The Efficacy and Safety of Tofacitinib in Patients With Glucocorticoid Resistant ICIs-related Myocarditis

The Efficacy and Safety of Tofacitinib in Patients With Glucocorticoid Resistant ICIs-related Myocarditis: a Single-arm, Prospective, Phase 2 Trial

The efficacy and safety of Tofacitinib in patients with glucocorticoid resistant ICIs-related myocarditis: a single-arm, prospective, phase 2 trial

Study Overview

• Status: Not yet recruiting
• Conditions: Glucocorticoid Resistant ICIs-related Myocarditis
• Intervention / Treatment: Drug: Tofacitinib 5 MG BID

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Wang; Phone Number: +86-21-64041990; Email: wang.yan@zs-hospital.sh.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old
2. Patients treated with ICI immunotherapy (monotherapy or combination), including anti-PD1, anti-PDL1, anti-CTLA4; and including any type of cancer (even those in which ICI is not currently approved by regulatory)
3. Definite, probable or possible ICI-induced myocarditis according to the diagnostic criteria of the most recent expert consensus recommendations (e.g27, to be updated with any new recommendations to be published)
4. corticosteroid-resistant ICI-myocarditis: Corticosteroid-resistant ICI-myocarditis is defined by the absence of decrease in troponin levels or the appearance/persistence of severity criteria despite receiving prednisone dose ≥0.5 mg/kg/day for ≥2 days.
5. Signature of informed consent before any trial procedure from the patient or legal representative or the close relative
6. Patients covered by social security regimen (excepting AME)
7. Withhold of ICI

Exclusion Criteria:

1. Untreated and/or uncontrolled bacterial, fungal, or viral infection Pregnancy, breast-feeding or planning to become pregnant during the study period
2. For women of childbearing age, lack of effective contraception throughout the duration of participation in the study
3. Being treated with tofacitinib within 3 months prior to inclusion Known hypersensitivity to abatacept or belatacept
4. Being treated with anti-thymoglobulin, or alemtuzumab within 6 weeks of the first scheduled dose of abatacept
5. Patient participating to another interventional study (RIPH 1 only) People under legal protection measure (tutorship, curatorship or safeguard measures)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tofacitinib; Tofacitinib in patients with glucocorticoid resistant ICIs-related myocarditis	Drug: Tofacitinib 5 MG BID; Tofacitinib 5 MG BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality within three months	All-cause mortality within three months	The first three months after tofacitinib administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality within six months	All-cause mortality within six months	The firs six months after tofacitinib administration
Progression-free survival	Progression-free survival	From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months
Overall survival	Overall survival	From date of enrollment until the date of death from any cause, assessed up to 24 months"
Safety and tolerability based on incidence of treatment-emergent adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): November 30, 2025
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: November 23, 2023
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 26, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Myocarditis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: ZSLCYJ202353

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No