Infliximab for Treatment of Axial Spondyloarthritis (P05336 AM1)

Ankylosing Spondylitis Clinical Trial

— INFAST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00844805
• Other study ID #: P05336
• Secondary ID: 2008-000982-51
• Status: Completed
• Phase: Phase 3
• First received: February 13, 2009
• Last updated: February 24, 2015
• Start date: September 2009
• Est. completion date: September 2011

Study information

• Verified date: February 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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 Spondylitis (ASAS) partial remission criteria.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: September 2011
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 48 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ankylosing Spondylitis
• Axial Spondyloarthritis
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• Infliximab

• Placebo

• Naproxen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (2)

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 ax — View Citation

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 axi — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Week 28	No
Secondary	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).	Week 52	No
Secondary	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).	Week 52	No
Secondary	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.	Baseline, Week 28	No
Secondary	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.	Baseline, Week 28	No
Secondary	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.	Baseline, Week 52	No
Secondary	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.	Baseline, Week 28	No
Secondary	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.	Week 28	No
Secondary	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.	Week 28	No
Secondary	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.	Week 28	No
Secondary	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.	Week 52	No
Secondary	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.	Week 52	No
Secondary	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.	Week 52	No
Secondary	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).	Week 52	No
Secondary	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).	Week 52	No
Secondary	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.	Week 28	No
Secondary	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.	Week 28	No