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

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.

FFTF is defined as the time from the date of randomization to the date of the event. An event is defined as death, relapse or progression of the underlying disease, or addition or change to any further systemic immunosuppressive aGvHD therapy.

Overall survival is defined as the time from randomization to the date of death due to any cause.

aGvHD response will be categorized as OR (CR + PR), CR, PR, and NR. NR is defined as the absence of CR or PR.

aGvHD grades: Grade 0- no organ involvement (that is, Stage 0 skin, Stage 0 liver, and Stage 0 gastrointestinal [GI]); Grade I-Stage 1 - 2 skin without liver/GI involvement; Grade II- Stage 3 skin and / or Stage 1 liver and / or Stage 1 GI; Grade III- Stage 2 - 3 liver and / or Stage 2 - 3 GI; Grade IV- Stage 4 skin and / or Stage 4 liver and/or Stage 4 GI.

Time to response is defined as the time from the date of the first treatment administration to the date of response (CR or PR).

Duration is defined as the time from the date of the first OR (CR or PR) to the date of aGvHD assessed as NR compared to the baseline assessment, or the date of addition of or change to any further systemic aGvHD therapy (except changes in steroid treatment), in responders.

Best OR is defined as the achievement of an OR at any time point up to and including Day 28.

The cumulative dose of steroids given for SR-aGvHD per kg of body weight from the date of the first treatment administration until Day 28, Day 60, and until Visit Month 24 will be analyzed.

Number of participants with cGvHD will be reported.

Time to cGvHD is defined as the time between the last day of hematopoietic stem cell transplantation (HSCT) to the first episode of cGvHD.

Number of participants with GF will be reported.

Number of participants with relapse or progression in participants with underlying malignant disease will be reported.

Time to relapse or progression is defined as the time from the date of randomization to the date of relapse or progression until Month 24.

EFS is defined as the time from the date of randomization to the date of the event. An event is defined as GF, relapse or progression of the underlying disease, or death due to any cause.

NRM is defined as the time from the date of randomization to the date of the event. An event is defined as death without previous relapse or progression of the underlying disease.

An AE is defined as any untoward medical occurrence in a trial participant administered a trial treatment that does not necessarily have a causal relationship with this trial treatment.

An AR is defined as all noxious and unintended responses to a trial treatment related to any dose administered / procedure performed. Severity will be graded based on Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening consequences; urgent intervention indicated; Grade 4- Death related to the AE.

The Karnofsky performance score (KPS), which is reported on an ordinal scale from 0 to 100, provides a rough measure of the participant's (recipient age greater than or equal to [>=] 16 years) well-being, including their ability to conduct activities of daily living and functional capacity. Higher score indicates normal, no complaints and no evidence of disease.

A Lansky score (recipient age >=1 year and less than [<] 16 years) will be recorded pre-treatment and measured serially at regular intervals after treatment. The score is a standard performance score that measures overall function of the child with a scale range from 0 to 100. Higher score indicates full activeness.

The PedsQL Generic Core Scales instrument is a standardized, established, and validated questionnaire in pediatric populations that systematically assesses the participants' and parents' / legal guardians' perceptions of health-related quality of life (HRQoL). The Generic Core Scales module consists of 23 items measuring the core dimensions of health on physical, emotional, social, and school functioning that can be used for self- and proxy-reports in age groups ranging from 2 to 18 years (child self-report ages: 5 to 7, 8 to 12, 13 to 18; parent-proxy report ages: 2 to 4, 5 to 7, 8 to 12, 13 to 18). The scores of this questionnaire range from 0 to 100 , where higher scores indicate better HRQoL.

The PedsQL™ Stem Cell Transplant Module is a disease-specific module of the PedsQL™ for toddlers (2 to 4 years of age), young children (5 to 7 years of age), children (8 to 12 years of age), and adolescents (13 to 18 years of age) and was designed to measure the quality of life in participants undergoing stem cell transplantation. It consists of the following HRQoL domains: pain and hurt, fatigue / sleeping problems / weakness, nausea, worry / anxiety about disease / treatment, nutritional problems, neurocognitive problems, communication about disease / treatment, loneliness, physical functioning and additional somatic complaints (pruritus, skin inflammation, oral problems, eyes or breathing) including patients' and parents' assessment. The scores of this disease-specific module of the PedsQL™ range from 0 to 100, where higher scores indicate better HRQoL.