Infliximab for Treatment of Axial Spondyloarthritis (P05336 AM1) (INFAST)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme Corp.

ClinicalTrials.gov Identifier:

NCT00844805

First received: February 13, 2009

Last updated: November 7, 2014

Last verified: November 2014

History of Changes

Purpose

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.

Condition	Intervention	Phase
Ankylosing Spondylitis Axial Spondyloarthritis	Drug: Infliximab Drug: Placebo Drug: Naproxen	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Infliximab as First Line Therapy in Patients With Early Active Axial Spondyloarthritis Trial

Resource links provided by NLM:

Genetics Home Reference related topics: ankylosing spondylitis

MedlinePlus related topics: Ankylosing Spondylitis

Drug Information available for: Naproxen Naproxen sodium Infliximab

Genetic and Rare Diseases Information Center resources: Spondylarthropathy

U.S. FDA Resources

Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:

Number of Participants Achieving the Assessment in Ankylosing Spondylitis (ASAS) Partial Remission Criteria at Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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).

Secondary Outcome Measures:

Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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).
Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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).
Change From Baseline of Berlin Magnetic Resonance Imaging (MRI) Spine Overall Score at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
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.
Change From Baseline in the Sacroiliac Overall Score at Week 28 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
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.
Change From Baseline of Berlin MRI Spine Overall Score at Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]
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.
Change From Baseline in the Sacroiliac Overall Score at Week 52 [ Time Frame: Baseline, Week 28 ] [ Designated as safety issue: No ]
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28 [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52 [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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.
Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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).
Number of Participants Who Achieved ASAS Partial Remission That Experienced Disease Flare With Naproxen Maintenance Treatment in the Follow-Up Phase [ Time Frame: Week 52 ] [ Designated as safety issue: No ]
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).
Percentage of Participants That Achieved ASAS-40 Response at Week 28 in the Treatment Phase [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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.
Percentage of Participants That Achieved ASAS-20 Response at Week 28 in the Treatment Phase [ Time Frame: Week 28 ] [ Designated as safety issue: No ]
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.


Enrollment:	158
Study Start Date:	September 2009
Study Completion Date:	September 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Infliximab + Naproxen Infliximab 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.	Drug: Infliximab Other Names: Remicade SCH 215596 Drug: Naproxen Other Name: Naprosyn
Placebo Comparator: Placebo + Naproxen Placebo 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.	Drug: Placebo Drug: Naproxen Other Name: Naprosyn
Experimental: Naproxen Only (Follow-Up) For 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.	Drug: Naproxen Other Name: Naprosyn
No Intervention: No Treatment (Follow-Up) For participants who achieved partial remission during Treatment phase, no treatment was administered for an additional 24 weeks in the follow-up phase.

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).

Eligibility


Ages Eligible for Study:	18 Years to 48 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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)
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).

Exclusion Criteria:

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided

More Information

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.

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.


Responsible Party:	Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:	NCT00844805 History of Changes
Other Study ID Numbers:	P05336, 2008-000982-51
Study First Received:	February 13, 2009
Results First Received:	September 20, 2012
Last Updated:	November 7, 2014
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:


Spondylarthritis Spondylitis Spondylitis, Ankylosing Ankylosis Arthritis Bone Diseases Bone Diseases, Infectious Infection Joint Diseases Musculoskeletal Diseases Spinal Diseases Spondylarthropathies Infliximab Naproxen Analgesics	Analgesics, Non-Narcotic Anti-Inflammatory Agents Anti-Inflammatory Agents, Non-Steroidal Antirheumatic Agents Central Nervous System Agents Cyclooxygenase Inhibitors Dermatologic Agents Enzyme Inhibitors Gastrointestinal Agents Gout Suppressants Molecular Mechanisms of Pharmacological Action Peripheral Nervous System Agents Pharmacologic Actions Physiological Effects of Drugs Sensory System Agents

Spondylarthritis
Spondylitis
Spondylitis, Ankylosing
Ankylosis
Arthritis
Bone Diseases
Bone Diseases, Infectious
Infection
Joint Diseases
Musculoskeletal Diseases
Spinal Diseases
Spondylarthropathies
Infliximab
Naproxen
Analgesics

Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Dermatologic Agents
Enzyme Inhibitors
Gastrointestinal Agents
Gout Suppressants
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on February 27, 2015

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