3T Therapy in the Treatment of MDA5-positive Dermatomyositis

Launched by SECOND AFFILIATED HOSPITAL, SCHOOL OF MEDICINE, ZHEJIANG UNIVERSITY · May 31, 2024

Keywords

ClinConnect Summary

This is a Phase 4, single-arm interventional study testing a combination called 3T therapy for adults with a severe form of dermatomyositis that is positive for the MDA5 antibody. Participants take three drugs—tofacitinib, tacrolimus, and thalidomide—every day for about a year, with clinic visits every two weeks for tests and checkups. The study will enroll about 133 people at Zhejiang University School of Medicine, Second Affiliated Hospital in Hangzhou, China. The main goals are to see how many participants are still alive at about 26 weeks and how often treatment-related side effects occur during the trial.

To be eligible, adults must be 18 or older and have MDA5-positive dermatomyositis, plus certain lung findings shown on tests and imaging (a mild or greater drop in lung function and chest CT changes). They must agree to use effective contraception and be able to follow the study visits. People who have previously tried 3T therapy with a poor response, or who have certain infections or immune problems, recent cancer, active hepatitis B/C or HIV, active tuberculosis, pregnancy, or other safety concerns, are not eligible. The study is enrolling by invitation and is based at the Second Affiliated Hospital, Zhejiang University.

Gender

ALL

Eligibility criteria

• 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