3T Therapy in the Treatment of MDA5-positive Dermatomyositis

A Single-centric Prospective Single-arm Study of 3T Therapy in the Treatment of MDA5-positive Dermatomyositis

The goal of this clinical trial is to learn if a combination of tacrolimus, tafocitinib and thalidomide (3T therapy) works to treat severe MDA5 positive dermatomyositis in adults. It will also learn about the safety of 3T therapy. The main questions it aims to answer are:

Does 3T therapy prolong the overall survival time of MDA5 positive dermatomyositis? What medical problems do participants have when taking 3T therapy?

Participants will:

Take 3T therapy every day for 12 months Visit the clinic once every 2 weeks for checkups and tests

Study Overview

• Status: Enrolling by invitation
• Conditions: Dermatomyositis
• Intervention / Treatment: Drug: Tofacitinib 5 MG

• Study Type: Interventional
• Enrollment (Estimated): 133
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Zhejiang University School of Medicine Second Affiliated Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 or above at the time of screening

• Diagnosis of MDA5-positive dermatomyositis (EULAR/ACR) during screening, and the following 3 items are met at the same time:

  1. The MDA5 titer during screening is ++ or +++;
  2. Mild or above decrease in pulmonary diffusing function at screening and baseline;
  3. Interstitial extravasation seen on chest CT at screening and baseline
• Agree to receive highly effective contraception or sterilized
• Subjects are willing and able to comply with study visits and related procedures
• Subjects have the ability to understand the research requirements and procedures, voluntarily participate in clinical trials and sign the ICF

Exclusion Criteria:

• Have received any drug in 3T treatment in the past, but had poor response (including treatment failure or unacceptable treatment-related adverse reactions)
• Have received lenalidomide, cyclosporine, or other highly selective or pan-selective JAK inhibitors such as lenalidomide or cyclosporine or other highly selective or pan-selective JAK inhibitors such as baricitinib within 2 weeks before visit D1 or within 5 drug half-lives (if known) agent.
• Have received treatment with an immune cell depleting agent (such as rituximab) within 6 months before the D1 visit.
• Have received any investigational drug/treatment within 4 weeks or 5 drug half-lives (if known) before visit D1, whichever is longer.
• Known or suspected history of immunosuppression/deficiency (including but not limited to invasive opportunistic infections such as aspergillosis, coccidioidomycosis, histoplasmosis, AIDS, listeriosis, even if the infection has resolved) within 6 months prior to visit D1, or there are unusually frequent recurring or persistent infections.
• There is a history of malignant tumors within 5 years before the D1 visit (except for completely cured cervical carcinoma in situ or non-metastatic cutaneous squamous cell carcinoma or basal cell carcinoma or thyroid malignant tumors or other malignant tumors considered by the researcher to be amenable to 3T treatment).
• Positive hepatitis B surface antigen (HBsAg) during screening; or positive hepatitis B core antibody (HBcAb) and positive HBV-DNA; or positive hepatitis C antibody and positive HCV ribonucleic acid (RNA) polymerase chain reaction; or human immune HIV-deficiency virus (HIV) serology was positive.
• Subjects with active tuberculosis, latent tuberculosis, or a history of non-tuberculous mycobacterial infection at the time of screening.
• Have a history of systemic hypersensitivity reaction to any drug or matrix or excipient in 3T therapy.
• Have been vaccinated within 12 weeks before the D1 visit, or plan to receive a live (attenuated) vaccine during the study.
• Pregnant or lactating women, or subjects who plan to become pregnant or lactating during the study.
• Any other circumstances in which the researcher determines that it is not appropriate to participate in this study

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: 3T therapy arm; This is a single arm experiment	Drug: Tofacitinib 5 MG; Tofacitinib 5mg BID+thalidomide 50mg BID+tacrolimus 0.1mg/kg QD per oral; Other Names: tacrolimus; thalidomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival rate	The overall survival rate at the end of observation	26 weeks
Overall TE incidence	The overall treatment associated adverse effects incidence during the clinical trial	26 weeks

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2024
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 31, 2024
• First Posted (Actual): June 3, 2024

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: effectiveness; dermatomyositis; MDA5; 3T therapy
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Polymyositis; Myositis; Dermatomyositis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Leprostatic Agents; Calcineurin Inhibitors; Janus Kinase Inhibitors; Thalidomide; Tacrolimus; Tofacitinib
• Other Study ID Numbers: IRB2024-0285

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No