Safety and Efficacy of Tofacitinib in the Treatment of NSAID Refractory Axial Spondyloarthritis:A Clinical Trial

NCT03738956 | Unknown Phase 2 DMC

• 1 other identifier: BSMMU/2017/9442
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Title Efficacy and Safety of Tofacitinib in the Treatment of NSAID-Refractory Axial Spondyloarthritis: A Clinical Trial Background: Axial spondyloarthritis (axSpA) is a chronic systemic inflammatory rheumatic disease affecting mainly sacroiliac joints and spine. There are limited options for treatment. Initial treatments are patient's education, regular physical exercise and nonsteroidal antiinflammatory drugs(NSAID). If the patients do not respond to at least two NSAIDs in full dosages for at least one month then it is called NSAID refractory axSpA. In these cases biologics like-tumor necrosis factor α blockers are the options for treatment. Tofacitinib is a new drug has been proven to be effective for treatment of rheumatoid arthritis , psoriasis , inflammatory bowel disease and supposed to be effective in spondyloarthritis. This study is aimed to assess the efficacy and safety of tofacitinib in NSAID refractory ax SpA with a view to find a safe, effective and affordable treatment modality. Method: This open label uncontrolled clinical trial with tofacitinib will be conducted in NSAID refractory axSpA (age \>18 years) patients. Study participants will be enrolled after having informed written consent from the outpatient department of Rheumatology, Bangabandhu sheikh mujib medical university. Assessment of Spondyloarthritis International Society (ASAS) criteria will be followed for diagnosis of ax SpA. Patients failing a trial of 2 different NSAID each for at least 2 weeks with optimum dosage without response or with partial response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 (range, 0-10) or Ankylosing spondylitis disease activity score-C reactive protein(ASDAS-CRP)\>2.1 will be considered as primary entry criteria for this study. Baseline evaluation will include Bath AS Disease Activity Index (BASDAI), Functional Index (BASFI) , Ankylosing spondylitis disease activity score-C reactive protein(ASDASCRP) and Ankylosing spondylitis disease activity score-erythrocyte sedimentation rate(ASDAS-ESR). Laboratory tests like CBC, ESR, CRP, SGPT, Serum creatinine and X-ray pelvis A/P view or X-ray both SI joints modified Ferguson veiw (to see both SI and hip joints ), HLA-B27(if needed), CXR P/A view and MT test or Interferon Gamma Release Assay(IGRA) will be done. After considering inclusion and exclusion criteria eligible patients will be included for this study. All patients will be put on 5mg tofacitinib BD. NSAID and adjuvant analgesics will be used if needed. Follow up will be done at 4th, 12th and 24th week. Response to treatment will be evaluated by assessement of spondyloarthritis society (ASAS) response criteria. More than 20% improvements from baseline will consider as primary response at the end of 12th week. Those patients who will not achieve ASAS20 response at 12th week, will be given 10 mg tofacitinib BD. Efficacy will be assessed at the end of 24th week by ASAS20, ASAS50, ASAS70, ASDAS-ESR, ASDAS-CRP, BASDAI, Bath ankylosing spondylitis functional index(BASFI). Adverse effects will be assesed by history, Physical examinations and investigations. The entire study subjects will be informed about the nature, purpose and implication of the study as well as whole spectrum of benefits and risk of the study. Ethical clearance will be taken from the IRB of BSMMU.

Conditions

Axial Spondyloarthritis

Keywords

Axial spondyloarthritis

Outcome Measures

Primary Outcomes (1)

• Assessment of spondyloarthritis international society 20 response(ASAS 20)

  ASAS 20:It is a composite measurement which means improvement of ≥ 20% in 3 of the following 4 domains without 20% worsening in the remaining domain Four domains 1. Bath ankylosing spondylitis functional index(BASFI)-The 10 items index of daily functional activities completed on a numerical rating scale (NRS) 0-10. The higher the BASFI score, the more severe the limitation of function due to AxSpA 2. Morning stiffness 3. Patient global assessment 4. Pain

  At the end of 3rd month

Secondary Outcomes (2)

• Ankylosing Spondylitis Disease Activity Score- C reactive protein(ASDASCRP)

  At the end of 6 month

• Ankylosing Spondylitis Disease Activity Score-Erythrocyte sedimentation rate(ASDASESR)

  At the end of 6th month

Study Arms (1)

Open label clinical trial

EXPERIMENTAL

NSAID refractory axial spondyloarthritis patients who are eligible after considering inclusion and exclusion crietria will be put on 5 mg tofacitinib BD ,at the end of 1st and 3rd month they will be assessed for safety and efficacy.Those who will not respond will be put on 10 mg tofacitinib BD.All patients will be assessed at the end of 6th month.If any adverse event occur they will be treated accordingly.

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

The study subjects fulfilling the inclusion criteria will receive tofacitinib 5mg BD. All the patients in the study group will go through disease history, clinical examination and baseline investigations. Baseline charachteristics and variables will be recorded at initiation of therapy, 4th, 12th and 24th week. Primary endpoint of efficacy will be assessed using ASAS 20 response at the end of 12 th wk. At the end of 12 th week, those patients will achieve primary endpoint will continue with the same dose and those patients who will not achieve primary endpoint will be put on tofacitinib10 mg BD. Those patients who will not respond to treatment at the end of 24 th wk will discontinue the therapy and put on alternative treatment.

Open label clinical trial

Eligibility Criteria

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

You may qualify if:

• The subjects will be considered if they fulfill the following criteria
• Subjects greater than 18 years of age
• Patients fulfilling the ASAS classification criteria for axial SpA including both non radiographic axial spondyloarthritis (nr-Ax SpA) and ankylosing spondylitis(AS)
• Patients with axSpA underwent a trial of at least 2 course of NSAIDs with optimum doses for at least 1 month without response or with partial response
• Patients with BASDAI ≥4 or ASDAS-CRP\>2.1

You may not qualify if:

• The subjects will be excluded if they have any of the
• Systemic infections requiring hospital admission during the last 6 months
• Active infections and/or a history of chronic or recurrent serious infective diseases, opportunistic infections
• Hemoglobin (Hb) \< 9 g/dl
• White blood cell count \< 4000, Neutrophil count \< 1000, Platelet count \< 100000/mm3
• Live vaccines within 3 months prior to the first dose
• Serum creatinine \> upper limit of normal reference range
• GFR less than 50 mL/min
• Alanine aminotransaminase (ALT) more than 2 times of ULN
• Pregnant or breast feeding females of child-bearing potential not using highly effective contraception
• Evidence or history of malignancy, with the exception of adequately treated or excised non-metastatic basal or squamous cell cancer of the skin or cervical carcinoma in situ
• New York Heart Association Class III and IV congestive heart failure
• Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease

Sponsors & Collaborators

• Globe Pharmaceuticals Limited: lead
• Globe pharmaceuticals Ltd, Dhaka, Bangladesh: collaborator

Study Sites (1)

Bangabandhu sheikh mujib medical university

Dhaka, 1205, Bangladesh

RECRUITING

Related Publications (5)

• Boonen A, van der Heijde D, Landewe R, Guillemin F, Rutten-van Molken M, Dougados M, Mielants H, de Vlam K, van der Tempel H, Boesen S, Spoorenberg A, Schouten H, van der Linden S. Direct costs of ankylosing spondylitis and its determinants: an analysis among three European countries. Ann Rheum Dis. 2003 Aug;62(8):732-40. doi: 10.1136/ard.62.8.732.

  PMID: 12860728 BACKGROUND

• Anderson JJ, Baron G, van der Heijde D, Felson DT, Dougados M. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Arthritis Rheum. 2001 Aug;44(8):1876-86. doi: 10.1002/1529-0131(200108)44:83.0.CO;2-F.

  PMID: 11508441 BACKGROUND

• Sykes WS, Lawrence RC. Helium in Anaesthesia. Br Med J. 1938 Aug 27;2(4051):448-9. doi: 10.1136/bmj.2.4051.448. No abstract available.

  PMID: 20781696 BACKGROUND

• Braun J, Pham T, Sieper J, Davis J, van der Linden S, Dougados M, van der Heijde D; ASAS Working Group. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis. 2003 Sep;62(9):817-24. doi: 10.1136/ard.62.9.817.

  PMID: 12922952 BACKGROUND

• Braun J, Inman R. Clinical significance of inflammatory back pain for diagnosis and screening of patients with axial spondyloarthritis. Ann Rheum Dis. 2010 Jul;69(7):1264-8. doi: 10.1136/ard.2010.130559.

  PMID: 20566619 BACKGROUND

MeSH Terms

Conditions

Axial Spondyloarthritis

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Asadul Islam, MBBS

  Globe Pharmaceuticals Limited

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Asadul Islam, MBBS

CONTACT

+88-01721446630; asad.kmc13@gmail.com

Prayush Sharma, MBBS

CONTACT

+8801535157897; drprayush@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident

Model Details: Eligible patients will be given tofacitinib 5 mg BD ,at the end of 1st and 3rd months they will be assessed for safety and efficacy.At 3rd months if any patient wll not responds then they will be given tofacitinib 10 mg BD,at the end of 6th month they will be assessed for safety and efficacy.If any adverse events occur they will be treated accordingly.

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 13, 2018
• Study Start: September 1, 2017
• Primary Completion: December 30, 2018
• Study Completion: December 31, 2018
• Last Updated: November 13, 2018

Record last verified: 2018-11

Locations

BA (1)