search
Back to results

Dose-Ranging Study Of Tofacitinib In Adults With Active Ankylosing Spondylitis

Primary Purpose

Ankylosing Spondylitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tofacitinib 2 mg
Tofacitinib 5 mg
Tofacitinib 10 mg
Placebo
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ankylosing Spondylitis focused on measuring Ankylosing Spondylitis, Spondylitis, Ankylosing, Spondyloarthritis, Spondyloarthropathy, Oral preparation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Documented diagnosis of Ankylosing Spondylitis
  • Has active disease despite concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) treatment or is intolerant to NSAIDs

Exclusion Criteria:

  • Pregnant or lactating females
  • Currently receiving or previous use of a Tumor Necrosis Factor (TNF) inhibitor or any biological agent

Sites / Locations

  • Desert Medical Imaging
  • Desert Medical Advances
  • Arthritis & Rheumatology Associates
  • Millennium Research
  • Southwest Florida Clinical Research Center
  • Covance Central Laboratory Services,Inc
  • Klein & Associates, M.D., P.A.
  • Progressive Radiology
  • Advanced Medical Imaging (MRI center)
  • Arthritis Center of Nebraska (X-ray center)
  • Physician Research Collaboration, LLC
  • Charlotte Radiology/ Carolina Imaging Services
  • Joint and Muscle Research Institute
  • Presbyterian Imaging
  • Paramount Medical Research & Consulting, LLC
  • Premier Physicians Centers
  • Oregon Health & Science University
  • Altoona Center for Clinical Research
  • Clinical Research Center of Reading, LLC
  • Investigational Drug Service
  • Seattle Rheumatology Associates
  • Arthritis Northwest, PLLC
  • Institut de Rhumatologie de Montreal
  • G.R.M.O. Inc
  • Artroscan s.r.o.
  • Mediscan Group s.r.o.
  • Revmatologicky ustav
  • Revmatologicka ambulance
  • Medical Plus
  • Charité Universitaetsmedizin Berlin
  • Praxis fuer klinische Studien
  • Gemeinschaftspraxis Dres. von Hinueber / Demary
  • Immunologisches Zentrum Vogelsang-Gommern GmbH
  • Orszagos Reumatologiai es Fiziotherapias Intezet II. Reumatologiai Osztaly
  • Qualiclinic Kft
  • Synexus Magyarorszag Kft. - Synexus Hungary Clinical Research Centre
  • Dr. Rethy Pál Korhaz es Rendelointezet, Reumatologia
  • Debreceni Egyetem Orvos- és Egészségtudományi Centrum
  • CRU Hungary Kft.
  • Csolnoky Ferenc Korhaz Reumatologiai Osztaly
  • Chonnam National University Hospital
  • INHA University Hospital
  • Seoul National University Hospital
  • Ajou University Hospital
  • NZOZ Lecznica MAK-MED s.c.
  • Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych
  • Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy
  • Centrum Kliniczno-Badawcze J. Brzezicki, B. Gornikiewicz-Brzezicka Lekarze Spolka Partnerska
  • Medica Pro Familia Sp. z o.o. S.K.A. Oddzial Katowice
  • Malopolskie Centrum Medyczne S.C.
  • Zespol Poradni Specjalistycznych Reumed Filia Onyksowa
  • Twoja Przychodnia - Centrum Medyczne Nowa Sol
  • NZOZ Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna w Toruniu
  • SBEI HPE Ural State Medical University of MoH of RF based on Municipal Budgetary Institution
  • Federal State Budgetary Institution
  • OOO AVA-PETER "Scandinavia clinic"
  • Saint-Petersburg State Budgetary Healthcare Institution
  • Hospital Clinico Universitario Santiago de Compostela
  • Hospital Universitari de Bellvitge
  • Hospital Universitario Marques de Valdecilla
  • Complexo Hospitalario Universitario A Coruna
  • Hospital Universitario Reina Sofia
  • Hospital Universitario De La Paz
  • Corporacio Sanitaria Parc Tauli
  • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Chung Shan Medical University Hospital
  • China medical university hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Tofacitinib 2 mg

Tofacitinib 5 mg

Tofacitinib 10 mg

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 12
The primary analysis of this outcome measure was performed using the Emax model. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of greater than or equal to (≥) 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and less than or equal to (≤)1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by nonresponsive (NRI)/ last observation carried forward (LOCF). Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.
Percentage of Participants Achieving ASAS20 at Week 12
The supportive analysis of this outcome measure was performed using the normal approximation for two proportions. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by NRI/LOCF. Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.

Secondary Outcome Measures

Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8
Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by NRI/LOCF. Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score of the Sacroiliac (SI) Joints at Week 12
SPARCC scoring consists of assessing six SI joint MRI image coronal slices representing the largest proportion of the synovial compartment of the SI joints for edema. The maximum score per slice was 2 and 12 for all 6 slices. The total minimum and maximum score for all SI joints across 6 slices is 0 to 72 and higher scores indicate more inflammation. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Change From Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12
SPARCC scoring of the magnetic resonance imaging (MRI) of the spine consists of assessing six disco-vertebral units (DVU) with 3 consecutive sagittal slices at each DVU. The minimum and maximum SPARCC score for all 6 DVUs is 0 to 108, with higher scores indicating more damage. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Change From Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12
Berlin modification of the ASspiMRI is a measure of acute lesion as determined by short-tau inversion recovery (STIR) sequences. All 23 disco-vertebral units (DVU) of the spine (from C2 to S1), defined as the region between 2 virtual lines through the middle of each vertebra, were scored in a single dimension, which is represented the highest level of inflammation in that particular DVU. Total spine ASspiMRI scores can range from 0-69 with higher scores indicating more disease activity. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Percentage of Participants Achieving 40% Improvement in ASAS Score at Weeks 2, 4, 8 and 12
ASAS 40 is defined as ≥40% and absolute change of ≥2 units in at least 3 domains on a 0-10 scale (0=no disease activity, 10=high disease activity), and no worsening in the remaining domain. Missing data were handled by NRI/LOCF.
Percentage of Participants Achieving ASAS5/6 Response at Weeks 2, 4, 8 and 12
ASAS5/6 consists of 6 domains: the 4 used in ASAS20 (Patient's Global Assessment of Disease Activity, spinal pain, function, inflammation plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). ASAS 5/6 is defined as ≥20% improvement in at least 5 domains and no worsening in the remaining domain. Missing data were handled by NRI/LOCF.
Change From Baseline of Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein ASDAS(CRP) at Weeks 2, 4, 8 and 12
The ASDAS(CRP) is a derived score that uses back pain, duration of morning stiffness, Patient's Global Assessment of their disease and peripheral pain/swelling. The formula used for calculating the ASDAS (CRP)is: 0.12 x Back Pain + 0.06 x Duration of Morning Stiffness + 0.11 x Patient Global + 0.07 x Peripheral Pain/Swelling + 0.58 x Ln(CRP+1). The calculated score can be from 0 to no defined upper limit. A negative number indicates a reduction in the score which indicates decrease in disease activity.
Percentage of Participants With ASDAS Clinically Important Improvement at Weeks 2, 4, 8 and 12
The ASDAS clinically important improvement was calculated from the ASDAS data. The ASDAS clinically important improvement is defined as change (decrease) from baseline of ≥1.1 units. Missing data were handled by NRI/LOCF.
Percentage of Participants With ASDAS Major Improvement at Weeks 2, 4, 8 and 12
The ASDAS major improvement was calculated from the ASDAS data. The ASDAS major improvement was defined as change (decrease) from baseline of ≥2.0 units. Missing data were handled by NRI/LOCF.
Percentage of Participants Achieving ASDAS Inactive Disease at Weeks 2, 4, 8 and 12
The ASDAS inactive disease was calculated from the ASDAS data. The ASDAS inactive disease was defined as ASDAS <1.3 units. Missing data were handled by NRI/LOCF.
Change From Baseline in BASDAI Total Score at Week 2, 4, 8 and 12
BASDAI is a validated self-assessment tool used to determine disease activity in participant with Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q)1-4. This score is then divided by 5. BASDAI=Q1+Q2+Q3+Q4+[Q5+Q6/2]/5. The final BASDAI score averages the individual assessments for a final score range of 0-10. Negative values indicate improvement.
Percentage of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 Response at Weeks 2, 4, 8 and 12
BASDAI is a validated self-assessment tool used to determine disease activity in participant with Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q)1-4. This score is then divided by 5. The final BASDAI score range from 0-10. A positive response was defined as a 50% improvement in the BASDAI from baseline.
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8 and 12
BASFI is a validated self-assessment tool that determines the degree of physical functional limitation in Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0=easy, 10=impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions with lower scores indicating better physical function. The higher the negative value the better the improvement.
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8 and 12
BASMI is an objective measure of spinal mobility and was completed by a blinded assessor. The BASMI score is composed of 5 clinical measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. The derived score used the average of the 5 assessments on a scale of 0-10 scale with higher scores indicating more impairment of spinal mobility. BASMI was analyzed using the linear function method. The higher the negative value the better the improvement.
Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8 and 12
Assessment of enthesitis of 13 sites was performed in the following, 1st costochondral joint left and right, 7th costochondral joint left and right, posterior superior iliac spine left and right, anterior superior iliac spine left and right, iliac crest left and right, 5th lumbar spinous process and proximal insertion of Achilles tendon left and right. Each site was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness).
Extra-Articular Involvement From Specific Ankylosing Spondylitis Medical History
Participants were assessed at Baseline, Week 12 and Week 16 (Follow-up) to determine if they had specific Ankylosing Spondylitis medical history or changes in specific Ankylosing Spondylitis medical history which included: Inflammatory Bowel Disease (IBD), Peripheral Articular Involvement (PAI; as assessed by swollen joint count), psoriasis (PSO) and uveitis (UVE).
Change From Baseline of Total Swollen Joint Count at Weeks 2, 4 8 and 12
This assessment was performed by the blinded assessor using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints) for determination of the total number of swollen joints. Forty-four joints were assessed for swelling on left and right side and included the following: sternoclaviculars, acromioclaviculars, shoulders, elbows, wrists, metacarpophalangeals (I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (II, III, IV, V), knees, ankles, and metatarsophalangeals (I, II, III, IV, V). Artificial joints were not assessed. A negative change means improvement.
Change From Baseline of Mean Spinal Mobility (Chest Expansion) at Week 2, 4, 8 and 12
Chest expansion, measured in centimeters (cm), is defined as the difference in the thoracic circumference during full expiration versus full inspiration. This was measured at the 4th intercostal space. The difference between maximal inspiration and expiration of the two attempts was recorded. The better of the two attempts was used to calculate chest expansion. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Change From Baseline to Week 12 in Short-Form-36 Health Survey (SF-36) Physical and Mental Health Scores at Week 12
SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=no functioning, 100=highest level of functioning). Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Change From Baseline in EuroQol EQ-5D Health State Profile (EQ-5D) Utility Score at Week 12
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of single utility score. Health state profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression; Scale range 1 to 3 (1=better health state [no problems], 3=worst health state [confined to bed]).
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 2, 4, 8 and 12
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).

Full Information

First Posted
February 6, 2013
Last Updated
May 4, 2016
Sponsor
Pfizer
search

1. Study Identification

Unique Protocol Identification Number
NCT01786668
Brief Title
Dose-Ranging Study Of Tofacitinib In Adults With Active Ankylosing Spondylitis
Official Title
A Phase 2, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study Of The Efficacy And Safety Of Tofacitinib In Subjects With Active Ankylosing Spondylitis (as)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This is the first study of oral tofacitinib in adults with active ankylosing spondylitis. It is designed to obtain information on the efficacy and safety of 3 different doses of tofacitinib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ankylosing Spondylitis
Keywords
Ankylosing Spondylitis, Spondylitis, Ankylosing, Spondyloarthritis, Spondyloarthropathy, Oral preparation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
208 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tofacitinib 2 mg
Arm Type
Experimental
Arm Title
Tofacitinib 5 mg
Arm Type
Experimental
Arm Title
Tofacitinib 10 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Tofacitinib 2 mg
Intervention Description
4 blinded tablets (two 1 mg tablets of tofacitinib along with two 5 mg matching placebo tablets) will be administered orally twice a day (in the AM and PM) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Tofacitinib 5 mg
Intervention Description
4 blinded tablets (one 5 mg tablet of tofacitinib, one 5 mg and two 1 mg matching placebo tablets) will be administered orally twice a day (in the AM and PM) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Tofacitinib 10 mg
Intervention Description
4 blinded tablets (two 5 mg tablets of tofacitinib and two 1 mg matching placebo tablets) will be administered orally twice a day (in the AM and PM) for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
4 blinded tablets (two 1 mg and two 5 mg matching placebo tablets) will be administered orally twice a day (in the AM and PM) for 12 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving 20 Percent (%) Improvement in Assessment of SpondyloArthritis International Society (ASAS) Score (ASAS 20) at Week 12
Description
The primary analysis of this outcome measure was performed using the Emax model. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of greater than or equal to (≥) 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and less than or equal to (≤)1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by nonresponsive (NRI)/ last observation carried forward (LOCF). Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.
Time Frame
Week 12
Title
Percentage of Participants Achieving ASAS20 at Week 12
Description
The supportive analysis of this outcome measure was performed using the normal approximation for two proportions. Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by NRI/LOCF. Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8
Description
Clinical response to treatment was assessed according to ASAS20 criteria. ASAS20 responder had improvement of ≥ 20% and ≥1 unit in at least 3 domains (on a scale of 0 [least] to 10 [worst]) and no worsening of ≥20% and ≤1 unit in the remaining domain. The domains are: Patient's Global Assessment of Disease Activity, spinal pain, function and inflammation (from Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]). Missing data were handled by NRI/LOCF. Missing values due to a subject dropping out from the study were handled by setting the ASAS20 value to NRI. The LOCF approach was applied to missing components, if just some of the components of the ASAS20 were missing.
Time Frame
Baseline, Week 2, Week 4, Week 8
Title
Change From Baseline in Spondyloarthritis Research Consortium of Canada (SPARCC) Magnetic Resonance Imaging (MRI) Index of Disease Activity Score of the Sacroiliac (SI) Joints at Week 12
Description
SPARCC scoring consists of assessing six SI joint MRI image coronal slices representing the largest proportion of the synovial compartment of the SI joints for edema. The maximum score per slice was 2 and 12 for all 6 slices. The total minimum and maximum score for all SI joints across 6 slices is 0 to 72 and higher scores indicate more inflammation. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Time Frame
Baseline, Week 12
Title
Change From Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12
Description
SPARCC scoring of the magnetic resonance imaging (MRI) of the spine consists of assessing six disco-vertebral units (DVU) with 3 consecutive sagittal slices at each DVU. The minimum and maximum SPARCC score for all 6 DVUs is 0 to 108, with higher scores indicating more damage. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12
Description
Berlin modification of the ASspiMRI is a measure of acute lesion as determined by short-tau inversion recovery (STIR) sequences. All 23 disco-vertebral units (DVU) of the spine (from C2 to S1), defined as the region between 2 virtual lines through the middle of each vertebra, were scored in a single dimension, which is represented the highest level of inflammation in that particular DVU. Total spine ASspiMRI scores can range from 0-69 with higher scores indicating more disease activity. A negative change from baseline indicates improvement. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Time Frame
Baseline, Week 12
Title
Percentage of Participants Achieving 40% Improvement in ASAS Score at Weeks 2, 4, 8 and 12
Description
ASAS 40 is defined as ≥40% and absolute change of ≥2 units in at least 3 domains on a 0-10 scale (0=no disease activity, 10=high disease activity), and no worsening in the remaining domain. Missing data were handled by NRI/LOCF.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Percentage of Participants Achieving ASAS5/6 Response at Weeks 2, 4, 8 and 12
Description
ASAS5/6 consists of 6 domains: the 4 used in ASAS20 (Patient's Global Assessment of Disease Activity, spinal pain, function, inflammation plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). ASAS 5/6 is defined as ≥20% improvement in at least 5 domains and no worsening in the remaining domain. Missing data were handled by NRI/LOCF.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline of Ankylosing Spondylitis Disease Activity Score Using C-Reactive Protein ASDAS(CRP) at Weeks 2, 4, 8 and 12
Description
The ASDAS(CRP) is a derived score that uses back pain, duration of morning stiffness, Patient's Global Assessment of their disease and peripheral pain/swelling. The formula used for calculating the ASDAS (CRP)is: 0.12 x Back Pain + 0.06 x Duration of Morning Stiffness + 0.11 x Patient Global + 0.07 x Peripheral Pain/Swelling + 0.58 x Ln(CRP+1). The calculated score can be from 0 to no defined upper limit. A negative number indicates a reduction in the score which indicates decrease in disease activity.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Percentage of Participants With ASDAS Clinically Important Improvement at Weeks 2, 4, 8 and 12
Description
The ASDAS clinically important improvement was calculated from the ASDAS data. The ASDAS clinically important improvement is defined as change (decrease) from baseline of ≥1.1 units. Missing data were handled by NRI/LOCF.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Percentage of Participants With ASDAS Major Improvement at Weeks 2, 4, 8 and 12
Description
The ASDAS major improvement was calculated from the ASDAS data. The ASDAS major improvement was defined as change (decrease) from baseline of ≥2.0 units. Missing data were handled by NRI/LOCF.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Percentage of Participants Achieving ASDAS Inactive Disease at Weeks 2, 4, 8 and 12
Description
The ASDAS inactive disease was calculated from the ASDAS data. The ASDAS inactive disease was defined as ASDAS <1.3 units. Missing data were handled by NRI/LOCF.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline in BASDAI Total Score at Week 2, 4, 8 and 12
Description
BASDAI is a validated self-assessment tool used to determine disease activity in participant with Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q)1-4. This score is then divided by 5. BASDAI=Q1+Q2+Q3+Q4+[Q5+Q6/2]/5. The final BASDAI score averages the individual assessments for a final score range of 0-10. Negative values indicate improvement.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Percentage of Participants Achieving a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 Response at Weeks 2, 4, 8 and 12
Description
BASDAI is a validated self-assessment tool used to determine disease activity in participant with Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0 = none and 10 = very severe) participant's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI score is calculated by computing the mean of questions 5 and 6 and adding it to the sum of questions (Q)1-4. This score is then divided by 5. The final BASDAI score range from 0-10. A positive response was defined as a 50% improvement in the BASDAI from baseline.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) at Weeks 2, 4, 8 and 12
Description
BASFI is a validated self-assessment tool that determines the degree of physical functional limitation in Ankylosing Spondylitis. Utilizing a Numerical Rating Scale (NRS) of 0-10 (0=easy, 10=impossible), participants answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions with lower scores indicating better physical function. The higher the negative value the better the improvement.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline in Bath Ankylosing Spondylitis Metrology Index (BASMI) at Weeks 2, 4, 8 and 12
Description
BASMI is an objective measure of spinal mobility and was completed by a blinded assessor. The BASMI score is composed of 5 clinical measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. The derived score used the average of the 5 assessments on a scale of 0-10 scale with higher scores indicating more impairment of spinal mobility. BASMI was analyzed using the linear function method. The higher the negative value the better the improvement.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline in Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) at Weeks 4, 8 and 12
Description
Assessment of enthesitis of 13 sites was performed in the following, 1st costochondral joint left and right, 7th costochondral joint left and right, posterior superior iliac spine left and right, anterior superior iliac spine left and right, iliac crest left and right, 5th lumbar spinous process and proximal insertion of Achilles tendon left and right. Each site was graded for the presence (1) and absence (0) of tenderness yielding total MASES ranging from 0 (no tenderness) to 13 (worst possible score; severe tenderness).
Time Frame
Baseline, Week 4, Week 8, Week 12
Title
Extra-Articular Involvement From Specific Ankylosing Spondylitis Medical History
Description
Participants were assessed at Baseline, Week 12 and Week 16 (Follow-up) to determine if they had specific Ankylosing Spondylitis medical history or changes in specific Ankylosing Spondylitis medical history which included: Inflammatory Bowel Disease (IBD), Peripheral Articular Involvement (PAI; as assessed by swollen joint count), psoriasis (PSO) and uveitis (UVE).
Time Frame
Baseline, Week 12 and Follow-up
Title
Change From Baseline of Total Swollen Joint Count at Weeks 2, 4 8 and 12
Description
This assessment was performed by the blinded assessor using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints) for determination of the total number of swollen joints. Forty-four joints were assessed for swelling on left and right side and included the following: sternoclaviculars, acromioclaviculars, shoulders, elbows, wrists, metacarpophalangeals (I, II, III, IV, V), thumb interphalangeal, proximal interphalangeals (II, III, IV, V), knees, ankles, and metatarsophalangeals (I, II, III, IV, V). Artificial joints were not assessed. A negative change means improvement.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline of Mean Spinal Mobility (Chest Expansion) at Week 2, 4, 8 and 12
Description
Chest expansion, measured in centimeters (cm), is defined as the difference in the thoracic circumference during full expiration versus full inspiration. This was measured at the 4th intercostal space. The difference between maximal inspiration and expiration of the two attempts was recorded. The better of the two attempts was used to calculate chest expansion. Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12
Title
Change From Baseline to Week 12 in Short-Form-36 Health Survey (SF-36) Physical and Mental Health Scores at Week 12
Description
SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (0=no functioning, 100=highest level of functioning). Missing data at Week 12 were imputed by LOCF if data at an early visit (discontinuation visit) were available.
Time Frame
Baseline, Week 12
Title
Change From Baseline in EuroQol EQ-5D Health State Profile (EQ-5D) Utility Score at Week 12
Description
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of single utility score. Health state profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression; Scale range 1 to 3 (1=better health state [no problems], 3=worst health state [confined to bed]).
Time Frame
Baseline, Week 12
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Weeks 2, 4, 8 and 12
Description
FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).
Time Frame
Baseline, Week 2, Week 4, Week 8, Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented diagnosis of Ankylosing Spondylitis Has active disease despite concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) treatment or is intolerant to NSAIDs Exclusion Criteria: Pregnant or lactating females Currently receiving or previous use of a Tumor Necrosis Factor (TNF) inhibitor or any biological agent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Desert Medical Imaging
City
Indian Wells
State/Province
California
ZIP/Postal Code
92210
Country
United States
Facility Name
Desert Medical Advances
City
Palm Desert
State/Province
California
ZIP/Postal Code
92260
Country
United States
Facility Name
Arthritis & Rheumatology Associates
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Millennium Research
City
Ormond Beach
State/Province
Florida
ZIP/Postal Code
32174
Country
United States
Facility Name
Southwest Florida Clinical Research Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609
Country
United States
Facility Name
Covance Central Laboratory Services,Inc
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46214
Country
United States
Facility Name
Klein & Associates, M.D., P.A.
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Progressive Radiology
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Advanced Medical Imaging (MRI center)
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68506
Country
United States
Facility Name
Arthritis Center of Nebraska (X-ray center)
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68516
Country
United States
Facility Name
Physician Research Collaboration, LLC
City
Lincoln
State/Province
Nebraska
ZIP/Postal Code
68516
Country
United States
Facility Name
Charlotte Radiology/ Carolina Imaging Services
City
Ballantyne
State/Province
North Carolina
ZIP/Postal Code
28277
Country
United States
Facility Name
Joint and Muscle Research Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Presbyterian Imaging
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Paramount Medical Research & Consulting, LLC
City
Middleburg Heights
State/Province
Ohio
ZIP/Postal Code
44130
Country
United States
Facility Name
Premier Physicians Centers
City
Westlake
State/Province
Ohio
ZIP/Postal Code
44145
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
Clinical Research Center of Reading, LLC
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Investigational Drug Service
City
Seatle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Seattle Rheumatology Associates
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Arthritis Northwest, PLLC
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Institut de Rhumatologie de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 1S6
Country
Canada
Facility Name
G.R.M.O. Inc
City
Quebec
ZIP/Postal Code
G1V 3M7
Country
Canada
Facility Name
Artroscan s.r.o.
City
Ostrava
ZIP/Postal Code
722 00
Country
Czech Republic
Facility Name
Mediscan Group s.r.o.
City
Praha 11- Chodov
ZIP/Postal Code
14800
Country
Czech Republic
Facility Name
Revmatologicky ustav
City
Praha 2
ZIP/Postal Code
128 50
Country
Czech Republic
Facility Name
Revmatologicka ambulance
City
Praha 4
ZIP/Postal Code
140 00
Country
Czech Republic
Facility Name
Medical Plus
City
Uherske Hradiste
ZIP/Postal Code
68601
Country
Czech Republic
Facility Name
Charité Universitaetsmedizin Berlin
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Praxis fuer klinische Studien
City
Hamburg
ZIP/Postal Code
22415
Country
Germany
Facility Name
Gemeinschaftspraxis Dres. von Hinueber / Demary
City
Hildesheim
ZIP/Postal Code
31134
Country
Germany
Facility Name
Immunologisches Zentrum Vogelsang-Gommern GmbH
City
Vogelsang-Gommern
ZIP/Postal Code
39245
Country
Germany
Facility Name
Orszagos Reumatologiai es Fiziotherapias Intezet II. Reumatologiai Osztaly
City
Budapest
ZIP/Postal Code
1023
Country
Hungary
Facility Name
Qualiclinic Kft
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Synexus Magyarorszag Kft. - Synexus Hungary Clinical Research Centre
City
Budapest
ZIP/Postal Code
1036
Country
Hungary
Facility Name
Dr. Rethy Pál Korhaz es Rendelointezet, Reumatologia
City
Békéscsaba
ZIP/Postal Code
5600
Country
Hungary
Facility Name
Debreceni Egyetem Orvos- és Egészségtudományi Centrum
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Facility Name
CRU Hungary Kft.
City
Szikszó
ZIP/Postal Code
3800
Country
Hungary
Facility Name
Csolnoky Ferenc Korhaz Reumatologiai Osztaly
City
Veszprem
ZIP/Postal Code
H-8200
Country
Hungary
Facility Name
Chonnam National University Hospital
City
Gwangju
ZIP/Postal Code
501-757
Country
Korea, Republic of
Facility Name
INHA University Hospital
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon
ZIP/Postal Code
443-721
Country
Korea, Republic of
Facility Name
NZOZ Lecznica MAK-MED s.c.
City
Nadarzyn
State/Province
Mazowieckie
ZIP/Postal Code
05-830
Country
Poland
Facility Name
Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych
City
Bialystok
ZIP/Postal Code
15- 879
Country
Poland
Facility Name
Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
Centrum Kliniczno-Badawcze J. Brzezicki, B. Gornikiewicz-Brzezicka Lekarze Spolka Partnerska
City
Elblag
ZIP/Postal Code
82-300
Country
Poland
Facility Name
Medica Pro Familia Sp. z o.o. S.K.A. Oddzial Katowice
City
Katowice
ZIP/Postal Code
40-954
Country
Poland
Facility Name
Malopolskie Centrum Medyczne S.C.
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Zespol Poradni Specjalistycznych Reumed Filia Onyksowa
City
Lublin
ZIP/Postal Code
20-582
Country
Poland
Facility Name
Twoja Przychodnia - Centrum Medyczne Nowa Sol
City
Nowa Sol
ZIP/Postal Code
67-100
Country
Poland
Facility Name
NZOZ Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna w Toruniu
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
SBEI HPE Ural State Medical University of MoH of RF based on Municipal Budgetary Institution
City
Ekaterinburg
ZIP/Postal Code
620149
Country
Russian Federation
Facility Name
Federal State Budgetary Institution
City
Moscow
ZIP/Postal Code
115522
Country
Russian Federation
Facility Name
OOO AVA-PETER "Scandinavia clinic"
City
Saint-Petersburg
ZIP/Postal Code
191014
Country
Russian Federation
Facility Name
Saint-Petersburg State Budgetary Healthcare Institution
City
Sestroretsk
ZIP/Postal Code
197706
Country
Russian Federation
Facility Name
Hospital Clinico Universitario Santiago de Compostela
City
Santiago de Compostela
State/Province
A Coruna
ZIP/Postal Code
15706
Country
Spain
Facility Name
Hospital Universitari de Bellvitge
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Hospital Universitario Marques de Valdecilla
City
Santander
State/Province
Cantabria
ZIP/Postal Code
39008
Country
Spain
Facility Name
Complexo Hospitalario Universitario A Coruna
City
A Coruna
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital Universitario Reina Sofia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario De La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Corporacio Sanitaria Parc Tauli
City
Sabadell
ZIP/Postal Code
08208
Country
Spain
Facility Name
Kaohsiung Medical University Chung-Ho Memorial Hospital
City
Kaohsiung
ZIP/Postal Code
80756
Country
Taiwan
Facility Name
Chung Shan Medical University Hospital
City
Taichung
ZIP/Postal Code
40201
Country
Taiwan
Facility Name
China medical university hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
36138330
Citation
Cella D, Lenderking WR, Chongpinitchai P, Bushmakin AG, Dina O, Wang L, Cappelleri JC, Navarro-Compan V. Functional Assessment of Chronic Illness Therapy-Fatigue is a reliable and valid measure in patients with active ankylosing spondylitis. J Patient Rep Outcomes. 2022 Sep 23;6(1):100. doi: 10.1186/s41687-022-00508-0.
Results Reference
derived
PubMed Identifier
28130206
Citation
van der Heijde D, Deodhar A, Wei JC, Drescher E, Fleishaker D, Hendrikx T, Li D, Menon S, Kanik KS. Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2017 Aug;76(8):1340-1347. doi: 10.1136/annrheumdis-2016-210322. Epub 2017 Jan 27.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A3921119&StudyName=Dose-Ranging%20Study%20Of%20Tofacitinib%20In%20Adults%20With%20Active%20Ankylosing%20Spondylitis
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

Dose-Ranging Study Of Tofacitinib In Adults With Active Ankylosing Spondylitis

We'll reach out to this number within 24 hrs