Study of Adalimumab in Patients With Axial Spondyloarthritis

Axial Spondyloarthritis Clinical Trial

Official title:

A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Axial Spondyloarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00939003
• Other study ID #: M10-791
• Secondary ID: 2009-010643-14
• Status: Completed
• Phase: Phase 3
• First received: July 10, 2009
• Last updated: September 4, 2014
• Start date: July 2009
• Est. completion date: August 2013

Study information

• Verified date: September 2014
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Human Research Ethics CommitteeBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence francaise de securite sanitaire des produits de sante (Saint-Denis)Germany: Paul-Ehrlich-InstitutNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Agencia Española de Medicamentos y Productos SanitariosUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will evaluate how well adalimumab works in the short and long term in patients with axial spondyloarthritis who are not diagnosed as having either ankylosing spondylitis or psoriatic arthritis.

Description:

This is a Phase 3, placebo-controlled, double-blind randomized study with an open-label phase designed to evaluate the efficacy and safety of adalimumab 40 mg administered every other week in adult patients with active axial spondyloarthritis (SpA) who are not diagnosed with ankylosing spondylitis, psoriasis, or psoriatic arthritis and who have had an inadequate response or intolerance to one or more nonsteroidal anti-inflammatory drugs (NSAIDs) or had a contraindication to NSAIDs. Participants receive adalimumab or placebo for 12 weeks during the double-blind phase of the study. Following the double-blind phase, all remaining participants enter the open-label phase of the study in which they receive open-label adalimumab for up to 144 weeks. Efficacy endpoints include the Assessment of Spondyloarthritis International Society (ASAS) response criteria for patients with SpA. These response criteria were used to determine participants who were responders. ASAS response involves evaluations in the following 4 domains: participant's global assessment of disease activity, pain, function, and inflammation. The patient's global assessment of disease activity score is assessed using a 100 millimeter (mm) visual analog scale (VAS; 0 for no disease activity to 100 for severe disease activity). Pain is represented as a total back pain score and is assessed using a 100 mm VAS (0 for no pain to 100 for most severe pain). Function score is represented as the Bath Ankylosing Spondylitis (AS) Functional Index (BASFI) 100 mm VAS score (average of the ability to perform 10 activities, each scored as 0 for easy to 100 for impossible). Inflammation is determined using the morning stiffness overall level score (0 for none to 10 for very severe) and duration score (0 for 0 hours to 10 for ≥ 2 hours) of the Bath AS Disease Activity Index (BASDAI) (mean of these items #5 and #6 scores). In addition, the BASDAI is used as an efficacy endpoint. The BASDAI is used by the participant to assess his/her disease activity. Using VAS scales, the participant answers 6 questions pertaining to symptoms experienced over the past week. For 5 questions (levels of: fatigue/tiredness; AS neck, back, or hip pain; pain/swelling; discomfort at areas tender to touch or pressure; and morning stiffness), the response scale is 0 (none) to 10 (very severe). For 1 question (duration of morning stiffness), the response scale is 0 (0 hours) to 10 (≥ 2 or more hours).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: August 2013
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients with inadequate response to >/= 1 non-steroidal anti-inflammatory drugs (NSAIDs)

• Chronic back pain with onset < 45 years of age

• Magnetic resonance imaging (MRI) indicating active sacroiliitis or positive human leukocyte antigen-B27 (HLA-B27) blood test in addition to meeting spondyloarthritis clinical criteria

• Negative purified protein derivative (PPD) test and chest x-ray performed at Baseline visit must be negative

• Ability to administer subcutaneous injections

• General good health otherwise

Exclusion Criteria:

• Prior anti-tumor necrosis factor (TNF) therapy

• Psoriasis or psoriatic arthritis

• Fulfillment of modified New York criteria for ankylosing spondylitis

• Recent infection requiring treatment

• Significant medical events or conditions that may put patients at risk for participation

• Females who are pregnant or breast-feeding or considering becoming pregnant during the study

• History of cancer, except successfully treated skin cancer

• Recent history of drug or alcohol abuse

Study Design

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

Related Conditions & MeSH terms

• Axial Spondyloarthritis
• Spondylarthritis
• Spondylitis

Intervention

Biological:
• Adalimumab
40 mg every other week up to Week 12
• Placebo
Placebo every other week up to Week 12
• Open-label Adalimumab
40 mg every other week, Week 12 through Week 156

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator# 22342	Brisbane
Australia	Site Reference ID/Investigator# 21223	Kogarah
Australia	Site Reference ID/Investigator# 21222	Maroochydore
Belgium	Site Reference ID/Investigator# 21225	Genk
Belgium	Site Reference ID/Investigator# 21224	Ghent
Belgium	Site Reference ID/Investigator# 26544	Gilly
Belgium	Site Reference ID/Investigator# 27382	Merksem
Canada	Site Reference ID/Investigator# 21229	Edmonton
Canada	Site Reference ID/Investigator# 21226	Sainte-Foy, Quebec
Canada	Site Reference ID/Investigator# 21227	St. John's
Canada	Site Reference ID/Investigator# 21228	Toronto
Czech Republic	Site Reference ID/Investigator# 21231	Brno
Czech Republic	Site Reference ID/Investigator# 26882	Pardubice
Czech Republic	Site Reference ID/Investigator# 21230	Prague 2
Czech Republic	Site Reference ID/Investigator# 26883	Uherske Hradiste
France	Site Reference ID/Investigator# 21263	Boulogne Billancourt
France	Site Reference ID/Investigator# 21262	Chambray-les-Tour
France	Site Reference ID/Investigator# 21261	Orleans
France	Site Reference ID/Investigator# 22343	Paris Cedex 14
Germany	Site Reference ID/Investigator# 21266	Berlin
Germany	Site Reference ID/Investigator# 21267	Erlangen
Germany	Site Reference ID/Investigator# 21264	Herne
Germany	Site Reference ID/Investigator# 21265	Munich
Netherlands	Site Reference ID/Investigator# 21285	Amsterdam
Netherlands	Site Reference ID/Investigator# 21284	Leiden
Spain	Site Reference ID/Investigator# 21282	A Coruna
Spain	Site Reference ID/Investigator# 21283	Barcelona
Spain	Site Reference ID/Investigator# 21281	Cordoba
United Kingdom	Site Reference ID/Investigator# 21289	Newcastle upon Tyne
United States	Site Reference ID/Investigator# 21250	Birmingham	Alabama
United States	Site Reference ID/Investigator# 21249	Colorado Springs	Colorado
United States	Site Reference ID/Investigator# 21243	Dallas	Texas
United States	Site Reference ID/Investigator# 21245	Denver	Colorado
United States	Site Reference ID/Investigator# 26582	Duncansville	Pennsylvania
United States	Site Reference ID/Investigator# 21248	Houston	Texas
United States	Site Reference ID/Investigator# 21247	Seattle	Washington
United States	Site Reference ID/Investigator# 21246	Wheaton	Maryland
United States	Site Reference ID/Investigator# 21241	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czech Republic,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants Reporting Adverse Events	Adverse events were collected at designated study visits for all participants who received at least 1 dose of study drug. The number of participants experiencing any adverse event (serious and non-serious) is summarized.	Through Week 12	Yes
Other	Number of Participants With Blood Hematology or Chemistry Values Common Toxicity Criteria Grade = 3	Blood was collected for analysis at designated study visits; hematology and chemistry results were provided by a central laboratory. The number of participants with an abnormal laboratory result (higher then upper normal limit or lower than lower normal limit) meeting Common Toxicity Criteria (CTC) of Grade 3 or higher is summarized.	Through Week 12	Yes
Other	Number of Participants Achieving an ASAS20 Response During the Open-label Period	ASAS20 response was defined as improvement of = 20% relative to Baseline and absolute improvement of = 10 units (on a scale from 0 to 100) in = 3 of the following 4 domains with no deterioration (defined as a change for the worse of = 20% and net worsening of = 10 units) in the potential remaining domain: Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Baseline and Weeks 52, 104, and 156	No
Other	Number of Participants Achieving an ASAS40 Response During the Open-label Period	ASAS40 response was defined as improvement of = 40% relative to Baseline and absolute improvement of = 20 units (on a scale from 0 to 100) in = 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units on a scale of 0 to 100) in the potential remaining domain: Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Baseline and Weeks 52, 104, and 156	No
Other	Number of Participants Achieving a BASDAI50 Response During the Open-label Period	The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (= 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.	Baseline and Weeks 52, 104, and 156	No
Primary	Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response	ASAS40 response was defined as improvement of = 40% relative to Baseline and absolute improvement of = 20 units (on a scale from 0 to 100) in = 3 of the following 4 domains with no deterioration (defined as a net worsening of > 0 units on a scale from 0 to 100) in the potential remaining domain: Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Baseline and Week 12	No
Secondary	Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response	ASAS20 response was defined as improvement of = 20% relative to Baseline and absolute improvement of = 10 units (on a scale from 0 to 100) in = 3 of the following 4 domains with no deterioration (defined as a change for the worse of = 20% and net worsening of = 10 units) in the potential remaining domain: Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Baseline and Week 12	No
Secondary	Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response	The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 cm VAS) pertaining to symptoms experienced for the past week. For 5 questions (level of fatigue/tiredness, level of AS neck, back or hip pain, level of pain/swelling in joints, other than neck, back or hips, level of discomfort from any areas tender to touch or pressure, and level of morning stiffness), the response is from 0 (none) to 10 (very severe); for Question 6 (duration of morning stiffness), the response is from 0 (0 hours) to 10 (= 2 hours). The overall BASDAI score ranges from 0 to 10 cm. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from Baseline in BASDAI score.	Baseline and Week 12	No
Secondary	Change From Baseline in Short Form-36 (SF-36) Physical Component Summary Score	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life. The SF-36 consists of 36 questions in 8 domains (limitations in physical functioning due to health problems; limitations in usual role because of physical health problems; bodily pain; general health perceptions; vitality; limitations in social functioning because of physical or emotional problems; limitations in usual role due to emotional problems; and general mental health). Two component scores can be summarized: physical and mental; domains 1-4 comprise the physical component summary of the SF-36. A transformed summary score is calculated ranging from 0 to 100 where higher scores indicate a higher level of functioning. A positive change from Baseline score indicates an improvement.	Baseline and Week 12	No
Secondary	Number of Participants Achieving ASAS Partial Remission	ASAS partial remission is an absolute score of < 20 units on a 0 to 100 scale for each of the four following domains: Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none/0 hours) to 10 (very severe/2 hours or more duration).	Week 12	No
Secondary	Number of Participants Achieving an ASAS5/6 Response	ASAS5/6 response is a 20% improvement in five out of the following six domains: Patient's Global Assessment of disease activity, measured on a visual analog scale (VAS) from 0 (none) to 100 (severe); Pain, measured by the total back pain VAS from 0 (no pain) to 100 (most severe); Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on a VAS ranging from 0 (easy) to 100 (impossible); Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) VAS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none) to 10 (very severe/2 hours or more duration).; Spinal mobility, measured from the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility); C-reactive protein level (lower levels indicate less inflammation).	Baseline and Week 12	No
Secondary	Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S)	Health Assessment Questionnaire modified for spondyloarthropathies (HAQ-S) is a self-reported measure to assess the physical function and health-related quality of life. The Disability Index (DI) of HAQ-S is calculated as the mean of the following 8 category scores (range: 0 [without any difficulty] to 3 [unable to do]): Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Five additional items in the functional status measure were included in the HAQ-S, including carrying heavy packages, sitting for long periods, able to work at a flat topped table, and (if the participant had a driver's license or a car) able to look in the rear view mirror and able to turn head to drive in reverse. The overall score ranges from 0 (no disability) to 3 (three very severe, high-dependency disability). Negative mean changes from Baseline in the overall score indicate improvement.	Baseline and Week 12	No
Secondary	Change From Baseline in High-Sensitivity C-Reactive Protein (hsCRP)	C-reactive protein (CRP) is considered an efficacy variable for the axial spondyloarthritis indication. It is a general marker of inflammation that is sensitive to acute changes in inflammatory response. Higher levels indicate more inflammation.	Baseline and Week 12	No
Secondary	Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Score for Sacroiliac Joints	Six consecutive sacroiliac (SI) joint image coronal slices representing the largest proportion of the synovial compartment of the SI joints were assessed for edema, intensity and depth of edema using SPARCC scoring.; Each SI joint (left and right) was divided into quadrants for a total of 8 SI scoring locations. Each quadrant was scored for the presence (1) or absence (0) of edema; the maximum score is 8 per slice and maximum score for 6 SI joint slices is 48.; Intensity of edema: A score of 1 was assigned for each SI joint (left and right) if an intense signal was seen in any quadrant of that joint for each slice. The maximum score is 2 per slice and 12 for 6 slices.; A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the articular surface of the SI joint in any quadrant. The maximum score per slice is 2 and for 6 slices 12.; The total maximum score for all SI joints across 6 slices is 72.	Baseline and Week 12	No
Secondary	Change From Baseline in SPARCC MRI Score for the Spine	Six discovertebral units (DVU) representing the 6 most abnormal DVUs, and 3 consecutive sagittal slices at each DVU representing the most abnormal slices for that DVU were selected for scoring. Each DVU was divided into 4 quadrants and scored for the presence (1) or absence (0) of edema. The maximum score is 12 per DVU. The maximum score is 72 for 6 DVUs.; If edema was present in at least 1 quadrant of a DVU slice, it was scored for intensity and depth of the edema representing that slice: A score of 1 was assigned if an intense signal was seen in any quadrant on a DVU slice. The maximum score for intensity per slice is 1, per DVU is 3 and for 6 DVUs is 18.; A lesion was graded as deep (score of 1) if there was homogeneous and unequivocal increase in signal extending over a depth of at least 1 cm from the surface of the endplate in any quadrant. The maximum score per slice is 1, for a DVU is 3 and for 6 DVUs is 18.; The total maximum SPARCC score for all 6 DVUs is 108.	Baseline and Week 12	No

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