Baricitinib in the Treatment of Refractory Axial Spondyloarthritis Patients: A Comparison With Tofacitinib

NCT06114407 | Unknown Phase 2 DMC

• 1 other identifier: 4548
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 1

Brief Summary

Axial Spondylarthritis (ax-SpA) is an important cause of inflammatory back pain in young adults. Janus kinase inhibitors (JAKi) has been approved for treatment of ax-SpA. Tofacitinib and baricitinib are drugs from same family (JAKi). Baricitinib is relatively less expensive than Tofacitinib. The goal of this non-inferiority clinical trial is to learn about the efficacy of baricitinib in refractory axial spondyloarthritis ( ax-SpA) and to compare its effect with that of tofacitinib. The main questions it aims to answer are:

1. 1.Is baricitinib 4 mg effective in refractory ax-SpA?
2. 2.Is baricitinib non-inferior to tofacitinib in refractory ax-SpA? Participants (treatment group, 92 patients) will be treated with baricitinib 2 mg twice daily for 12 weeks. Ninety two patients getting tofacitinib 10 mg/day (comparison group) will be taken as historical control from another study on the efficacy of tofacitinib in refractory ax-SpA?

Conditions

Spondyloarthritis, Axial

Keywords

Spondyloarthritis; Tofacitinib; Baricitinib; Refractory; Axial

Outcome Measures

Primary Outcomes (1)

• Ankylosing Spondylitis Disease Activity Score-C Reative Protein ( ASDAS-CRP)

  To calculate ASDAS-CRP, besides the value of CRP, the four other items are back pain duration of morning stiffness, peripheral pain/swelling and patient global assessment of disease activity (these are assessed by 0-10cm, visual analogue scale \[VAS\] or 0-10, numerical rating scale \[NRS\]). Four disease activity states were categorized by ASAS: "inactive disease", "moderate disease activity", "high disease activity" and "very high disease activity".The 3 cut-offs chosen to separate these states are: \<1.3 "inactive disease", 1.3 to \<2.1 "low disease activity", 2.1 to \<3.5 "high disease activity" and \>3.5 "very high disease activity". Patients of refractory ax-SpA with high disease activity (ASDAS-CRP≥2.1) will be the entry criteria in this study. Primary outcome will be assessed by ASDAS CRP and a change of ≥ 1.1 units from baseline for clinically important improvement and ≥ 2.0 units for major improvement.

  ASDAS CRP will be assessed at baseline, 4th and 12th week

Secondary Outcomes (6)

• Ankylosing Spondylitis Disease Activity Score-ESR ( ASDAS-ESR)

  ASDAS ESR will be assessed at baseline, 4th and 12th week

• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

  BASDAI will be assessed at baseline, 4th and 12th week

• Bath Ankylosing Spondylitis Functional Index (BASFI)

  BASFI will be assessed at baseline, 4th and 12th week

• Bath Ankylosing Spondylitis Metrology Index (BASMI)

  BASMI will be assessed at baseline, 4th and 12th week

• Maastricht Ankylosing Spondylitis Enthesitis Score (MASES)

  MASES will be assessed at baseline, 4th and 12th week

Other Outcomes (2)

• Health Assessment questionnaire Disability Index (HAQ-DI)

  HAQ-DI will be assessed at baseline, 4th and 12th week

• 36-Item Short Form Survey ( SF-36)

  SF-36 will be assessed at baseline, 4th and 12th week

Study Arms (2)

Baricitinib

EXPERIMENTAL

Participants of 'Baricitinib' arm will be treated with tablet baricitinib 2 mg twice daily for 12 weeks

Drug: Baricitinib 2mg

Tofacitinib

ACTIVE COMPARATOR

Participants of 'Tofacininib' arm getting tablet tofacitinib 5 mg twice daily for 12 weeks will be taken as historical control arm from another study on the efficacy of tofacitinib in refractory axial spondyloarthritis

Drug: Tofacitinib 5 mg

Interventions

Baricitinib 2mg DRUG

Participants of arm 'A' will be treated with tablet baricitinib 2 mg twice daily for 12 weeks

Also known as: Baritinib 2 mg

Baricitinib

Tofacitinib 5 mg DRUG

Participants of arm 'B' getting tablet tofacitinib 5 mg twice daily for 12 weeks will be taken as historical control arm from another study on the efficacy of tofacitinib in refractory axial spondyloarthritis

Also known as: Tofacent 5 mg

Tofacitinib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Patients meeting the ASAS classification criteria for axial spondyloarthritis
• Patients fulfilling the definition of refractory axial spondyloarthritis
• Patients with ASDAS-CRP ≥ 2.1

You may not qualify if:

• Patients who are currently on treatment or had been previously treated with bDMARDs or tsDMARDS (including JAK inhibitors)
• Hemoglobin \< 9 gm/dl
• WBC count \< 4000/cmm, Neutrophil count \< 1000 cmm, Platelet count \< 100000/cmm
• Any current or previous history of serious opportunistic infection including tuberculosis
• Live vaccine within 3 months prior to the first dose
• GFR \< 50 ml/min
• ALT \> 2 times upper limit normal
• Pregnancy, breastfeeding or women of reproductive age group not using effective contraceptive
• Current or previous history of malignancy, lymphoproliferative disease
• New York Heart Association Class III and IV congestive heart failure

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: lead
• Healthcare Pharmaceuticals: collaborator

Study Sites (1)

Bangabandhu Sheikh Mujib Medical University

Dhaka, 1000, Bangladesh

RECRUITING

Related Publications (14)

• Abdal SJ, Yesmin S, Shazzad MN, Azad MAK, Shahin MA, Choudhury MR, Islam MN, Haq SA. Development of a Bangla version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI). Int J Rheum Dis. 2021 Jan;24(1):74-80. doi: 10.1111/1756-185X.14008. Epub 2020 Nov 1.

  PMID: 33135389 BACKGROUND

• Baraliakos X, Kiltz U, Peters S, Appel H, Dybowski F, Igelmann M, Kalthoff L, Krause D, Menne HJ, Saracbasi-Zender E, Schmitz-Bortz E, Vigneswaran M, Braun J. Efficiency of treatment with non-steroidal anti-inflammatory drugs according to current recommendations in patients with radiographic and non-radiographic axial spondyloarthritis. Rheumatology (Oxford). 2017 Jan;56(1):95-102. doi: 10.1093/rheumatology/kew367. Epub 2016 Oct 25.

  PMID: 27997346 BACKGROUND

• Deodhar A, Sliwinska-Stanczyk P, Xu H, Baraliakos X, Gensler LS, Fleishaker D, Wang L, Wu J, Menon S, Wang C, Dina O, Fallon L, Kanik KS, van der Heijde D. Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2021 Aug;80(8):1004-1013. doi: 10.1136/annrheumdis-2020-219601. Epub 2021 Apr 27.

  PMID: 33906853 BACKGROUND

• Leung YY, Lee W, Lui NL, Rouse M, McKenna SP, Thumboo J. Adaptation of Chinese and English versions of the Ankylosing Spondylitis quality of life (ASQoL) scale for use in Singapore. BMC Musculoskelet Disord. 2017 Aug 17;18(1):353. doi: 10.1186/s12891-017-1715-x.

  PMID: 28818056 BACKGROUND

• Machado P, Landewe R, Lie E, Kvien TK, Braun J, Baker D, van der Heijde D; Assessment of SpondyloArthritis international Society. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores. Ann Rheum Dis. 2011 Jan;70(1):47-53. doi: 10.1136/ard.2010.138594. Epub 2010 Nov 10.

  PMID: 21068095 BACKGROUND

• Machado P, Navarro-Compan V, Landewe R, van Gaalen FA, Roux C, van der Heijde D. Calculating the ankylosing spondylitis disease activity score if the conventional c-reactive protein level is below the limit of detection or if high-sensitivity c-reactive protein is used: an analysis in the DESIR cohort. Arthritis Rheumatol. 2015 Feb;67(2):408-13. doi: 10.1002/art.38921.

  PMID: 25332195 BACKGROUND

• Miceli-Richard C, Dougados M. Tracking JAKs in spondyloarthritis: rationale and expectations. Ann Rheum Dis. 2017 Aug;76(8):1325-1326. doi: 10.1136/annrheumdis-2016-210886. Epub 2017 Mar 17. No abstract available.

  PMID: 28314752 BACKGROUND

• Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, Landewe RBM, Van den Bosch FE, Boteva B, Bremander A, Carron P, Ciurea A, van Gaalen FA, Geher P, Gensler L, Hermann J, de Hooge M, Husakova M, Kiltz U, Lopez-Medina C, Machado PM, Marzo-Ortega H, Molto A, Navarro-Compan V, Nissen MJ, Pimentel-Santos FM, Poddubnyy D, Proft F, Rudwaleit M, Telkman M, Zhao SS, Ziade N, van der Heijde D. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2023 Jan;82(1):19-34. doi: 10.1136/ard-2022-223296. Epub 2022 Oct 21.

  PMID: 36270658 BACKGROUND

• Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J, Braun J, Chou CT, Collantes-Estevez E, Dougados M, Huang F, Gu J, Khan MA, Kirazli Y, Maksymowych WP, Mielants H, Sorensen IJ, Ozgocmen S, Roussou E, Valle-Onate R, Weber U, Wei J, Sieper J. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009 Jun;68(6):777-83. doi: 10.1136/ard.2009.108233. Epub 2009 Mar 17.

  PMID: 19297344 BACKGROUND

• Sieper J, Rudwaleit M, Baraliakos X, Brandt J, Braun J, Burgos-Vargas R, Dougados M, Hermann KG, Landewe R, Maksymowych W, van der Heijde D. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009 Jun;68 Suppl 2:ii1-44. doi: 10.1136/ard.2008.104018.

  PMID: 19433414 BACKGROUND

• Smith JA, Colbert RA. Review: The interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheumatol. 2014 Feb;66(2):231-41. doi: 10.1002/art.38291. No abstract available.

  PMID: 24504793 BACKGROUND

• Toussirot E. The Use of Janus Kinase Inhibitors in Axial Spondyloarthritis: Current Insights. Pharmaceuticals (Basel). 2022 Feb 22;15(3):270. doi: 10.3390/ph15030270.

  PMID: 35337068 BACKGROUND

• Veale DJ, McGonagle D, McInnes IB, Krueger JG, Ritchlin CT, Elewaut D, Kanik KS, Hendrikx T, Berstein G, Hodge J, Telliez JB. The rationale for Janus kinase inhibitors for the treatment of spondyloarthritis. Rheumatology (Oxford). 2019 Feb 1;58(2):197-205. doi: 10.1093/rheumatology/key070.

  PMID: 29618084 BACKGROUND

• Zahid-Al-Quadir A, Zaman MM, Ahmed S, Bhuiyan MR, Rahman MM, Patwary I, Das BB, Hossain SA, Paul S, Shahin A, Rahman M, Haq SA. Prevalence of musculoskeletal conditions and related disabilities in Bangladeshi adults: a cross-sectional national survey. BMC Rheumatol. 2020 Dec 16;4(1):69. doi: 10.1186/s41927-020-00169-w.

  PMID: 33323124 BACKGROUND

MeSH Terms

Conditions

Axial Spondyloarthritis; Spondylarthritis

Interventions

baricitinib; tofacitinib

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Study Officials

• Samaresh Das, M B B S

  Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samaresh Das, M B B S

CONTACT

+8801723224832; sam.dmc67@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 28, 2023
• First Posted: November 2, 2023
• Study Start: October 30, 2023
• Primary Completion: June 30, 2024
• Study Completion: December 30, 2024
• Last Updated: December 21, 2023

Record last verified: 2023-12

Locations

BA (1)