Steroid refractory Acute Graft versus host Disease MedDRA version: 27.0 Level: PT Classification code 10066260 Term: Acute graft versus host disease System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: MC0518 30 Mio cells/ 30ml
Product Code: MC0518
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: Human allogeneic bone marrow derived mesenchymal stromal cells, ex-vivo e
Sponsors
medac Gesellschaft für klinische Spezialpräparate mbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject had a previous allogeneic HSCT as indicated for non-malignant (including inborn errors of metabolism, primary immunodeficiencies, haemoglobinopathies, and bone marrow failure syndromes) or haematological malignant disease - Subject has been clinically diagnosed with Grade II to IV aGvHD at the Screening Visit. - Subject has experienced failure of previous first line aGvHD treatment (ie, SR aGvHD), defined as: a. aGvHD progression within 3 to 5 days of therapy onset with = 2 mg/kg/day of prednisone equivalent or b. failure to improve within 5 to 7 days of treatment initiation with = 2 mg/kg/day of prednisone equivalent or c. incomplete response after > 28 days of immunosuppressive treatment including at least 5 days with = 2 mg/kg/day of prednisone equivalent. -Male or female subject who is = 12 years of age and = 15 kg at the Screening Visit. -Subject has an estimated life expectancy > 28 days at the Screening Visit (compliance to be re-confirmed at the Baseline Visit). -Subject, 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. The definition of women of childbearing potential (WOCBP) and a complete list of highly effective contraceptive measures .are included in an appendix to the protocol. -Subject, 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 WOCBP, then their partner has to use an additional highly effective contraceptive method during sexual activity starting at the Screening Visit and continuing throughout the entire trial period. For theThe definition of fertile men and a complete list of highly effective contraceptive measures are included in an appendix to the protocol. -Subject or parent(s) / legal guardian(s) have read, understood, and signed the informed consent form (and informed assent form, if applicable) according to national regulations. Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Subject has overt relapse or progression or persistence of the underlying disease at the Screening Visit. - Subject has received the last HSCT for a solid tumour disease. - Subject has GvHD overlap syndrome at the Screening Visit. - Subject 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 (ATG), mycophenolate mofetil (MMF), methotrexate (MTX), and or cyclophosphamide before the Screening Visit (compliance to be re-confirmed at the Baseline Visit). Please Note: In vitro or in vivo graft manipulation to prevent GvHD (eg, T-cell depletion) during HSCT is permitted. Restart of initial prophylaxis with calcineurin inhibitors or mTOR inhibitors after aGvHD onset is permitted. - Subject has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit. - Subject has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit (compliance to be confirmed for the period between the Screening Visit and the Baseline Visit at the Baseline Visit).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to demonstrate the superiority of MC0518 compared to the first used Best Available Therapy (BAT) with respect to ORR in adult and adolescent subjects with SR aGvHD at Visit Day 28. and/or to Demonstrate the superiority of MC0518 compared to the first used BAT with respect to overall survival (OS) in adult and adolescent subjects with SR aGVHD until Visit Month 24. ;Secondary Objective: Demonstrate the superiority of MC0518 compared with the first used BAT with respect to freedom from treatment failure (FFTF) as defined by the absence of death, malignancy relapse or progression, or addition or change to any further systemic aGvHD immunosuppressive therapy within 6 months from the date of randomisation up to the date of the event and before the diagnosis of chronic graft versus host disease (cGvHD) - Compare the efficacy of MC0518 and BAT in further secondary longterm efficacy endpoints and response to treatment - Investigate the safety of MC0518 - Compare health related quality of life (HRQoL) when treated with MC0518 compared with BAT -Collect data from resource utilisation and HRQoL assessments for economic analyses and health technology assessment (HTA) submissions;Primary end point(s): Overall response (OR) as defined by complete response (CR) or partial response (PR) at Visit Day 28 relative to aGvHD status at baseline (Visit Day 1 before the first treatment). CR is defined as resolution of aGvHD in all involved organs. PR is defined as improvement in at least 1 stage in 1 or more organs involved with aGvHD symptoms without progression in others. No response (NR) is defined as the absence of CR or PR. Death before Visit Day 28 will be considered as NR. The addition or change to any further systemic therapy after MC0518 / first used BAT before Visit Day 28 will be considered as NR. OS until Visit Month 24, defined as the time from the date of randomisation to the date of death due to any cause.;Timepoint(s) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - FFTF until 6 months, defined as the time from the date of randomisation 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. The diagnosis of cGvHD is considered to be a competing event. - aGvHD response at Visit Day 28 assessed by CR, PR, and NR and at Visit Day 60, Visit Day 100, and Visit Day 180 assessed by OR, CR, PR, and NR relative to baseline. - Change of aGvHD grade at Visit Day 8, Visit Day 15, Visit Day 22, Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 relative to baseline - Time to response, defined as the time from the date of the first treatment administration to the date of the first response (CR or PR) - Duration of the response until Visit Month 24, defined as the time from the date of the first OR (CR or PR) to the date of aGvHD assessed as NR compared with the baseline assessment, or the date of addition or change to any further systemic aGvHD therapy, in responders. - Best OR until Visit Day 28 defined as the achievement of an OR at any time point up to and including Visit Day 28 - Cumulative dose of steroids given for SR-aGvHD from baseline until Visit Day 60 and until Visit Month 24 - Incidence of and time to cGvHD from Visit Day 60 until Visit Month 24 - Incidence of graft failure (GF) from baseline until Visit Month 24 - Incidence of and time to relapse or progression in subjects with underlying malignant disease from randomisation until Visit Month 24 - Event free survival until Visit Month 24, defined as the time from the date of randomisation 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. - Non-relapse mortality (NRM) until Visit Month 24, defined as the time from the date of randomisation to the date of the event. An event is defined as death without previous relapse or progre | — |
Countries
France, Germany, Poland, Sweden
Contacts
Public ContactDmitrii Tkachenko
Syneos Health Germany GmbH
Outcome results
None listed