Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease.

NCT05246293 | Unknown Phase 2 FDA Drug

• 1 other identifier: C17-21
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis; Interstitial Lung Disease

Keywords

Rheumatoid Arthritis; Interstitial Lung Disease; Usual interstitial pneumonia; Tofacitinib; Rheumatoid Arthritis-related interstitial lung disease

Outcome Measures

Primary Outcomes (1)

• 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.

  52 weeks

Secondary Outcomes (5)

• Forced Vital Capacity (liters)

  52 weeks

• Carbon monoxide diffusing capacity (DLCO) (mil/min/mmHg)

  52 weeks

• 6 minutes walk test

  52 weeks

• Rheumatoid arthritis disease activity according to the simplified disease activity (SDAI) index.

  52 weeks

• Rheumatoid arthritis disease activity according to the Disease Activity Score Index (DAS28)

  52 weeks

Study Arms (1)

Tofacitinib Arm

EXPERIMENTAL

Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months.

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

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

Tofacitinib Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Institute of Respiratory Diseases, Mexico: lead

Study Sites (1)

Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas

Mexico City, Tlalpan, 14080, Mexico

RECRUITING

Related Publications (3)

• 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.

  PMID: 33976699 BACKGROUND

• 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.

  PMID: 32826657 BACKGROUND

• 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.

  PMID: 30806708 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Lung Diseases, Interstitial; Idiopathic Pulmonary Fibrosis

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lung Diseases; Respiratory Tract Diseases; Pulmonary Fibrosis

Study Officials

• Jorge Rojas-Serrano, MD, PhD

  Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jorge Rojas-Serrano, MD, PhD

CONTACT

+ 52 5554871700; jrojas@iner.gob.mx

Andrea Estrada-Garrido, MD

CONTACT

+52 5554871700; estradagara@yahoo.com.mx

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 17, 2022
• First Posted: February 18, 2022
• Study Start: August 8, 2022
• Primary Completion: March 2, 2024
• Study Completion: March 2, 2025
• Last Updated: April 27, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available after presenting the study results at an international congress or the final publication of the study.
• 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.

Locations

ME (1)