Risk of Tuberculous and Other Infections in Patients of Spondyloarthritis Treated With Tofacitinib in Bangladesh

NCT03504072 | Unknown Phase 4 DMC

• 1 other identifier: 2018/547
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

Treatment failure of Spondyloarthropathies (SpA) leads to marked functional disability, higher rates of morbidity, mortality and poor quality of life. In TB endemic countries effective and safe drugs are to be in hand to manage this group of patients. The aim of this study will be to evaluation the risk of tuberculosis and other infections in refractory SpA patients treated with tofacitinib. After having consent 174 adults will be enrolled. Follow up period will be 9 months (visits 0, 1, 3, 6 and 9). Study subjects (87) will receive tofacitinib (5 mg 12 hourly). Control patients will get etanercept (50 mg subcutaneously every 7 days interval for 1st month then 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval till final visit. Treatment efficacy assessment tool will be BASDAI, ASDAS-ESR, ASDAS-CRP and ASQoL for quality of life. Occurrences of tuberculosis and serious infection will be the primary end point of this study. The quantitative variables like ESR, CRP, BASDAI, ASDAS-ESR, ASDAS-CRP and ASQoL scores will be computed as mean and SD. Occurrences of TB and infection will be expressed in number and percentage. In between groups according to data distribution, students't test or ManWhitny U test will be done. The P value \<0.05 will be considered significant. Each patient will enjoy every right to participate or refuse or even withdraw from the study at any point of time. Anonymity and data confidentiality will be maintained strictly. Ethical clearance will be obtained from Institutional Review Board (IRB) of BSMMU. The expected utility of this study will be; a) reporting on occurrence of TB and other infections in SpA patients with tofacitinib and etanercept, b) if identified safe and effective physician can use the agents without fear, c) for dose spacing of etanercept the cumulative dose will be low might make the drug affordable and also reduce the risk of TB and other infections, d) for spaced follow up schedule there will be minimized physician visit, lab testing etc.

Conditions

Spondyloarthritis

Keywords

Etanercept; Infection; Tofacitinib; Tuberculosis; Spondyloarthritis

Outcome Measures

Primary Outcomes (1)

• Occurrence of Tuberculosis

  While on trial drug occurrence of tuberculosis either pulmonary or extra pulmonary

  9th months

Secondary Outcomes (1)

• improvement of disease activity measures of spondyloarthritis by >40%

  at 9th month

Study Arms (2)

Tofacitinib 5mg

ACTIVE COMPARATOR

tofacitinib 5 mg 12 hourly daily for 9 months. Evaluation schedule will be baseline, 1st month, 3rd months and 3 monthly for 9 months. relevant investigations will be done at each visit. occurrence of tuberculosis and infections will be recorded at follow up visits.

Drug: Tofacitinib 5 mg,

Etanercept 50 mg

ACTIVE COMPARATOR

Etanercept 50 mg subcutaneously every 7 days interval for 1st month then, Etanercept 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval for 9 months. Occurrence of tuberculosis and infections will be recorded at follow up visits.

Drug: Etanercept

Interventions

Tofacitinib 5 mg, DRUG

tofacitinib 5 mg 12 hourly daily for 9 months

Also known as: tofacitinib

Tofacitinib 5mg

Etanercept DRUG

Etanercept 50 mg sc every 7 days interval in 1st month, every 15 days interval in 2nd month and then every 21 days interval from 3rd month onward upto 9 months

Also known as: Etanercept 50 mg

Etanercept 50 mg

Eligibility Criteria

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

You may qualify if:

• IBP criteria (4 out of 5 parameters present more than 3 months) Inflammatory back pain 1) Age of onset \<45 yr 2) Insidious onset 3) Improvement with exercise 4) No improvement with rest 5) Pain at night (with improvement upon arising)
• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of \> 4 (range, 0-10)
• Failing to response to 2 NSAIDs in full therapeutic dose or withdrawal for intolerance in four consecutive weeks
• Age \> 18 years
• Agreed to participate in the study

You may not qualify if:

• Known case of allergic patients
• Pregnancy
• Patient with any active or history of any chronic or recurrent or serious or opportunistic infection/sepsis
• Known case of chronic kidney disease (Cl cr \<40 mL/minute)
• Moderate to severe liver disease of any type
• Lymphopenia (Lymphocyte \<500 cells/mm3 of blood)
• Neutropenia (Neutrophil \<1000 cells/mm3 of blood)
• Anaemia (Hb \< 9 g/dl)
• Who have been exposed to tuberculosis
• Chest X-ray suggestive of pulmonary tuberculosis
• Patients who do not want to participate in this study

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: lead

Study Sites (1)

Bangabandhu Sheikh Mujib Medical University

Dhaka, Bangladesh

RECRUITING

MeSH Terms

Conditions

Spondylarthritis; Infections; Tuberculosis

Interventions

tofacitinib; Etanercept

Condition Hierarchy (Ancestors)

Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Study Officials

• Shaikh A Al Mamun, MBBS

  Member secretary

  STUDY CHAIR

Central Study Contacts

Nazrul N Islam, FCPS, MD

CONTACT

8801678112396; islam1nazrul@gmail.com, islam1nazrul@bsmmu.edu.bd

Nira Ferdous, FCPS

CONTACT

8801816455317; nira1ferdous@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Follow up period will be 9 months (visits 0, 1, 3, 6 and 9). Study subjects (87) will receive toficitinib (5 mg 12 hourly). Control patients will get eternacept (50 mg subcutaneously every 7 days interval for 1st month then 50 mg in 15 days interval for 2nd month then 50 mg every 21 days interval till final visit.

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: April 20, 2018
• Study Start: January 16, 2018
• Primary Completion: June 30, 2019
• Study Completion: December 31, 2019
• Last Updated: April 23, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)