Clinical trial NCT05246293: Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease.
Official title: Safety and Tolerability of Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease (RAILDTo Trial).
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Interstitial Lung Disease
Keywords: Rheumatoid Arthritis
Interstitial Lung Disease
Usual interstitial pneumonia
Tofacitinib
Rheumatoid Arthritis-related interstitial lung disease
Lead sponsor: National Institute of Respiratory Diseases, Mexico
Sponsor class: OTHER_GOV
First posted: 2022-02-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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:

1. To evaluate the safety and tolerability of tofacitinib 5 mg PO BID as monotherapy for managing RA-ILD in RA-ILD patients.
2. 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.
3. 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.

Eligibility criteria: Inclusion Criteria:

1. Patients must fulfill ACR/EULAR 2010 RA classification criteria.
2. 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.
3. Patients must be 18 years of age or older.
4. There is no evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB).
5. 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.
6. 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:

1. Seropositivity for the following infections: HIV, HBV, and HCV.
2. Absolute neutrophil count ≤ 1,200/L
3. Absolute platelet count ≤ 100,000 /L
4. Severe renal damage with GFR \< 30 ml/min based on CKD-EPI formula.
5. AST or ALT greater than 1.5 times the upper limit of normal AST and ALT levels
6. Severe hepatic, hematologic, gastrointestinal, cardiac, and neurological disease may put the patient´s life at risk regardless of ILD severity.
7. 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.

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Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 52 weeks
Secondary outcomes:
measure: Forced Vital Capacity (liters)
timeFrame: 52 weeks
measure: Carbon monoxide diffusing capacity (DLCO) (mil/min/mmHg)
timeFrame: 52 weeks
measure: 6 minutes walk test
timeFrame: 52 weeks
measure: Rheumatoid arthritis disease activity according to the simplified disease activity (SDAI) index.
timeFrame: 52 weeks
measure: Rheumatoid arthritis disease activity according to the Disease Activity Score Index (DAS28)
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas
state: Tlalpan
Study officials:
affiliation: Instituto Nacional de Enfermedades Respiratorias, Ismael Cosío Villegas
name: Jorge Rojas-Serrano, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.