Trial of Efficacy and Safety of MC0518 Versus Best Available Therapy in Participants With Steroid-Refractory Acute Graft Versus Host Disease

NCT06075706 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: MC-MSC.2/aGvHD2023-503952-28-00
• Study Type: interventional
• Target: 49
• Locations: 5 countries
• Sites: 36

Brief Summary

The purpose of this trial is the comparative evaluation of overall response rate (ORR) in paediatric participants with steroid-refractory acute graft-versus-host disease (SR-aGvHD) at Visit Day 28 after treatment with MC0518 or first used best available therapy (BAT).

Conditions

Steroid-refractory Acute Graft-versus-host Disease

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Overall Response (OR)

  OR is defined as complete response (CR) or partial response (PR) at Day 28 relative to acute graft-versus-host disease (aGvHD) status at baseline. CR is defined as resolution of aGvHD in all involved organs. PR is defined as improvement in 1 stage in at least 1 or more organs involved with aGvHD symptoms without progression in others.

  At Day 28

Secondary Outcomes (21)

• Number of Participants With Freedom From Treatment Failure (FFTF) Until 6 Months (Day 180)

  Up to 6 months (Day 180)

• Overall Survival (OS)

  Up to Month 24

• Number of Participants With aGvHD Response

  At Days 28, 60, 100 and 180

• Change From Baseline in aGvHD Grades

  Baseline, Days 8, 15, 22, 28, 60, 100 and 180

• Time to Response

  From the date of the first treatment administration to the date of the first response (CR or PR) (up to 5 years)

Study Arms (2)

MC0518

EXPERIMENTAL

Participants will be treated with intravenous infusions of MC0518 at a dose of 1 to 2\*10\^6 cells per kilogram (cells/kg) (based on body weight at the Screening Visit). Infusions will be administered once a week for 4 weeks (Visit Day 1, 8, 15, and 22). Participants with partial response (PR) on Day 28 will have 2 additional MC0518 infusions administered on Day 29 and 36.

Biological: MC0518

Best Available Therapy (BAT)

ACTIVE COMPARATOR

Participants will receive one of the following systemic BATs based on the Investigator's decision: extracorporeal photopheresis (ECP), anti-thymocyte globulin (ATG), etanercept, infliximab or ruxolitinib (RUX).

Biological: BAT

Interventions

MC0518 BIOLOGICAL

MC0518 will be intravenously infused immediately after thawing.

MC0518

BAT BIOLOGICAL

BAT including ECP, ATG, etanercept, infliximab or RUX will be administered based on Investigator's decision.

Best Available Therapy (BAT)

Eligibility Criteria

• Age: 28 Days - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participant had a previous allogeneic HSCT as indicated for non-malignant (including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies, and bone marrow failure syndromes) or hematological malignant disease or neuroblastoma.
• Participant has been clinically diagnosed with Grade II to IV aGvHD according to Harris et al. A biopsy of the involved organs with aGvHD is encouraged but not required.
• Participant has experienced failure of previous first-line aGvHD treatment (that is, SR-aGvHD), defined as:
• aGvHD progression within 3 to 5 days of therapy onset with \>=2 milligram per kilogram per day (mg/kg/day) of prednisone equivalent or
• failure to improve within 5 to 7 days of treatment initiation with \>=2 mg/kg/day of prednisone equivalent or
• incomplete response after greater than (\>) 28 days of immunosuppressive treatment including at least 5 days with \>=2 mg/kg/day of prednisone equivalent.
• Male or female participant who is \>=28 days and \<18 years of age and has a minimum body weight of 3.2 kilograms (kg) at the Screening Visit.
• Participant has an estimated life expectancy of \>28 days.
• Participant, if female and of childbearing potential, agrees to use a highly effective contraceptive measure starting at the Screening Visit and continuing throughout the entire trial period.
• Participant, if a fertile male, agrees to sexual abstinence or to use a condom during sexual activity with their female partner of childbearing potential or pregnant partner. Additionally, if their partner is a woman of childbearing potential (WOCBP), then their partner must use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period.
• A written informed consent of the participant's parent(s) / legal guardian(s) (and participant's assent, when applicable) has been obtained according to national regulations.

You may not qualify if:

• Participant has overt relapse or progression or persistence of the underlying disease.
• Participant has received the last HSCT for a solid tumor disease other than neuroblastoma.
• Participant has graft-versus-host disease overlap syndrome.
• Participant has received systemic first-line treatment for aGvHD other than steroids and a prophylaxis with other than calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, anti-thymocyte globulin, mycophenolate mofetil, methotrexate, abatacept, or cyclophosphamide. Note: In vitro or in vivo graft manipulation to prevent graft-versus-host disease (example, T-cell depletion) during HSCT is permitted. Restart of initial prophylaxis with calcineurin inhibitors, mammalian target of rapamycin inhibitors, or mycophenolate mofetil after aGvHD onset is permitted.
• Participant has received prior mesenchymal stromal cell (MSC) treatment, including MC0518/Obnitix®.
• Participant has a known pregnancy (as confirmed by a positive pregnancy test result at the Screening Visit) and / or is breastfeeding.
• Participant has a known hypersensitivity to MC0518 and / or its excipients (dimethyl sulfoxide, human serum albumin, isotonic sodium chloride solution).
• Participant has a known hypersensitivity or any contraindication to the Investigator's choice BAT (extracorporeal photopheresis, anti thymocyte globulin, etanercept, infliximab, or ruxolitinib) and / or its excipients. For a list of excipients please refer to the respective Summary of Product Characteristics.
• Participant has an underlying or current medical or psychiatric condition that, in the opinion of the Investigator, would interfere with the evaluation of the participant.
• Participant has an uncontrolled infection (examples, sepsis or multi-organ failure) including significant bacterial, fungal, viral, or parasitic infection requiring treatment.
• Participant has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit.

Sponsors & Collaborators

• medac GmbH: lead

Study Sites (36)

CHU de Bordeaux - Hopital des Enfants

Bordeaux, 33000, France

Location

CHU Grenoble Alpes - Hopital Couple Enfant (HCE)

La Tronche, 38700, France

Location

Centre Hospitalier Universitaire de Lille CHU Lille - Hopital Jeanne de Flandre HJF

Lille, 59037, France

Location

Institut d'Hematologie et d'Oncologie Pediatrique (IHOPe)

Lyon, 69373, France

Location

CHU de Marseille-Hopital de la Timone

Marseille, 13385, France

Location

Centre Hospitalier Regional Universitaire (CHRU) Montpellier - hopital Arnaud de Villeneuve

Montpellier, 34295, France

Location

CHU de Nantes - Hopital Mere Enfant

Nantes, 44093, France

Location

Hopital Robert Debre

Paris, 75019, France

Location

CHU de Rouen - Hopital Charles Nicolle

Rouen, 73038, France

Location

CHRU de Strasbourg - Hopital de Hautepierre

Strasbourg, 67000, France

Location

CHRU Nancy, Hopitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Uniklinik RWTH Aachen, Klinik fur Kinder- und Jugendmedizin

Aachen, 52074, Germany

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Klinikum der Johann Wolfgang Goethe

Frankfurt, 60596, Germany

Location

Universitaetsklinikum Freiburg - Zentrum fuer Kinder- und Jugendmedizin (ZKJ)

Freiburg im Breisgau, 79106, Germany

Location

Justus-Liebig-Universitaet Giessen

Giessen, 35392, Germany

Location

Medizinische Hochschule Hannover MHH

Hanover, 30625, Germany

Location

Department of Pediatrics, Jena University Hospital

Jena, 7747, Germany

Location

Universitaetsklinikum Leipzig - Abteilung fuer Paediatrische Onkologie, Haematologie und Haemostaseologie

Leipzig, 4103, Germany

Location

Universitaetsklinikum Muenster (UKM) - Klinik fuer Kinder- und Jugendmedizin - Paediatrische Haematologie und Onkologie

Münster, 48129, Germany

Location

IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S.Orsola Malpighi

Bologna, 40138, Italy

Location

Pediatric Clinic Onco Hematology San Gerardo Hospital

Monza, 20052, Italy

Location

U.O.C. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Hematology and Cellular Therapy Ospedale Bambino Gesu

Rome, 165, Italy

Location

A.O.U. Citta della Salute e della Scienza di Torino Ospedale Infantile Regina Margherita

Turin, 10126, Italy

Location

Department of Pediatric Hematology, Oncology and BMT, Wroclaw Medical University

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Dzieciecy Szpital Kliniczny im. A.Gebali w Lublinie

Lublin, 20-093, Poland

Location

Szpital Kliniczny im. Karola Jonschera UM

Poznan, 60-572, Poland

Location

Hospital Niño Jesus

Madrid, Madrid, 28009, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario Vall dHebron

Barcelona, 8035, Spain

Location

Hospital Sant Joan de Deu Barcelona (HSJDB)

Barcelona, 8950, Spain

Location

Hospital Infantil Universitario La Paz

Madrid, 28046, Spain

Location

Instituto de Investigacion Biomedica de Malaga IBIMA - sede Hospital Regional Universitario de Malaga HRUM Hospital Carlos Haya

Málaga, 29011, Spain

Location

Instituto Murciano de Investigacion Biosanitaria (IMIB) Virgen de la Arrixaca

Murcia, 30120, Spain

Location

Hospital Universitari I politecnic La Fe Jose

Valencia, 46026, Spain

Location

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2023
• First Posted: October 10, 2023
• Study Start: November 13, 2023
• Primary Completion: February 11, 2026
• Study Completion (Estimated): June 1, 2031
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

FR (11); PL (3); ES (8); DE (9); IT (5)