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

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ClinicalTrials.gov Identifier: NCT03738956
Recruitment Status : Recruiting
First Posted : November 12, 2018
Last Update Posted : November 12, 2018
Sponsor:
Collaborator:
Globe pharmaceuticals Ltd, Dhaka, Bangladesh
Information provided by (Responsible Party):
Dr.Md.Asadul Islam, Globe Pharmaceuticals Limited

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.


Condition or disease Intervention/treatment Phase
Axial Spondyloarthritis Drug: Tofacitinib Phase 2 Phase 3

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Tofacitinib in the Treatment of NSAID Refractory Axial Spondyloarthritis:A Clinical Trial
Actual Study Start Date : September 1, 2017
Estimated Primary Completion Date : December 30, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Open label clinical trial
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

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.





Primary Outcome Measures :
  1. Assessment of spondyloarthritis international society 20 response(ASAS 20) [ Time Frame: At the end of 3rd month ]

    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


Secondary Outcome Measures :
  1. Ankylosing Spondylitis Disease Activity Score- C reactive protein(ASDASCRP) [ Time Frame: At the end of 6 month ]
    ASDAS-CRP: 0.121×total back pain+0.110×patient global+0.073×peripheral pain/swelling+0.058×duration of morning stiffness+0.579×Ln(CRP+1).

  2. Ankylosing Spondylitis Disease Activity Score-Erythrocyte sedimentation rate(ASDASESR) [ Time Frame: At the end of 6th month ]
    ASDAS-ESR: 0.113×patient global+0.293xESR−−−−√+0.086×peripheral pain/swelling+0.069×duration of morning stiffness+0.079×total back pain.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subjects will be considered if they fulfill the following criteria

    1. Subjects greater than 18 years of age
    2. Patients fulfilling the ASAS classification criteria for axial SpA including both non radiographic axial spondyloarthritis (nr-Ax SpA) and ankylosing spondylitis(AS)
    3. 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
    4. Patients with BASDAI ≥4 or ASDAS-CRP>2.1

Exclusion Criteria:

  • The subjects will be excluded if they have any of the

    1. Systemic infections requiring hospital admission during the last 6 months
    2. Active infections and/or a history of chronic or recurrent serious infective diseases, opportunistic infections
    3. Hemoglobin (Hb) < 9 g/dl
    4. White blood cell count < 4000, Neutrophil count < 1000, Platelet count < 100000/mm3
    5. Live vaccines within 3 months prior to the first dose
    6. Serum creatinine > upper limit of normal reference range
    7. GFR less than 50 mL/min
    8. Alanine aminotransaminase (ALT) more than 2 times of ULN
    9. Pregnant or breast feeding females of child-bearing potential not using highly effective contraception
    10. 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
    11. New York Heart Association Class III and IV congestive heart failure
    12. Any lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03738956


Contacts
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Contact: Asadul Islam, MBBS +88-01721446630 asad.kmc13@gmail.com
Contact: Prayush Sharma, MBBS +8801535157897 drprayush@gmail.com

Locations
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Bangladesh
Bangabandhu sheikh mujib medical university Recruiting
Dhaka, Bangladesh, 1205
Contact: Asadul Islam, MBBS    +8801721446630    asad.kmc13@gmail.com   
Contact: Prayush Sharma, MBBS    +8801535157897    drprayush@gmail.com   
Principal Investigator: Asadul Islam, MBBS         
Sponsors and Collaborators
Globe Pharmaceuticals Limited
Globe pharmaceuticals Ltd, Dhaka, Bangladesh
Investigators
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Principal Investigator: Asadul Islam, MBBS Globe Pharmaceuticals Limited

Publications:
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Responsible Party: Dr.Md.Asadul Islam, Resident, Globe Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT03738956     History of Changes
Other Study ID Numbers: BSMMU/2017/9442
First Posted: November 12, 2018    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Dr.Md.Asadul Islam, Globe Pharmaceuticals Limited:
Axial spondyloarthritis
Additional relevant MeSH terms:
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Protein Kinase Inhibitors
Enzyme Inhibitors
Spondylarthritis
Spondylitis
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Arthritis
Joint Diseases
Tofacitinib
Molecular Mechanisms of Pharmacological Action