Axial SpondyloarthritisPhase 3NCT01808118
Continuing Versus Withdrawing Adalimumab in Maintaining Remission in Non-Radiographic Axial Spondyloarthritis
A Phase 3 study testing adalimumab in people with Axial Spondyloarthritis, run by AbbVie.
Trial summary
The objective of this multicenter, randomized, double-blind study was to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week SC in maintaining remission in subjects with moderate to severe non-radiographic axial spondyloarthritis. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Axial Spondyloarthritis
- What is being tested?
- adalimumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 673 participants
- Where
- No sites listed yet
- Study dates
- 16 Apr 2013to 14 Apr 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult participants with inadequate response to ≥2 nonsteroidal anti-inflammatory drugs (NSAIDs)
- Participants with non-radiographic axial spondyloarthritis fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axial SpA classification criteria, but not fulfilling the radiologic criterion of the modified New York criteria for ankylosing spondylitis
- Participants must have baseline disease activity as defined by having an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.100, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and Patient's Assessment of Total Back Pain score ≥ 4 based on a Numeric Rating Scale (NRS) at both the screening and baseline visits
- Participants with evidence of active inflammation in the sacroiliac (SI) joints or spine on MRI, or elevated high sensitivity C-reactive protein (hs-CRP) at screening
- Negative tuberculosis (TB) screening assessment
- Ability to administer subcutaneous injections or have a qualified person available to administer injections
- If female, either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or of childbearing potential and practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug.
- Participant judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray, and a 12-lead electrocardiogram performed at screening
Who cannot join
- Prior anti-Tumor Necrosis Factor (TNF) therapy; biologic therapy with a potential therapeutic impact on SpA or treated with an investigational drug of chemical or biologic nature within 30 days or 5 half-lives prior to the baseline visit.
- Fulfillment of the radiologic criterion of the modified New York criteria for Ankylosing Spondylitis at or prior to the screening visit
- Recent infection requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the baseline visit or oral anti-infectives within 14 days prior to the baseline visit
- Significant medical events or conditions that may put participants at risk for participation
- Female participants who are pregnant or breast-feeding or considering becoming pregnant during the study
- Known hypersensitivity to adalimumab or its excipients as stated in the label
About this study
Official title: A Multicenter, Randomized, Double-Blind, Study Comparing the Efficacy and Safety of Continuing Versus Withdrawing Adalimumab Therapy in Maintaining Remission in Subjects With Non-Radiographic Axial Spondyloarthritis
The objective of this multicenter, randomized, double-blind study was to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week SC in maintaining remission in subjects with moderate to severe non-radiographic axial spondyloarthritis.
Read the detailed description
The study duration included a 42-day Screening Period, a 28-week open-label 40 mg adalimumab every other week (eow) treatment period (Period 1), a 40-week double-blind placebo controlled eow treatment period (Period 2) with an opportunity to receive at least 12 weeks of rescue therapy with open-label adalimumab (participants that flared at Weeks 60, 64 or 68 were allowed 12 weeks of rescue therapy and final visits were at Weeks 72, 76 or 80 respectively), plus a 70-day follow-up phone call. Participants in sustained Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were randomized at Week 28 at a 1:1 ratio to receive either blinded adalimumab 40 mg eow or matching placebo. The length of exposure to adalimumab depended on remission or flare status and ranged from 20 (first time Ankylosing Spondylitis Disease Activity Score [ASDAS] remission was calculated) to 80 weeks of treatment.
- Conditions
- Axial Spondyloarthritis
- Being tested
- adalimumab, Placebo
- Keywords
- Spondylitis, Spondylarthropathy, Ankylosing Spondyloarthritis, Spondyloarthritis, Spinal Diseases, Musculoskeletal Diseases, Arthritis, Joint Diseases, Adalimumab, Antirheumatic Agents, Anti-Inflammatory Agents
- Medical subject headings
- Axial Spondyloarthritis, Spondylitis, Spondylarthropathies, Spondylitis, Ankylosing, Spondylarthritis, Spinal Diseases, Musculoskeletal Diseases, Arthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adalimumabBiological
Also called Humira, ABT-D2E7
40 mg every other week
PlaceboBiological
every other week
| Study group | Role | What they receive |
|---|---|---|
| Double-Blind Adalimumab | Experimental | 40 mg every other week (eow), Weeks 28-68. Blinded adalimumab was discontinued in participants who met the criteria for flare. Receives: Biological: adalimumab |
| Open-label (OL) Adalimumab | Experimental | 40 mg every other week (eow), Weeks 0-28. If participants flared during the double-blind period, they had an opportunity to receive at least 12 weeks of open-label adalimumab 40 mg eow. Receives: Biological: adalimumab |
| Placebo | Placebo comparator | Placebo every other week (eow), Weeks 28-68. Placebo was discontinued in participants who met the criteria for flare. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
Measured: From Week 28 through 68
Secondary outcomes (22)
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Inactive Disease is defined as a score of <1.300.
Measured: Rescue Therapy Week 12
Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Major Improvement is defined as a change from baseline ≤ -2.000.
Measured: Baseline and Rescue Therapy Week 12
Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Clinically Important Improvement is defined as a change from baseline ≤ -1.100.
Measured: Baseline and Rescue Therapy Week 12
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy
ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain:
- Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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).
Measured: Baseline and Rescue Therapy Week 12
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy
ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain:
- Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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).
Measured: Baseline and Rescue Therapy Week 12
Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy
An Assessment of Spondyloarthritis International Society (ASAS) 5/6 response is a 20% improvement in 5 out of the following 6 domains:
- Patient's Global Assessment of disease activity, on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which assesses participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation: the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none) to 10 (very severe/2 hrs or more duration);
- Spinal mobility: the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility);
- High-sensitivity C-reactive protein level (lower levels = less inflammation).
Measured: Baseline and Rescue Therapy Week 12
Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy
Assessment in SpondyloArthritis International Society (ASAS) partial remission is defined as an absolute score of < 2 units on a 0 to 10 scale for each of the four following domains:
- Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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).
Measured: Rescue Therapy Week 12
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy
The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale [NRS]) 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. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from baseline in BASDAI score.
Measured: Baseline and Rescue Therapy Week 12
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy
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 (very severe, high-dependency disability). Negative mean changes from baseline in the overall score indicate improvement.
Measured: Baseline and Rescue Therapy Week 12
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Inactive Disease is defined as a score of <1.300.
Measured: Weeks 28 and 68
Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Major Improvement is defined as a change from baseline ≤ -2.000.
Measured: Baseline, Weeks 28 and 68
Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). ASDAS Clinically Important Improvement is defined as a change from baseline ≤ -1.100.
Measured: Baseline, Weeks 28 and 68
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68
ASAS20 response was defined as improvement of ≥ 20% relative to baseline and absolute improvement of ≥ 1 unit (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration (defined as a worsening of ≥ 20% and a net worsening of ≥ 1 unit) in the potential remaining domain:
- Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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).
Measured: Baseline, Weeks 28 and 68
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68
ASAS40 response was defined as improvement of ≥ 40% relative to baseline and absolute improvement of ≥ 2 units (on a scale from 0 to 10) in ≥ 3 of the following 4 domains with no deterioration in the potential remaining domain:
- Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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).
Measured: Baseline, Weeks 28 and 68
Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68
An Assessment of Spondyloarthritis International Society (ASAS) 5/6 response is a 20% improvement in 5 out of the following 6 domains:
- Patient's Global Assessment of disease activity, on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which assesses participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation: the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS scores (items 5 [level of stiffness] and 6 [duration of stiffness]) each on a scale from 0 (none) to 10 (very severe/2 hrs or more duration);
- Spinal mobility: the lateral lumbar flexion score of the Bath AS Metrology Index (BASMI) on a scale from 0 (best mobility) to 10 (worst mobility);
- High-sensitivity C-reactive protein level (lower levels = less inflammation).
Measured: Baseline, Weeks 28 and 68
Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68
Assessment in SpondyloArthritis International Society (ASAS) partial remission is defined as an absolute score of < 2 units on a 0 to 10 scale for each of the four following domains:
- Patient's Global Assessment of disease activity, measured on a numeric rating scale (NRS) from 0 (none) to 10 (severe);
- Pain, measured by the total back pain NRS from 0 (no pain) to 10 (most severe);
- Function, measured by the Bath Ankylosing Spondylitis Functional Index (BASFI) which consists of 10 items assessing participants' ability to perform activities on an NRS ranging from 0 (easy) to 10 (impossible);
- Inflammation, measured by the mean of the 2 morning stiffness-related Bath AS Disease Activity Index (BASDAI) NRS 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).
Measured: Baseline, Weeks 28 and 68
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68
The Bath Ankylosing Spondylitis (AS) Disease Activity Index assesses disease activity by asking the participant to answer 6 questions (each on a 10 point numeric rating scale [NRS]) 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. Lower scores indicate less disease activity. BASDAI50 is a 50% improvement from baseline in BASDAI score.
Measured: Baseline, Weeks 28 and 68
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68
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 (very severe, high-dependency disability). Negative mean changes from baseline in the overall score indicate improvement.
Measured: Baseline, Weeks 28 and 68
Time to Flare at Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
Measured: From Week 28 through 68
Time to Partial Flare at Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A partial flare was defined as having any 2 consecutive study visits with ASDAS ≥ 1.300 but <2.100.
Measured: From Week 28 through 68
Number of Participants Reaching Flare Definition by Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
Measured: From Week 28 through 68
Number of Participants Reaching Partial Flare Definition by Week 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A partial flare was defined as having any 2 consecutive study visits with ASDAS ≥ 1.300 but <2.100.
Measured: From Week 28 through 68
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2013 (estimated)
- Study start16 Apr 2013
- Primary completion21 Feb 2017
- Study completion14 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Axial SpondyloarthritisStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 673 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- AbbVie Inc., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01808118
- Sponsor's protocol ID
- M13-375
- Other IDs
- 2012-000646-35
- Status last verified
- Apr 2018
- First submitted
- 7 Mar 2013
- Last updated
- 30 May 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Landewe R, Sieper J, Mease P, Inman RD, Lambert RG, Deodhar A, Marzo-Ortega H, Magrey M, Kiltz U, Wang X, Li M, Zhong S, Mostafa NM, Lertratanakul A, Pangan AL, Anderson JK. Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 2018 Jul 14;392(10142):134-144. doi: 10.1016/S0140-6736(18)31362-X. Epub 2018 Jun 29.
PubMed 29961640
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Study Comparing the Efficacy and Safety of Continuing Versus Withdrawing Adalimumab Therapy in Maintaining Remission in Subjects With Non-Radiographic Axial Spondyloarthritis
- ClinicalTrials.gov ID
- NCT01808118
- Acronym / sponsor ID
- M13-375
- Conditions
- Axial Spondyloarthritis
- Keywords
- Spondylitis, Spondylarthropathy, Ankylosing Spondyloarthritis, Spondyloarthritis, Spinal Diseases, Musculoskeletal Diseases, Arthritis, Joint Diseases
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 673 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 16 Apr 2013 (actual)
- Primary completion
- 21 Feb 2017 (actual)
- Study completion
- 14 Apr 2017 (actual)
- First posted
- 11 Mar 2013 (estimated)
- Results
- Posted 30 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this multicenter, randomized, double-blind study was to evaluate the efficacy and safety of continuing versus withdrawing therapy with adalimumab 40 mg given every other week SC in maintaining remission in subjects with moderate to severe non-radiographic axial spondyloarthritis.
Detailed description
The study duration included a 42-day Screening Period, a 28-week open-label 40 mg adalimumab every other week (eow) treatment period (Period 1), a 40-week double-blind placebo controlled eow treatment period (Period 2) with an opportunity to receive at least 12 weeks of rescue therapy with open-label adalimumab (participants that flared at Weeks 60, 64 or 68 were allowed 12 weeks of rescue therapy and final visits were at Weeks 72, 76 or 80 respectively), plus a 70-day follow-up phone call. Participants in sustained Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease were randomized at Week 28 at a 1:1 ratio to receive either blinded adalimumab 40 mg eow or matching placebo. The length of exposure to adalimumab depended on remission or flare status and ranged from 20 (first time Ankylosing Spondylitis Disease Activity Score [ASDAS] remission was calculated) to 80 weeks of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Double-Blind Adalimumab | Experimental | Biological: adalimumab40 mg every other week (eow), Weeks 28-68. Blinded adalimumab was discontinued in participants who met the criteria for flare. |
| Open-label (OL) Adalimumab | Experimental | Biological: adalimumab40 mg every other week (eow), Weeks 0-28. If participants flared during the double-blind period, they had an opportunity to receive at least 12 weeks of open-label adalimumab 40 mg eow. |
| Placebo | Placebo comparator | Biological: PlaceboPlacebo every other week (eow), Weeks 28-68. Placebo was discontinued in participants who met the criteria for flare. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult participants with inadequate response to ≥2 nonsteroidal anti-inflammatory drugs (NSAIDs)
- Participants with non-radiographic axial spondyloarthritis fulfilling the Assessment of Spondyloarthritis International Society (ASAS) axial SpA classification criteria, but not fulfilling the radiologic criterion of the modified New York criteria for ankylosing spondylitis
- Participants must have baseline disease activity as defined by having an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥ 2.100, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 and Patient's Assessment of Total Back Pain score ≥ 4 based on a Numeric Rating Scale (NRS) at both the screening and baseline visits
- Participants with evidence of active inflammation in the sacroiliac (SI) joints or spine on MRI, or elevated high sensitivity C-reactive protein (hs-CRP) at screening
- Negative tuberculosis (TB) screening assessment
Key exclusion criteria (6 listed)
- Prior anti-Tumor Necrosis Factor (TNF) therapy; biologic therapy with a potential therapeutic impact on SpA or treated with an investigational drug of chemical or biologic nature within 30 days or 5 half-lives prior to the baseline visit.
- Fulfillment of the radiologic criterion of the modified New York criteria for Ankylosing Spondylitis at or prior to the screening visit
- Recent infection requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the baseline visit or oral anti-infectives within 14 days prior to the baseline visit
- Significant medical events or conditions that may put participants at risk for participation
- Female participants who are pregnant or breast-feeding or considering becoming pregnant during the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adalimumabAlso: Humira, ABT-D2E740 mg every other week | Biological | Double-Blind Adalimumab, Open-label (OL) Adalimumab |
| Placeboevery other week | Biological | Placebo |
Primary outcome
Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68
Time frame: From Week 28 through 68
The Ankylosing Spondylitis Disease Activity Score (ASDAS) tool is a self-administered questionnaire/objective laboratory evaluation. The questionnaire assesses disease activity, back pain, and peripheral pain/swelling on a numeric rating scale (from 0 (normal) to 10 (very severe)) and duration of morning stiffness on a numeric rating scale (from 0 to 10, with 0 being none and 10 representing a duration of ≥2 hours). The laboratory parameter is a measurement of high-sensitivity C-reactive protein (mg/L) (hs-CRP). Data from five variables (disease activity, back pain, duration of morning stiffness, peripheral pain/swelling, and hs-CRP) are combined to yield a score (0 to no defined upper limit). During Period 2 participants visited study sites at Weeks 28, 32, 36, 40, 44, 48, 52, 56, 60, 64 and 68 or if they discontinued early from the study. A flare was defined as having any 2 consecutive study visits with ASDAS ≥ 2.100.
22 secondary outcomes
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at 12 Weeks After Initiation of Rescue Therapy
Time frame: Rescue Therapy Week 12
Number of Participants Achieving ASDAS Major Improvement at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Number of Participants Achieving ASDAS Clinically Important Improvement at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Number of Participants Achieving an ASAS 5/6 Response at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Number of Participants Achieving ASAS Partial Remission at 12 Weeks After Initiation of Rescue Therapy
Time frame: Rescue Therapy Week 12
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at 12 Weeks After Initiation of Rescue Therapy
Time frame: Baseline and Rescue Therapy Week 12
Number of Participants With Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive Disease at Weeks 28 and 68
Time frame: Weeks 28 and 68
Number of Participants Achieving ASDAS Major Improvement at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Number of Participants Achieving ASDAS Clinically Important Improvement at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 Response at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Number of Participants Achieving an Assessment of Spondyloarthritis International Society (ASAS) 40 Response at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Number of Participants Achieving an ASAS 5/6 Response at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Number of Participants Achieving ASAS Partial Remission at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Number of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 Response at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Change From Baseline in Disability Index of Health Assessment Questionnaire Modified for the Spondyloarthropathies (HAQ-S) at Weeks 28 and 68
Time frame: Baseline, Weeks 28 and 68
Time to Flare at Week 68
Time frame: From Week 28 through 68
Time to Partial Flare at Week 68
Time frame: From Week 28 through 68
Number of Participants Reaching Flare Definition by Week 68
Time frame: From Week 28 through 68
Number of Participants Reaching Partial Flare Definition by Week 68
Time frame: From Week 28 through 68
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29961640Landewe R, Sieper J, Mease P, Inman RD, Lambert RG, Deodhar A, Marzo-Ortega H, Magrey M, Kiltz U, Wang X, Li M, Zhong S, Mostafa NM, Lertratanakul A, Pangan AL, Anderson JK. Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study. Lancet. 2018 Jul 14;392(10142):134-144. doi: 10.1016/S0140-6736(18)31362-X. Epub 2018 Jun 29.
- Humira Prescribing InformationLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Axial Spondyloarthritis
Active, not recruiting
Effects of Resistance Exercise on Enthesitis in Patients With Spondyloarthritis
Spondyloarthritis (SpA), Axial Spondylarthritis (axSpA)
RecruitingPhase 1
A Study of HB0017 Injection in Healthy Volunteers to Evaluate Safety and Tolerability of a Single Subcutaneous Injection in Low-Body-Weight Subjects; and Pharmacokinetics at Different Subcutaneous Injection Sites at the Same Dose
Psoriasis, Ankylosing Spondylitis
RecruitingPhase 1
A Study to Learn if Bimekizumab Given in Different Ways is Safe and Moves Similarly Throughout the Body Over Time in Adults
Psoriatic Arthritis, Axial Spondyloarthritis
RecruitingObservational study
Pain Phenotyping of Rheumatic Diseases - An Observational Study
Rheumatic Diseases, Lupus Erythematosus, Systemic
RecruitingObservational study
Identification of Serum Level of Glutathione Peroxidase 4
Spondyloarthropathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
AbbVie Inc. study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing adalimumab in people with Axial Spondyloarthritis, run by AbbVie.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 May 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Did Not Experience a Flare During Period 2 by Week 68 (time frame: From Week 28 through 68). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01808118, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2018.