatment and were followed for an additional 24 weeks (follow-up phase).

Being tested
Infliximab, Placebo, Naproxen
Medical subject headings
Spondylitis, Ankylosing, Axial Spondyloarthritis

What participants receive

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

  • InfliximabDrug

    Also called Remicade, SCH 215596

  • PlaceboDrug

  • NaproxenDrug

    Also called Naprosyn

Study groups in NCT00844805
Study groupRoleWhat they receive
Infliximab + NaproxenExperimentalInfliximab administered at a dose of 5 mg/kg intravenously on Day 1 of Weeks 0, 2, 6, 12, 18, and 24, combined with naproxen administered at a daily dose of 1000 mg for 28 weeks during the 28-week treatment phase.
Receives: Drug: Infliximab; Drug: Naproxen
Placebo + NaproxenPlacebo comparatorPlacebo administered intravenously on Day 1 at Weeks 0, 2, 6, 12, 18, and 24, combined with naproxen administered at a daily dose of 1000 mg for 28 weeks, during the 28-week treatment phase.
Receives: Drug: Placebo; Drug: Naproxen
Naproxen Only (Follow-Up)ExperimentalFor participants who achieved partial remission during 28-week treatment phase, naproxen was continued at a daily dose of 1000 mg administered orally for an additional 24 weeks in the follow-up phase.
Receives: Drug: Naproxen
No Treatment (Follow-Up)No interventionFor participants who achieved partial remission during Treatment phase, no treatment was administered for an additional 24 weeks in the follow-up phase.

What is being measured

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

  1. Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28

    ASAS domains were measured on a visual analog scale (VAS) of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).

    Measured: Week 28

Secondary outcomes (16)
  1. Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase

    ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).

    Measured: Week 52

  2. Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase

    ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worst situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).

    Measured: Week 52

  3. Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28

    MRI scans (T1 for chronic changes and short tau inversion recovery [STIR] for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.

    Measured: Baseline, Week 28

  4. Change From Baseline in the Sacroiliac Overall Score at Week 28

    Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.

    Measured: Baseline, Week 28

  5. Change From Baseline of Berlin MRI Spine Overall Score at Week 52

    MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.

    Measured: Baseline, Week 52

  6. Change From Baseline in the Sacroiliac Overall Score at Week 52

    Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable.

    Measured: Baseline, Week 28

  7. Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28

    MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0.

    Measured: Week 28

  8. Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28

    Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions at the sacroiliac joints was defined as a Score = 0.

    Measured: Week 28

  9. Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28

    MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0.

    Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0.

    Measured: Week 28

  10. Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52

    MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active inflammatory lesions was defined as a Berlin MRI Score = 0.

    Measured: Week 52

  11. Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52

    EaEach sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0.

    Measured: Week 52

  12. Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52

    MRI scans (T1 for chronic changes and STIR for active changes) of the whole spine was performed to determine the Berlin MRI Spine Score. The Berlin MRI scoring for the spine was assessed on a scale of 0 (best) to 3 (worst) for a maximum total score of 69, with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active spinal inflammatory lesions was defined as a Berlin MRI Score = 0.

    Each sacroiliac joint was divided into four quadrants. An activity score of 0 (best) to 3 (worst) was assessed for every quadrant of the left and right sacroiliac joint separately for a total maximum score of 24, with with 0 = no inflammatory lesions; 1 = minor bone marrow edema; 2 = moderate bone marrow edema; 3 = major bone marrow edema; or N = non readable. Complete absence of active sacroiliac inflammatory lesions was defined as a Score = 0.

    Measured: Week 52

  13. Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase

    ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS partial remission criteria is defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).

    Measured: Week 52

  14. Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase

    The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) employs a VAS of 0mm (best) to 100mm (worst). Disease flare was defined as reaching a BASDAI of ≥30 mm during two consecutive visits after Week 28 until Week 52.

    ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS partial remission criteria was defined as reaching ≤20 mm in all 4 ASAS domains (i.e., patient global assessment, total back pain, function, and inflammation).

    Measured: Week 52

  15. Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase

    ASAS domains were measured on a VAS of 0 to 100 mm (with 0 being the very best situation and 100 being the very worse situation). ASAS-40 response was defined as ASAS achieving ≥40% improvement in 3 of the 4 domains (patient global assessment, total back pain, function, and inflammation), with an absolute improvement of ≥20 mm and no deterioration in the remaining domain.

    Measured: Week 28

  16. Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase

    ASAS-20 response was defined as ≥20% improvement in response according to following criteria:

    • An improvement of ≥20% from baseline and an absolute improvement from baseline of ≥10 mm in at least 3 of the following 4 domains (patient global assessment, pain, function,and inflammation)
    • Absence of deterioration from baseline (≥20% and an absolute change of

    ≥10 mm) in the potential remaining domain.

    Measured: Week 28

Timeline

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

  1. First posted16 Feb 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionApr 2011
  4. Study completionSep 2011

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
158 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00844805
Sponsor's protocol ID
P05336
Other IDs
2008-000982-51, 2008
Acronym
INFAST
Status last verified
Mar 2017
First submitted
13 Feb 2009
Last updated
12 Apr 2017
Data monitoring committee
No
Individual data sharing
Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php

Publications

  • Sieper J, Lenaerts J, Wollenhaupt J, Rudwaleit M, Mazurov VI, Myasoutova L, Park S, Song Y, Yao R, Chitkara D, Vastesaeger N; All INFAST Investigators. Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1. Ann Rheum Dis. 2014 Jan;73(1):101-7. doi: 10.1136/annrheumdis-2012-203201. Epub 2013 May 21.

    PubMed 23696633
  • Sieper J, Lenaerts J, Wollenhaupt J, Rudwaleit M, Mazurov VI, Myasoutova L, Park S, Song Y, Yao R, Chitkara D, Vastesaeger N; All INFAST Investigators. Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2. Ann Rheum Dis. 2014 Jan;73(1):108-13. doi: 10.1136/annrheumdis-2013-203460. Epub 2013 Jun 5.

    PubMed 23740231
  • Poddubnyy D, Listing J, Sieper J. Brief Report: Course of Active Inflammatory and Fatty Lesions in Patients With Early Axial Spondyloarthritis Treated With Infliximab Plus Naproxen as Compared to Naproxen Alone: Results From the Infliximab As First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial. Arthritis Rheumatol. 2016 Aug;68(8):1899-903. doi: 10.1002/art.39690.

    PubMed 27015283

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Infliximab and Naproxen in people with Ankylosing Spondylitis and Axial Spondyloarthritis, run by Merck Sharp & Dohme LLC.

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 9 inclusion and 7 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 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 17 Dec 2012). 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?

Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 (time frame: Week 28). 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 NCT00844805, which also lists 3 linked publications.

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 12 Apr 2017.

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