Completed
ATLAS

Human Anti-tumor Necrosis Factor (TNF) Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis

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What is being tested

adalimumab (D2E7)

+ placebo
Biological
Who is being recruted

Ankylosing Spondylitis

Over 18 Years
+13 Eligibility Criteria
How is the trial designed

Treatment Study

Placebo-Controlled
Phase 3
Interventional
Study Start: January 2004

Summary

Principal SponsorAbbott
Last updated: April 21, 2011
Sourced from a government-validated database.Claim as a partner
Study start date: January 1, 2004Actual date on which the first participant was enrolled.

The objective of this study was to evaluate the safety and efficacy of adalimumab 40 mg given every other week (eow) in subjects with active ankylosing spondylitis (AS) who have had an inadequate response to, or who are intolerant to, treatment with at least 1 nonsteroidal anti-inflammatory drug (NSAID) and who may have also failed treatment with at least 1 disease-modifying antirheumatic drug (DMARD).

Official TitleA Phase 3 Multicenter Study of the Safety and Efficacy of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Active Ankylosing Spondylitis 
Principal SponsorAbbott
Last updated: April 21, 2011
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
315 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a placebo-controlled study, some participants receive the experimental treatment, while others receive an inert substance (placebo) to compare outcomes. This method helps to isolate the effect of the treatment from the psychological effects of receiving any treatment at all.

Other Options
Non-placebo-controlled
: No placebo is used. All participants receive the actual treatment or alternative interventions (often the Standard of Care), and comparisons are made between these treatments.

How the interventions assigned to participants is kept confidential
Neither participants nor researchers know who is receiving which treatment. This is the most rigorous way to reduce bias, ensuring that expectations do not influence the results.

Other Ways to Mask Information
Open-label
: Everyone knows which treatment is being given.

Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Ankylosing Spondylitis
Criteria
5 inclusion criteria required to participate
Subjects must be >= 18 years of age

meet Modified NY Criteria definition of ankylosing spondylitis (AS)

have diagnosis of active AS based on protocol specified criteria

inadequate response or intolerance to >= 1 nonsteroidal antiinflammatory drug (NSAID)


8 exclusion criteria prevent from participating
Active tuberculosis, listeriosis,or hepatitis B, or any history of hepatitis C

History of demyelinating disease, multiple sclerosis, cancer, or lymphoproliferative disease

Previous anti-tumor necrosis factor therapy

Treatment with disease-modifying antirheumatic drugs (DMARDs - other than methotrexate, hydroxychloroquine, and sulfasalazine)


Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

50% chance 

of being blinded to the placebo group

Treatment Groups
Group I
Experimental
Group II
Placebo
Study Objectives
Primary Objectives

ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 \[none\]-100 \[severe\]), Total Back Pain VAS (0 \[no pain\]-100 \[severe\]), BASFI VAS (0 \[easy\]-100\[impossible\]); and Inflammation VAS (0 \[none\]-10 \[very severe\]) and absence of deterioration in the potential remaining domain, defined as a worsening of \>=20% and a net worsening of \>=10 units. Applied to each scale and not to an overall global scale.

Radiographic progression was based on change in mSASSS scoring (comparison of the means) from double-blind Baseline visit to Week 104. The mSASSS is the sum of the lumbar and cervical spine score ( 0 \[no change\] to 72 \[progression\]), derived from scoring the anterior site of the lumbar spine (T12 to S1) and the cervical spine (C2 to T1) as either 0 (normal), 1 (erosion, sclerosis, or squaring), 2 (syndesmophyte), 3 (bridging syndesmophyte), or N (vertebral body not evaluable). Data from NCT00195819 was compared with data from AS patients in OASIS.
Secondary Objectives

ASAS 20 responders - improvement of \>=20% and absolute improvement of \>=10 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS; (0\[none\]-100 \[severe\]), Total Back Pain VAS; (0 \[no pain\]-100 \[severe\]), BASFI VAS (0 \[easy \]-100\[impossible\]); and Inflammation VAS (0 \[none\] to 10 \[very severe\]) and absence of deterioration in the potential remaining domain, defined as a worsening of \>=20% and a net worsening of \>=10 units. Applied to each scale and not to an overall global scale.

ASAS 50 responders - improvement of \>=50% and absolute improvement of \>=20 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains: Patient's Global Assessment of disease activity VAS (0 \[none\] to 100 \[severe\]); Total Back Pain VAS (0 \[no pain\] to 100 \[severe\]); BASFI VAS (0 \[easy\] to 100\[impossible\]); and Inflammation VAS (1 \[none\] to 10 \[very severe\]); and absence of deterioration in the potential remaining domain, defined as a worsening of \>=20% and a net worsening of \>=10 units. Applied to each scale and not to an overall global scale.

ASAS 70 responders - improvement of \>=70% and absolute improvement of \>=30 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains: Patient's Global Assessment of disease activity VAS (0 \[none\] to 100 \[severe\]), Total Back Pain VAS; (0 \[no pain\] - 100 \[severe\]), BASFI VAS (0 \[easy\] to 100\[impossible\]); and Inflammation VAS (1 \[none\] to 10 \[very severe\]); and absence of deterioration in the potential remaining domain, defined as defined as a worsening of \>= 20% and a net worsening of \>= 10 units. Applied to each scale and not to an overall global scale.

Evaluation of the effect of adalimumab 40 mg every other week (eow) on patient's global assessment of disease activity. The patient was to assess his/her disease activity in the past week using a visual analog scale (VAS) on a scale of 0 to 100 mm with no activity being indicated by 0 and severe activity by 100.

The patient assesses his/her disease activity for the past week using a Patient Global Assessment of Disease on visual analog scale (VAS) with 0 being none and 100 being severe.

BASFI consist of a set of 10 questions designed to determine the degree of functional limitation in subjects with AS. The BASFI score was derived based on the average of questions 1 through 10. The first 8 questions considered activities related to functional anatomy and the final 2 questions assessed the subject's ability to cope with everyday life over the last week. A 100-mm visual analog scale (VAS) was used to answer the questions and the mean of the ten scales gave the BASFI score a value between 0 (easy) and 100 (impossible).

BASFI consisted of 10 Visual Analog Scale (VAS) questions with a response ranging from 0 (easy) to 100 (impossible). The BASFI score was derived based on the average of questions 1 through 10. A responder is a subject who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline.

Evaluation of the effect of 40 mg every other week (eow) adalimumab on Total Back Pain VAS. The subject was to assess his/her disease activity in the past week using a total spine VAS on a scale 0 (no pain) to 100 (severe pain).

Participants assessed disease activity in the past week using a total spine VAS on a scale 0 (no pain) to 100 (severe pain). A responder is a participant who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline.

The inflammation score is the mean of the two morning stiffness-related BASDAI visual analog scale (VAS) scores (items 5 and 6 of the BASDAI): overall level of morning stiffness (0 \[none\] to 10 \[very severe\]) and duration of morning stiffness (0 \[0 hours\] to 10 \[2 or more hours\]). A decrease in inflammation represents improvement.

The inflammation score is the mean of the two morning stiffness-related BASDAI visual analog scale (VAS) scores (items 5 and 6 of the BASDAI): overall level of morning stiffness (0 \[none\] to 10 \[very severe\]) and duration of morning stiffness (0 \[0 hours\] to 10 \[2 or more hours\]). A decrease in inflammation represents improvement. A responder is a participant who demonstrates an absolute improvement of at least 10 units and a percentage improvement of at least 20% from Baseline in inflammation (mean of the BASDAI questions 5 and 6 on scale of 0 \[none\] to 10 \[very severe\].

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 (none) to 10 (very severe). Improvement in BASDAI by 20% was assessed. BASDAI Scoring: Measure each item of the BASDAI in centimeters (out of a total of 10) BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. Improvement in BASDAI by 50% was assessed. BASDAI Scoring: Measure each item of the BASDAI in centimeters (out of a total of 10) BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 to 10. Improvement in BASDAI by 70% was assessed. BASDAI Scoring: Measure each item of the BASDAI in centimeters (out of a total of 10) BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

The BASDAI is a questionnaire with 6 questions that subject completes by marking answers on a 10-cm Visual Analog Scale (VAS) during the last week with responses that range from 0 (none) to 10 (very severe) and measures severity of fatigue, spinal and peripheral joint pain, localized tenderness and morning stiffness. The final BASDAI score ranges from 0 (none) to 10 (severe). A decrease in BASDAI represents improvement. BASDAI Scoring: 1) Measure each item of the BASDAI in centimeters (out of a total of 10) 2) BASDAI Score = 0.2 (Item 1 + Item 2 + Item 3 + Item 4 + Item 5/2 + Item 6/2).

Evaluation of the mean changes in CRP in subjects with adalimumab exposure from Baseline through 5 years. The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation via the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation. A decrease in CRP indicates improvement.

ASAS 40 responders - improvement of \>=40% and absolute improvement of \>=20 units from Baseline in a visual analog scale (VAS) for \>=3 of 4 domains; Patient's Global Assessment of disease activity VAS (0 \[none\] to 100 \[severe\]); Total Back Pain VAS (0 \[no pain\] to 100 \[severe\]); BASFI VAS (0 \[easy\] to 100\[impossible\]); and Inflammation VAS (1 \[none\] to 10 \[very severe\]); and absence of any deterioration in the potential remaining domain. Applied to each scale and not to an overall global scale.

The change in ASAS 5/6 was evaluated for the effect of adalimumab on structural damage. ASAS 5/6 criteria is the 20% improvement in 5 out of 6 domains (physical function \[BASFI\], Total Back Pain, Patient's Global Assessment of Disease Activity, Inflammation \[mean of Questions 5 and 6 of the BASDAI\], spinal mobility \[BASMI\], and acute phase reactants \[CRP\]).

ASAS partial remission was calculated as follows: A value below 20 on a 0 - 100 point scale in each of the four domains of the ASAS (Patient's Global Assessment of Disease Activity, Pain, Function, and Inflammation). Partial remission is also regarded as a low disease activity state.

BASMI measures the range of motion based on five clinical measurements: 1) cervical rotation, 2) tragus to wall distance, 3) lumbar side flexion, 4) lumbar flexion (modified Schober's) and 5) intermalleolar distance. BASMI 0 = indicates mild disease involvement, 1 = moderate disease, and 2 = severe disease involvement. The results for cervical rotation and lumbar side flexion are the means of the left and right measurements. Scoring range 0-10. The higher the BASMI score, the more severe was the subject's limitation of movement due to their AS.

The patient is in a sitting position on the examination table with the hands on the hips. A pen mark is made at the xiphisternum and a tape measure placed around the circumference of the patient's chest at this level. The patient is asked to take a deep breath and to exhale as completely as possible while looking directly ahead. The measurement (in cm) is noted. The patient is asked to inhale as deeply as possible and the measurement (in cm) is noted. The difference in the 2 measurement points (in cm) constitutes the value for CE. An increase in chest expansion represents improvement

MASES is measured by scoring of entheses of 0 (no tenderness) to 3 (severe tenderness) at 13 sites on the body. The score was derived as the sum of the 13 scores divided by 3 and the total range is 0 to 13 (minimum to maximum number and severity of enthesitis).

BAS-G was measured by two VAS scores (0 to 100 mm) to reflect the effect of Ankylosing Spondylitis on subject's well-being over the past week and over the last 6 months, respectively. The average of these two scores was reported.

Change from Baseline in the swollen joint index. An assessment of 44 joints for SJC done by physical examination. Joint swelling was classified as present ("1"), absent ("0") or injected/replaced ("9"). The joints assessed were: Sternoclavicular, Acromioclavicular, Shoulder, Elbow, Wrist, Metacarpophalangeal (1-5), Thumb interphalangeal, Proximal interphalangeal (2-5, Knee, Ankle, and Metatarsophalangeal (1-5).

Assessment of 46 joints for TJC was done by physical examination. Joint tenderness was classified as present ("1"), absent ("0") or injected/replaced ("9"). The joints assessed were: Sternoclavicular, Acromioclavicular, Shoulder, Elbow, Wrist, Metacarpophalangeal (1-5), Thumb interphalangeal, Proximal interphalangeal (2-5, Hip, Knee, Ankle, and Metatarsophalangeal (1-5).

The physician will globally assess the subject's current disease state using a 100-mm VAS scale with 0 being very good and 100 being very bad.

The subject was to assess his/her nocturnal pain intensity for the past week using a Nocturnal Pain Visual Analog Scale (Nocturnal Pain VAS). The range was 0 to 100 mm with no pain being indicated by 0 and worse possible pain by 100.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0 (no functioning) to 100 (highest level of functioning). The SF-36 Health Survey Index was completed by participants. Components of the SF-36 included the PCS and MCS, respectively. An increase in SF-36 PCS or MCS indicated improvement.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0(no functioning) to 100 (highest level of functioning). Responders were subjects whose change in PCS score fulfilled the Minimal Clinically Important Difference (MCID). The MCID for PCS was determined by a \>= 3.0 point increase during exposure to adalimumab.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0 (no functioning) to 100 (highest level of functioning). The SF-36 Health Survey Index was completed by participants. Components of the SF-36 included the PCS and MCS, respectively. An increase in SF-36 PCS or MCS indicated improvement.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being; physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for a section is an average of the individual question scores, which are scaled 0(no functioning) to 100 (highest level of functioning). Responders were subjects whose change in MCS fulfilled the Minimal Clinically Important Difference (MCID). The MCID for MCS was determined by a \>= 3.0 point increase during exposure to adalimumab.

The HUI-3 is a generic approach to the measurement of health status and assessment of health-related quality of life (HRQL). The HUI-3 classification is comprised of a total score and 8 attributes - Vision, Hearing, Speech, Ambulation, Dexterity, Emotion, Cognition and Pain. The attributes are measures on a scale from the worst score of 0 to best score of 1. The total score scale ranges from dead (= 0) and perfect health (= 1). The total score can have a negative score that is interpreted as worse than dead and the lower limit is -0.36. An increase in the HUI-3 score represents improvement.

ASQoL determined participants' quality of life and is comprised of 18 questions (yes or no) to be completed by the participant. Each statement on the ASQoL is given a score of "1" or "0." All item scores were summed to give a total score or index. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement.

ASQoL determined participants' quality of life and is comprised of 18 questions (yes or no) to be completed by the participant. Total scores ranged from 0 (good quality of life) to 18 (poor quality of life) related to ability to cope, relationships, mood, sleep, motivation, activities of everyday living, independence, and social life. Decrease in ASQoL score represents improvement. Responders are participants with a minimal clinically important difference (MCID) \<= -1.8 points. MCID was determined by a \>= 1.8 score decrease during exposure to adalimumab.

Completed by subject at each visit. The Patient Acceptable Symptoms State (PASS) was a participant-reported outcome where participants were expected to respond (yes/no) to the following question: Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 22 locations
Suspended
Unknown FacilityBirmingham, United StatesSee the location
Suspended
Unknown FacilityMobile, United States
Suspended
Unknown FacilitySan Francisco, United States
Suspended
Unknown FacilityColorado Springs, United States

Completed22 Study Centers