Infliximab for Treatment of Axial Spondyloarthritis (P05336 AM1)

Phase 3

Completed

Conditions: Ankylosing Spondylitis
Axial Spondyloarthritis

Interventions: Drug: Placebo
Drug: Infliximab
Drug: Naproxen

Registration Number: NCT00844805

Lead Sponsor: Merck Sharp & Dohme LLC

Brief 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.

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 158

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + Naproxen	Placebo	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.
Placebo + Naproxen	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.
Infliximab + Naproxen	Infliximab	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.
Infliximab + Naproxen	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.
Naproxen Only (Follow-Up)	Naproxen	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Treatment Phase	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 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	Baseline, 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.
Change From Baseline in the Sacroiliac Overall Score at Week 28	Baseline, 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.
Number of Participants Maintaining the ASAS Partial Remission Criteria at Week 52 By Treatment Assignment in the Follow-Up Phase	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 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).
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 52	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.
Median Duration of Maintaining ASAS Partial Remission in the Follow-Up Phase	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 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	Week 52	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	Week 28	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	Week 28	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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 28	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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine and Sacroiliac Joint at Treatment Week 28	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.
Change From Baseline of Berlin MRI Spine Overall Score at Week 52	Baseline, 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.
Change From Baseline in the Sacroiliac Overall Score at Week 52	Baseline, 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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 28	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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Spine at Treatment Week 52	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.
Number of Participants With Complete Absence of Active Inflammatory Lesions at the Sacroiliac Joint at Treatment Week 52	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.