| CTRI Number |
CTRI/2024/07/071400 [Registered on: 26/07/2024] Trial Registered Prospectively |
| Last Modified On: |
16/07/2024 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Biological |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Use of Tofacitinib and Adalimumab in Spondyloarthritis |
|
Scientific Title of Study
|
Comparing Efficacy of Tofacitinib v/s Adalimumab In Axial Spondyloarthritis Randomised, Open Label, Non Inferiority Trial |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Maddineni Abhi chandra |
| Designation |
Senior Resident, Department of Clinical Immunology and Rheumatology |
| Affiliation |
IMS and SUM Hospital |
| Address |
Room no-67, Department of Clinical Immunology and Rheumatology,IMS and SUM hospital, K-8, Kalinga Nagar, Po.-Ghatikia, Bhubaneswar,
Khordha
ORISSA
751003
India |
| Phone |
06281335841 |
| Fax |
|
| Email |
abhichandra.mac@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Pradeepta Sekhar Patro |
| Designation |
Head of Department, Department of Clinical Immunology and Rheumatology |
| Affiliation |
IMS and SUM Hospital |
| Address |
Room no-68, Department of Clinical Immunology and Rheumatology,IMS and SUM hospital, K-8, Kalinga Nagar, Po.-Ghatikia, Bhubaneswar,
Khordha
ORISSA
751004
India |
| Phone |
09721799997 |
| Fax |
|
| Email |
drpradeepta07@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Pradeepta Sekhar Patro |
| Designation |
Head of Department, Department of Clinical Immunology and Rheumatology |
| Affiliation |
IMS and SUM Hospital |
| Address |
Room no-68, Department of Clinical Immunology and Rheumatology,IMS and SUM hospital, K-8, Kalinga Nagar, Po.-Ghatikia, Bhubaneswar,
Khordha
ORISSA
751004
India |
| Phone |
09721799997 |
| Fax |
|
| Email |
drpradeepta07@gmail.com |
|
|
Source of Monetary or Material Support
|
| Indian Rheumatology Association, Secretariat & Mailing Address- Prof. (Dr.) Aman Sharma Room No 2024/2025, Second Floor, New OPD Block , PGIMER, Chandigarh. 0172 2756681.
Email - secretary@indianrheumatology.org, amansharma74@yahoo.com Mob: 981429779 |
| Institute of Medical Sciences and Siksha O Anusandhan University,K-8, Kalinga Nagar, Po. - Ghatikia, Bhubaneswar, 751003, Orissa |
|
|
Primary Sponsor
|
| Name |
Indian Rheumatology Association |
| Address |
Room no 2024/2025, Second floor, New opd block,PGIMER, Chandigarh, 0172 2756681 |
| Type of Sponsor |
Other [The Professional Organization of Clinical Immunologists and Rheumatologists in India] |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Maddineni Abhi Chandra |
Institute of Medical Sciences and Siksha O Anusandhan University |
Room No 68, Department of Clinical Immunology and Rheumatology, Institute of Medical Sciences and SOA University, K-8, Kalinga Nagar, Po. - Ghatikia, Bhubaneswar, 751003, Orissa
Khordha
ORISSA |
6281335841
abhichandra.mac@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee IMS and SUM Hospital |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: M450||Ankylosing spondylitis of multiplesites in spine, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Adalimumab |
Injection adalimumab 40mg is given subcutaneously for every 2 weeks for total of 12 weeks |
| Intervention |
Tofacitinib |
Tablet tofacitinib 5mg twice daily is given for 12 weeks |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
60.00 Year(s) |
| Gender |
Both |
| Details |
Aged between 18 to 60 years fulfilling the Modified New York Criteria for Ankylosing Spondylitis (1984) & ASAS criteria for Axial Spondyloarthritis
High Disease Activity defined by ASDAS ≥ 2.1.
Intolerance or inadequate response to at least two different oral NSAIDS, given maximum dose for a total duration of at least 4 weeks.
All patients must give written informed consent prior to enrolment
|
|
| ExclusionCriteria |
| Details |
Patient with previous history of biological usage
Past or present history of Inflammatory Bowel Disease
Past or present history of Psoriasis
Blood dyscrasias - anemia, leucopenia, thrombocytopenia
Renal insufficiency
Liver Insufficiency- Bilirubin & liver enzymes more than 1.5 times the upper limit of normal (ULN) at screening
Complete ankylosis of the spine.
Patients having active tuberculosis or positive for latent tuberculosis
Latent Hepatitis B Positive status [ Anti HBc Ig positive]
History of recurrent herpes zoster or herpes simplex.
Present malignancy or with a history of malignancy
Current or past history thromboembolism or presence of risk factors for the same.
History of Coronary artery disease or presence of risk factors for cardiovascular disease
Pregnant female or breast-feeding mothers
H/O or current demyelinating Disease
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To compare ASAS 20 response rate among Tofacitinib and Adalimumab group in patients with Axial Spondyloarthritis |
Week 12 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
 To compare ASAS 40 response rate among Tofacitinib & Adalimumab patients group.
 Mean Change in disease activity assessed by BASDAI; BASMI; ASDAS – CRP; BASFI; MASES; SJC 44; ESR ; CRP; SPARCC Score – SI Joint
 Mean Change in serum DKK-1, IL-17 levels
 Adverse events
|
12 weeks |
|
|
Target Sample Size
|
Total Sample Size="202"
Sample Size from India="202"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
|
Date of First Enrollment (India)
|
28/07/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="3"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Background: Axial spondyloarthritis (axSpA), is a persistent inflammatory condition affecting the axial skeleton. Cytokines like TNF, IL-17, IL-23 are implicated in pathogenesis of AxSpA, but studies assessing their role as biomarkers of disease have conflicting results. Dickkopf-1 (DKK-1) is an inhibitor of Wnt signalling, which is a crucial pathway affecting bone formation and its deregulation plays a role in Spondyloarthritis. There is conflicting data on levels of DKK-1 in Spondyloarthritis and correlation of its level with treatment with TNF inhibitors & radiographic progression in Axial Spondyloarthritis. ASAS-EULAR recommends Non Steroidal Anti Inflammatory Agents [ NSAIDs] as first line for treatment of AS & options for failure of NSAIDs include Tumor Necrosis Factor Inhibitors [ TNFi], IL-17 Inhibitors, JAK-Inhibitors, but there are no head to head trials comparing efficacy of these agents. Objectives: ASAS 20 response at week 12 in the study population receiving Adalimumab & Tofacitinib. Methods: In this 12-week open-label, prospective, parallel arm study; 184 patients fulfilling Modified New York Criteria , ASAS criteria for Axial Spondyloarthritis, will be randomly assigned in a 1:1 ratio to receive Adalimumab or Tofacitinib, in combination with background therapy. The ASAS 20 response, other disease activity indices, change in SPARCC Score of SI Joint form baseline and adverse event profile will be compared. The correlation of IL-17, DKK-1 levels with treatment response & radiographic progression will be analysed. Novelty: First study comparing Adalimumab & Tofacitinib correlating the serum IL-17, DKK-1 levels with treatment response & radiographic progression in Axial Spondyloarthritis. Expected Outcomes: Tofacitinib is non inferior to Adalimumab in treatment of Axial Spondyloarthritis patients with no response to NSAIDs |