A Prospective Study of Madecassoside Tablets in Sclerotic Chronic Graft-versus-Host Disease After Allo-HSCT

A Prospective, Multicenter, Single-Arm Phase 2 Study of Madecassoside Tablets Combined With Standard Therapy for Sclerotic Chronic Graft-versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Sclerotic chronic graft-versus-host disease (scl-cGVHD) is a severe subtype of chronic GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by skin sclerosis, fascial involvement, and restricted joint mobility, leading to substantial functional impairment and reduced quality of life. Current standard therapies, including corticosteroids and other immunosuppressive agents, have limited efficacy in patients with refractory or steroid-dependent disease.

Madecassoside tablets, a standardized extract of Centella asiatica, have demonstrated anti-inflammatory and anti-fibrotic properties in previous studies and may provide therapeutic benefit in fibrotic diseases.

This study is a prospective, multicenter, single-arm phase 2 clinical trial designed to evaluate the efficacy and safety of madecassoside tablets combined with standard therapy in patients with scl-cGVHD after allo-HSCT. Eligible participants will receive oral madecassoside tablets (0.2 g three times daily) in addition to standard treatment for 6 months. Clinical assessments will be performed at baseline and at weeks 4, 8, 12, and 24.

The primary endpoint is the improvement rate of skin and/or joint/fascia NIH cGVHD scores at 6 months according to the 2014 NIH consensus criteria. Secondary endpoints include overall cGVHD response rate, failure-free survival, non-relapse mortality, corticosteroid dose reduction, patient-reported outcomes, and safety assessments. Peripheral blood samples will also be collected to explore changes in inflammatory cytokines and lymphocyte subsets during treatment.

Study Overview

• Status: Recruiting
• Conditions: Graft vs Host Disease; Chronic Graft-Versus-Host Disease
• Intervention / Treatment: Drug: Madecassoside Tablets; Drug: Standard Therapy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: wei MD, PhD; Phone Number: +86 027-85726003; Email: shiwei076@hust.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Wei Shi, M.D.; Phone Number: +86 027-85726003; Email: shiwei076@hust.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Ability to understand and willingness to sign written informed consent;
2. Age 14 to 65 years;
3. Diagnosis of sclerotic chronic graft-versus-host disease (scl-cGVHD) according to the 2014 NIH consensus criteria, including superficial or deep skin sclerosis, fasciitis, or restricted joint mobility;

4. Prior treatment history meeting at least one of the following:

   • Received systemic corticosteroid therapy for ≥12 months and at least 1 additional systemic therapy; OR
   • Received corticosteroid therapy and at least 2 additional systemic therapies;
5. Karnofsky Performance Status (KPS) score ≥60;
6. Absolute neutrophil count >1,000/μL;
7. Platelet count ≥50,000/μL.

Exclusion Criteria:

• 1. Total bilirubin >1.5 times the upper limit of normal; 2. Creatinine clearance <30 mL/min; 3. Uncontrolled infection; 4. Uncontrolled cardiovascular or pulmonary disease; 5. Any clinical condition that, in the investigator's judgment, makes the participant unsuitable for study participation.

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: Experimental: Madecassoside Tablets Plus Standard Therapy

Drug: Madecassoside Tablets; Madecassoside tablets will be administered orally at a dose of 0.2 g (2 tablets) three times daily for 6 months in combination with standard therapy.; Drug: Standard Therapy; Standard therapy may include corticosteroids, calcineurin inhibitors, ruxolitinib, belumosudil, topical medications, and supportive care according to institutional guidelines and physician discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Skin and/or Joint/Fascia NIH cGVHD Scores	The proportion of participants achieving complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) in skin and/or joint/fascia manifestations according to the 2014 NIH chronic graft-versus-host disease response criteria after 6 months of treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall cGVHD Response Rate	Overall response rate of chronic graft-versus-host disease based on the 2014 NIH response criteria.	6 months
Failure-Free Survival	Failure-free survival defined as survival without relapse, non-relapse mortality, or addition of new systemic therapy.	2 years
Non-Relapse Mortality	Incidence of death without relapse of the underlying disease during follow-up.	2 years
Corticosteroid Dose Reduction	Proportion of participants achieving at least 50% reduction or discontinuation of corticosteroid therapy.	6 months
Patient-Reported Outcomes	Changes in patient-reported outcomes including Lee Symptom Scale (LSS), Scleroderma Health Assessment Questionnaire (SHAQ), and Photographic Range of Motion (P-ROM) scores.	Baseline to 6 months
Traditional Chinese Medicine Symptom Score	Changes in Traditional Chinese Medicine symptom scores during treatment.	Baseline to 6 months
Safety and Adverse Events	Incidence and severity of adverse events assessed according to CTCAE version 5.0.	Up to 2 years

Collaborators and Investigators

• Sponsor: WeiShi

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 26, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organizing Pneumonia; Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchiolitis Obliterans Syndrome; Graft vs Host Disease; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care; madecassoside
• Other Study ID Numbers: OMD-HSCT-20250817

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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