Back to resultsTofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease. (RAILDTo)
Primary Purpose
Rheumatoid Arthritis, Interstitial Lung Disease
Status
Recruiting
Phase
Phase 2
Locations
Mexico
Study Type
Interventional
Intervention
Tofacitinib
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis, Interstitial Lung Disease, Usual interstitial pneumonia, Tofacitinib, Rheumatoid Arthritis-related interstitial lung disease
Eligibility Criteria
Inclusion Criteria:
- Patients must fulfill ACR/EULAR 2010 RA classification criteria.
- Patients must have an interstitial lung disease confirmed by a high-resolution computed tomography scan or a surgical lung biopsy. Nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphocytic pneumonia, and organized pneumonia, either by HRCT or surgical biopsy, will be included.
- Patients must be 18 years of age or older.
- There is no evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB).
- Patients must discontinue using the non-permitted medications: leflunomide, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, and any biologic disease-modifying drug (bDMDARDs) such as anti-TNF therapy, rituximab, tocilizumab, etc. Patients must have a stable prednisone dose of ≤ 10 mg/ PO/day for at least three months.
- All patients must have stable doses of prednisone during the last three months of follow-up, and the prednisone dose must be ≤ 10 mg/day. Patients without a prednisone history in the previous three months may also be included in the protocol.
Exclusion Criteria:
- Seropositivity for the following infections: HIV, HBV, and HCV.
- Absolute neutrophil count ≤ 1,200/L
- Absolute platelet count ≤ 100,000 /L
- Severe renal damage with GFR < 30 ml/min based on CKD-EPI formula.
- AST or ALT greater than 1.5 times the upper limit of normal AST and ALT levels
- Severe hepatic, hematologic, gastrointestinal, cardiac, and neurological disease may put the patient´s life at risk regardless of ILD severity.
- Severe active infections at baseline evaluation, such as pneumonia, urinary tract infections, meningitis.
8 History of drug abuse or alcoholism. 9. History of any malignancy 10. Patients with an FVC < 40% of what is expected will be excluded from the study.
-
Sites / Locations
- Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío VillegasRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Tofacitinib Arm
Arm Description
Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months.
Outcomes
Primary Outcome Measures
Incidence and severity of adverse events
Adverse event: Any untoward medical occurrence in a subject being included in the trial, in which the event may not necessarily have a causal relationship with the treatment. Examples of adverse events are as follows: abnormal test findings, clinically significant symptoms and signs, hypersensitivity reactions, and progression or worsening of RA or RA-ILD.
Secondary Outcome Measures
Forced Vital Capacity (liters)
Forced vital capacity (FVC) on spirometry, the data will be presented as percentages of predicted values, according to sex, age, height, and weight.
Carbon monoxide diffusing capacity (DLCO) (mil/min/mmHg)
The data will be presented as percentages of predicted values, according to sex, age, height, and weight.
6 minutes walk test
walked metters in 6 minutes
Rheumatoid arthritis disease activity according to the simplified disease activity (SDAI) index.
The SDAI index consists of the algebraic sum of the following items: tender joint count, swollen joint count, c-reactive protein, rheumatoid arthritis activity according to the patient, disease activity according to the attending physician.
Rheumatoid arthritis disease activity according to the Disease Activity Score Index (DAS28)
The DAS28 score is calculated with the tender joint count, swollen joint count, eritrosedimentation rate, patients' global health assesment aacording with the following formula DAS28 = ( 0.56 * sqr(TJC)) + (0.28 * sqr(SJC)) + ( 0.7 * ln(VSG)) + (0.014 * GH)
Full Information
NCT ID
NCT05246293
First Posted
January 17, 2022
Last Updated
April 26, 2023
Sponsor
National Institute of Respiratory Diseases, Mexico
1. Study Identification
Unique Protocol Identification Number
NCT05246293
Brief Title
Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease.
Acronym
RAILDTo
Official Title
Safety and Tolerability of Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease (RAILDTo Trial).
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 8, 2022 (Actual)
Primary Completion Date
March 2, 2024 (Anticipated)
Study Completion Date
March 2, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Respiratory Diseases, Mexico
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
Nowadays, no single drug is approved to treat rheumatoid arthritis-related interstitial lung disease (RA-ILD). The medical management of this clinical condition is empirical and controversial. There is preliminary data that tofacitinib may have a beneficial effect in treating RA-ILD. Tofacitinib may have a double role in treating RA-ILD: treat RA disease activity and an anti-fibrotic possible impact. Moreover, tofacitinib may be used as monotherapy for the treatment of rheumatoid arthritis (RA) This is a phase IIa clinical trial to evaluate the safety and tolerability of tofacitinib in RA-ILD patients.
Detailed Description
This is a phase 2 open-label study designed to evaluate the safety and tolerability of tofacitinib in RA-ILD patients. Patients who met the inclusion criteria of the study protocol will receive tofacitinib 5 mg BID for 12 months.
Objectives
Primary objectives:
To evaluate the safety and tolerability of tofacitinib 5 mg PO BID as monotherapy for managing RA-ILD in RA-ILD patients.
To evaluate the pulmonary function of patients treated with tofacitinib PO BID as monotherapy to manage RA-ILD in RA-ILD patients, at baseline, at three months of follow-up, at six months of follow-up, and one year of follow-up.
To estimate the efficacy of tofacitinib 5 mg PO BID as monotherapy for the management of RA-ILD, in RA-ILD patients, at three months of follow-up, at six months of follow-up, and at one year of follow-up, according to the ACR 20, 50, 70 response criteria, and the following disease activity scores index: DAS 28, CDAI and SDAI.
All the included patients will receive Tofacitinib in doses of 5 mg BID until the end of the protocol.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, Interstitial Lung Disease
Keywords
Rheumatoid Arthritis, Interstitial Lung Disease, Usual interstitial pneumonia, Tofacitinib, Rheumatoid Arthritis-related interstitial lung disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
This is a phase 2 open-label study designed to evaluate the safety and tolerability of tofacitinib in RA-ILD patients. Patients who met the inclusion criteria of the study protocol will receive tofacitinib 5 mg BID for 12 months.
Masking
None (Open Label)
Masking Description
This is an open-label study
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tofacitinib Arm
Arm Type
Experimental
Arm Description
Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months.
Intervention Type
Drug
Intervention Name(s)
Tofacitinib
Intervention Description
Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months.
Patients who met the inclusion criteria of the study protocol will received tofacitinib 5 mg BID for 12 months
Primary Outcome Measure Information:
Title
Incidence and severity of adverse events
Description
Adverse event: Any untoward medical occurrence in a subject being included in the trial, in which the event may not necessarily have a causal relationship with the treatment. Examples of adverse events are as follows: abnormal test findings, clinically significant symptoms and signs, hypersensitivity reactions, and progression or worsening of RA or RA-ILD.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Forced Vital Capacity (liters)
Description
Forced vital capacity (FVC) on spirometry, the data will be presented as percentages of predicted values, according to sex, age, height, and weight.
Time Frame
52 weeks
Title
Carbon monoxide diffusing capacity (DLCO) (mil/min/mmHg)
Description
The data will be presented as percentages of predicted values, according to sex, age, height, and weight.
Time Frame
52 weeks
Title
6 minutes walk test
Description
walked metters in 6 minutes
Time Frame
52 weeks
Title
Rheumatoid arthritis disease activity according to the simplified disease activity (SDAI) index.
Description
The SDAI index consists of the algebraic sum of the following items: tender joint count, swollen joint count, c-reactive protein, rheumatoid arthritis activity according to the patient, disease activity according to the attending physician.
Time Frame
52 weeks
Title
Rheumatoid arthritis disease activity according to the Disease Activity Score Index (DAS28)
Description
The DAS28 score is calculated with the tender joint count, swollen joint count, eritrosedimentation rate, patients' global health assesment aacording with the following formula DAS28 = ( 0.56 * sqr(TJC)) + (0.28 * sqr(SJC)) + ( 0.7 * ln(VSG)) + (0.014 * GH)
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients must fulfill ACR/EULAR 2010 RA classification criteria.
Patients must have an interstitial lung disease confirmed by a high-resolution computed tomography scan or a surgical lung biopsy. Nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphocytic pneumonia, and organized pneumonia, either by HRCT or surgical biopsy, will be included.
Patients must be 18 years of age or older.
There is no evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB).
Patients must discontinue using the non-permitted medications: leflunomide, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, and any biologic disease-modifying drug (bDMDARDs) such as anti-TNF therapy, rituximab, tocilizumab, etc. Patients must have a stable prednisone dose of ≤ 10 mg/ PO/day for at least three months.
All patients must have stable doses of prednisone during the last three months of follow-up, and the prednisone dose must be ≤ 10 mg/day. Patients without a prednisone history in the previous three months may also be included in the protocol.
Exclusion Criteria:
Seropositivity for the following infections: HIV, HBV, and HCV.
Absolute neutrophil count ≤ 1,200/L
Absolute platelet count ≤ 100,000 /L
Severe renal damage with GFR < 30 ml/min based on CKD-EPI formula.
AST or ALT greater than 1.5 times the upper limit of normal AST and ALT levels
Severe hepatic, hematologic, gastrointestinal, cardiac, and neurological disease may put the patient´s life at risk regardless of ILD severity.
Severe active infections at baseline evaluation, such as pneumonia, urinary tract infections, meningitis.
8 History of drug abuse or alcoholism. 9. History of any malignancy 10. Patients with an FVC < 40% of what is expected will be excluded from the study.
-
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jorge Rojas-Serrano, MD, PhD
Phone
+ 52 5554871700
Ext
5276
Email
jrojas@iner.gob.mx
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Estrada-Garrido, MD
Phone
+52 5554871700
Ext
5276
Email
estradagara@yahoo.com.mx
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Rojas-Serrano, MD, PhD
Organizational Affiliation
Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas
City
Mexico City
State/Province
Tlalpan
ZIP/Postal Code
14080
Country
Mexico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jorge Rojas-Serrano, MD, PhD
Phone
+ 52 5554871700
Ext
5276
Email
jrojas@iner.gob.mx
First Name & Middle Initial & Last Name & Degree
Andrea Estrada-Garrido, MD
Phone
+52 5554871700
Ext
5276
Email
estradagara@yahoo.com.mx
First Name & Middle Initial & Last Name & Degree
Mayra Mejia, MD
First Name & Middle Initial & Last Name & Degree
Heidegger Mateos-Toledo, MD
First Name & Middle Initial & Last Name & Degree
Andrea Estrada-Garrido, MD
First Name & Middle Initial & Last Name & Degree
Ramces Falfán-Valencia, PhD
First Name & Middle Initial & Last Name & Degree
Angel E. Vega-Sánchez, MD
First Name & Middle Initial & Last Name & Degree
Norma A. Téllez-Navarrete, MD, MsC
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We will share data, including data dictionaries and analytic code, after presenting the results of the study in a congress or the final publication of the clinical trial. The data will be shared only if a formal research proposal and our local IRB approves this.
IPD Sharing Time Frame
The data will be available after presenting the study results at an international congress or the final publication of the study.
IPD Sharing Access Criteria
A formal research proposal, including a research protocol, should be presented to the PI of the study to share the data. The research proposal has to be approved by our local IRB.
Citations:
PubMed Identifier
33976699
Citation
Vacchi C, Manfredi A, Cassone G, Cerri S, Della Casa G, Andrisani D, Salvarani C, Sebastiani M. Tofacitinib for the Treatment of Severe Interstitial Lung Disease Related to Rheumatoid Arthritis. Case Rep Med. 2021 Apr 22;2021:6652845. doi: 10.1155/2021/6652845. eCollection 2021.
Results Reference
background
PubMed Identifier
32826657
Citation
Citera G, Mysler E, Madariaga H, Cardiel MH, Castaneda O, Fischer A, Richette P, Chartrand S, Park JK, Strengholt S, Rivas JL, Thorat AV, Girard T, Kwok K, Wang L, Ponce de Leon D. Incidence Rates of Interstitial Lung Disease Events in Tofacitinib-Treated Rheumatoid Arthritis Patients: Post Hoc Analysis From 21 Clinical Trials. J Clin Rheumatol. 2021 Dec 1;27(8):e482-e490. doi: 10.1097/RHU.0000000000001552.
Results Reference
background
PubMed Identifier
30806708
Citation
Harigai M. Growing evidence of the safety of JAK inhibitors in patients with rheumatoid arthritis. Rheumatology (Oxford). 2019 Feb 1;58(Suppl 1):i34-i42. doi: 10.1093/rheumatology/key287.
Results Reference
background
Learn more about this trial
Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease.
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