An experimental study in adults and adolescents who underwent stem cell transplantation and developed a Graft versus Host Disease after steroid treatment; to test the safety, tolerability and the effects of treatment with mesenchymal stromal cells MC0518

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medac Gesellschaft fuer klinische Spezialprapaerate mbH

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

22 Jul 2020 → ongoing

Decision date (initial)

2024-05-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

medac Gesellschaft für klinische Spezialpräparate mbH, Germany

External identifiers

EU CT number

2023-505737-26-00

EudraCT number

2019-001462-15

WHO UTN

U1111-1303-8595

ClinicalTrials.gov

NCT04629833

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Safety, Therapy

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 objectives 4

1. 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)
2. Compare the efficacy of MC0518 and BAT in further secondary long-term efficacy endpoints and response to treatment
3. Investigate the safety of MC0518
4. Compare health-related quality of life (HRQoL) when treated with MC0518 compared with BAT

Conditions and MedDRA coding

Steroid refractory Acute Graft versus host Disease

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002706-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 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, irrespective of human leukocyte antigen match
2. Subject has been clinically diagnosed with Grade II to IV aGvHD at the Screening Visit.
3. 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.
4. Male or female subject who is ≥ 12 years of age and ≥ 15 kg at the Screening Visit.
5. Subject has an estimated life expectancy > 28 days at the Screening Visit.
6. 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.
7. 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 the definition of fertile men and a complete list of highly effective contraceptive measures are included in an appendix to the protocol.
8. 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.

Exclusion criteria 6

1. Subject has overt relapse or progression or persistence of the underlying disease at the Screening Visit.
2. Subject has received the last HSCT for a solid tumour disease.
3. Subject has GvHD overlap syndrome at the Screening Visit.
4. 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. 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.
5. Subject has a known pregnancy (as confirmed by a positive pregnancy test at the Screening Visit) and or is breastfeeding at the Screening Visit.
6. Subject has received treatment with any other investigational agent within 30 days or 5 half-lives (whichever is longer) before the Screening Visit.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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).
2. OS until Visit Month 24, defined as the time from the date of randomisation to the date of death due to any cause

Secondary endpoints 15

1. 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.
2. 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.
3. 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
4. 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)
5. 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.
6. Best OR until Visit Day 28 defined as the achievement of an OR at any time point up to and including Visit Day 28
7. Cumulative dose of steroids given for SR-aGvHD from baseline until Visit Day 60 and until Visit Month 24
8. Incidence of and time to cGvHD from Visit Day 60 until Visit Month 24
9. Incidence of graft failure (GF) from baseline until Visit Month 24
10. Incidence of and time to relapse or progression in subjects with underlying malignant disease from randomisation until Visit Month 24
11. 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.
12. 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.
13. The incidence and severity of all adverse events (AEs) until Visit Day 60 or until 30 days after last administration of trial treatment, whichever is later. Thereafter, the incidence of adverse reactions (ARs) will be documented until Visit Month 24.
14. Performance score (Karnofsky / Lansky scale) at Visit Day 8, Visit Day 15, Visit Day 22, Visit Day 28, Visit Day 60, and Visit Day 100 in comparison to the baseline.
15. HRQoL measures: EuroQol 5D 5L (EQ 5D 5L) and the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACTBMT) at Visit Day 28, Visit Day 60, Visit Day 100, and Visit Day 180 in comparison to the baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medac Gesellschaft fuer klinische Spezialprapaerate mbH

Sponsor organisation

Medac Gesellschaft fuer klinische Spezialprapaerate mbH

Address

Theaterstrasse 6

City

Wedel

Postcode

22880

Country

Germany

Scientific contact point

Organisation

Medac Gesellschaft fuer klinische Spezialprapaerate mbH

Contact name

Clinical Trial Information

Public contact point

Organisation

Medac Gesellschaft fuer klinische Spezialprapaerate mbH

Contact name

Clinical Trial Information

Third parties 7

Locations

4 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 40 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications