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

NCT01786668 | Completed Phase 2 Results

• 2 other identifiers: A39211192011-005689-39
• Study Type: interventional
• Target: 208
• Locations: 10 countries
• Sites: 67

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.

Conditions

Ankylosing Spondylitis

Keywords

Ankylosing Spondylitis; Spondylitis; Ankylosing; Spondyloarthritis; Spondyloarthropathy; Oral preparation

Outcome Measures

Primary Outcomes (2)

• 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.

  Week 12

• 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.

  Baseline, Week 12

Secondary Outcomes (21)

• Percentage of Participants Achieving 20% Improvement in ASAS Score at Weeks 2, 4 and 8

  Baseline, Week 2, Week 4, Week 8

• 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

  Baseline, Week 12

• Change From Baseline in SPARCC MRI Index of Disease Activity Score of the Spine at Week 12

  Baseline, Week 12

• Change From Baseline in Modified Berlin Ankylosing Spondylitis Spine Magnetic Resonance Imaging Activity Score (ASspiMRI) of the Spine at Week 12

  Baseline, Week 12

• Percentage of Participants Achieving 40% Improvement in ASAS Score at Weeks 2, 4, 8 and 12

  Baseline, Week 2, Week 4, Week 8, Week 12

Study Arms (4)

Tofacitinib 2 mg

EXPERIMENTAL

Drug: Tofacitinib 2 mg

Tofacitinib 5 mg

EXPERIMENTAL

Drug: Tofacitinib 5 mg

Tofacitinib 10 mg

EXPERIMENTAL

Drug: Tofacitinib 10 mg

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tofacitinib 2 mg DRUG

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

Tofacitinib 2 mg

Tofacitinib 5 mg DRUG

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

Tofacitinib 5 mg

Tofacitinib 10 mg DRUG

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

Tofacitinib 10 mg

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (67)

Desert Medical Imaging

Indian Wells, California, 92210, United States

Location

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

Arthritis & Rheumatology Associates

Clearwater, Florida, 33756, United States

Location

Millennium Research

Ormond Beach, Florida, 32174, United States

Location

Southwest Florida Clinical Research Center

Tampa, Florida, 33609, United States

Location

Covance Central Laboratory Services,Inc

Indianapolis, Indiana, 46214, United States

Location

Klein & Associates, M.D., P.A.

Hagerstown, Maryland, 21740, United States

Location

Progressive Radiology

Hagerstown, Maryland, 21740, United States

Location

Advanced Medical Imaging (MRI center)

Lincoln, Nebraska, 68506, United States

Location

Arthritis Center of Nebraska (X-ray center)

Lincoln, Nebraska, 68516, United States

Location

Physician Research Collaboration, LLC

Lincoln, Nebraska, 68516, United States

Location

Charlotte Radiology/ Carolina Imaging Services

Ballantyne, North Carolina, 28277, United States

Location

Joint and Muscle Research Institute

Charlotte, North Carolina, 28204, United States

Location

Presbyterian Imaging

Charlotte, North Carolina, 28207, United States

Location

Paramount Medical Research & Consulting, LLC

Middleburg Heights, Ohio, 44130, United States

Location

Premier Physicians Centers

Westlake, Ohio, 44145, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Clinical Research Center of Reading, LLC

Wyomissing, Pennsylvania, 19610, United States

Location

Investigational Drug Service

Seatle, Washington, 98122, United States

Location

Seattle Rheumatology Associates

Seattle, Washington, 98122, United States

Location

Arthritis Northwest, PLLC

Spokane, Washington, 99204, United States

Location

Institut de Rhumatologie de Montreal

Montreal, Quebec, H2L 1S6, Canada

Location

G.R.M.O. Inc

Québec, Quebec, G1V 3M7, Canada

Location

Artroscan s.r.o.

Ostrava, Czech Republic, 722 00, Czechia

Location

Revmatologicky ustav

Prague, 128 50, Czechia

Location

Revmatologicka ambulance

Prague, 140 00, Czechia

Location

Mediscan Group s.r.o.

Praha 11- Chodov, 14800, Czechia

Location

Medical Plus

Uherské Hradiště, 68601, Czechia

Location

Charité Universitaetsmedizin Berlin

Berlin, 12203, Germany

Location

Praxis fuer klinische Studien

Hamburg, 22415, Germany

Location

Gemeinschaftspraxis Dres. von Hinueber / Demary

Hildesheim, 31134, Germany

Location

Immunologisches Zentrum Vogelsang-Gommern GmbH

Vogelsang-Gommern, 39245, Germany

Location

Dr. Rethy Pál Korhaz es Rendelointezet, Reumatologia

Békéscsaba, 5600, Hungary

Location

Orszagos Reumatologiai es Fiziotherapias Intezet II. Reumatologiai Osztaly

Budapest, 1023, Hungary

Location

Qualiclinic Kft

Budapest, 1036, Hungary

Location

Synexus Magyarorszag Kft. - Synexus Hungary Clinical Research Centre

Budapest, 1036, Hungary

Location

Debreceni Egyetem Orvos- és Egészségtudományi Centrum

Debrecen, 4032, Hungary

Location

CRU Hungary Kft.

Szikszó, 3800, Hungary

Location

Csolnoky Ferenc Korhaz Reumatologiai Osztaly

Veszprém, H-8200, Hungary

Location

NZOZ Lecznica MAK-MED s.c.

Nadarzyn, Masovian Voivodeship, 05-830, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej Centrum Osteoporozy i Chorob Kostno-Stawowych

Bialystok, 15- 879, Poland

Location

Szpital Uniwersytecki nr 2 im. dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

Centrum Kliniczno-Badawcze J. Brzezicki, B. Gornikiewicz-Brzezicka Lekarze Spolka Partnerska

Elblag, 82-300, Poland

Location

Medica Pro Familia Sp. z o.o. S.K.A. Oddzial Katowice

Katowice, 40-954, Poland

Location

Malopolskie Centrum Medyczne S.C.

Krakow, 30-510, Poland

Location

Zespol Poradni Specjalistycznych Reumed Filia Onyksowa

Lublin, 20-582, Poland

Location

Twoja Przychodnia - Centrum Medyczne Nowa Sol

Nowa Sól, 67-100, Poland

Location

NZOZ Nasz Lekarz Praktyka Grupowa Lekarzy Rodzinnych z Przychodnia Specjalistyczna w Toruniu

Torun, 87-100, Poland

Location

Federal State Budgetary Institution

Moscow, 115522, Russia

Location

OOO AVA-PETER "Scandinavia clinic"

Saint Petersburg, 191014, Russia

Location

Saint-Petersburg State Budgetary Healthcare Institution

Sestroretsk, 197706, Russia

Location

SBEI HPE Ural State Medical University of MoH of RF based on Municipal Budgetary Institution

Yekaterinburg, 620149, Russia

Location

Chonnam National University Hospital

Gwangju, 501-757, South Korea

Location

INHA University Hospital

Incheon, 400-711, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Ajou University Hospital

Suwon, 443-721, South Korea

Location

Complexo Hospitalario Universitario A Coruna

A Coruña, A Coruna, 15006, Spain

Location

Hospital Clinico Universitario Santiago de Compostela

Santiago de Compostela, A Coruna, 15706, Spain

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Cordoba, 14004, Spain

Location

Hospital Universitario De La Paz

Madrid, 28046, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, 08208, Spain

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

Location

China medical university hospital

Taichung, 40447, Taiwan

Location

Related Publications (8)

• Deodhar A, Akar S, Curtis JR, El-Zorkany B, Magrey M, Wang C, Wu J, Makgoeng SB, Vranic I, Menon S, Fleishaker DL, Diehl AM, Fallon L, Yndestad A, Landewe RBM. Integrated safety analysis of tofacitinib from Phase 2 and 3 trials of patients with ankylosing spondylitis. Adv Rheumatol. 2024 Dec 18;64(1):87. doi: 10.1186/s42358-024-00402-x.

  PMID: 39695887 DERIVED

• Norton H, Sliwinska-Stanczyk P, Hala T, El-Zorkany B, Stockert L, Mundayat R, Wang L, Ritchlin CT. Tofacitinib Efficacy/Safety in Patients with Ankylosing Spondylitis by Baseline Body Mass Index: A Post Hoc Analysis of Phase 2/3 Trials. Rheumatol Ther. 2025 Feb;12(1):67-84. doi: 10.1007/s40744-024-00726-6. Epub 2024 Dec 5.

  PMID: 39636343 DERIVED

• Deodhar A, Baraliakos X, Magrey M, Gensler LS, Thorat AV, Pemmaraju SK, Cadatal MJ, Nash P. Efficacy and Safety of Tofacitinib in Ankylosing Spondylitis by Baseline C-Reactive Protein Level: Post Hoc Analysis of Phase II and Phase III Clinical Trials. J Rheumatol. 2024 Aug 1;51(8):772-780. doi: 10.3899/jrheum.2023-1198.

  PMID: 38825359 DERIVED

• Kristensen LE, Deodhar A, Leung YY, Vranic I, Mortezavi M, Fallon L, Yndestad A, Kinch CD, Gladman DD. Risk Stratification of Patients with Psoriatic Arthritis and Ankylosing Spondylitis for Treatment with Tofacitinib: A Review of Current Clinical Data. Rheumatol Ther. 2024 Jun;11(3):487-499. doi: 10.1007/s40744-024-00662-5. Epub 2024 May 2.

  PMID: 38696034 DERIVED

• Magrey M, Wei JC, Yndestad A, Bushmakin AG, Cappelleri JC, Dina O, Deodhar A. Relationships of Work Productivity and Activity Impairment With Patient-Reported Outcomes in Ankylosing Spondylitis: Results From Two Trials. Arthritis Care Res (Hoboken). 2024 Mar;76(3):359-365. doi: 10.1002/acr.25267. Epub 2024 Jan 5.

  PMID: 37909386 DERIVED

• Ostergaard M, Wu J, Fallon L, Sherlock SP, Wang C, Fleishaker D, Kanik KS, Maksymowych WP. Tofacitinib Reduces Spinal Inflammation in Vertebral Bodies and Posterolateral Elements in Ankylosing Spondylitis: Results from a Phase 2 Trial. Rheumatol Ther. 2023 Aug;10(4):1001-1020. doi: 10.1007/s40744-023-00564-y. Epub 2023 Jun 18.

  PMID: 37331992 DERIVED

• 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.

  PMID: 36138330 DERIVED

• 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.

  PMID: 28130206 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Spondylitis, Ankylosing; Spondylitis; Spondylarthritis; Spondylarthropathies

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis; Bone Diseases, Infectious; Infections

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2013
• First Posted: February 8, 2013
• Study Start: April 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: June 10, 2016
• Results First Posted: June 10, 2016

Record last verified: 2016-05

Locations

ES (7); TW (3); CA (2); CZ (5); DE (4); US (22); HU (7); PL (9); RU (4); KR (4)