EvAluation of the efficacy of MaaT013 as salvage theRapy in acute GVHD patiEntS with gastrointestinal involvement, refractory to ruxolitinib; a multi-center open-label phase III trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

MaaT PHARMA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

12 Jan 2022 → 24 Sep 2025

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

MaaT Pharma

External identifiers

EU CT number

2024-513023-17-00

EudraCT number

2021-001841-11

ClinicalTrials.gov

NCT04769895

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To evaluate the efficacy of MaaT013 assessed by the overall response rate (ORR) of gastrointestinal (GI) acute graft-versus-host disease (aGVHD) response at day 28 (D28).

Secondary objectives 13

1. To evaluate MaaT013 Safety
2. To evaluate ORR for GI at D56 and M3
3. To evaluate ORR for all organs at D28, D56 and M3
4. To evaluate the best ORR (for GI and all organs) achieved between D0 and D28
5. To assess duration of response
6. To assess overall survival (OS)
7. To assess progression-free survival (PFS)
8. To assess time to progression
9. To assess steroid-free survival
10. To evaluate the frequency of patients that tapered off CS
11. To measure the incidence of chronic GvHD
12. To evaluate changes in patient reported outcomes (PROs)
13. To evaluate MaaT013 activity on immune markers

Conditions and MedDRA coding

Treatment of acute graft-versus host disease (aGvHD) to the gastrointestinal (GI) tract of patients who are resistant or intolerant to ruxolitinib.

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Age ≥ 18 years old
2. Allo-HSCT with any type of donor, stem cell source, GvHD prophylaxis or conditioning regimen.
3. Acute GvHD episode with GI involvement per MAGIC guidelines (= grades II to IV), with or without involvement of other organs (Harris et al. 2016).
4. Patients resistant to steroids AND either resistant to OR with intolerance to ruxolitinib (intolerant patients: who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib): Resistance to steroids is defined as any of the following: - Lack of improvement (i.e., no decrease in stage in at least 1 involved organ system) after ≥ 5 days of treatment with CS at 2mg/kg/d methylprednisolone equivalent dose, - Progression (i.e., increase in any organ system or any new organ involvement) after ≥ 3 days of treatment with CS at 2 mg/kg/d methylprednisolone equivalent dose, - Patients treated with 1 mg/kg/d of CS because the physician deemed they would not tolerate 2 mg/kg/d and who correspond to the definition of SR patients, - Patients who previously began CS therapy at a lower dose (at least 1 mg/kg/d methylprednisolone equivalent) for skin or upper GI GvHD but develop new GvHD in another organ system, - Patients who cannot tolerate corticosteroid tapering, i.e., begin of CS at 2.0 mg/kg/d, demonstrate response, but show disease progress before a 50% decrease from the initial starting dose of CS is achieved. Resistance to ruxolitinib is defined as any of the following (Mohty et al. 2020): - Progression of GvHD compared to baseline after at least 5 days of treatment with ruxolitinib, based either on objective increase in stage/grade, or new organ involvement; - Lack of improvement in GvHD (partial response or better) compared to baseline after at least 14 days of treatment with ruxolitinib; - Loss of response, defined as objective worsening of GvHD determined by increase in stage, grade or new organ involvement at any time after initial improvement - Absence of complete response or very good partial response at day 28 after ruxolitinib Intolerance to ruxolitinib is defined as: - GvHD manifestations that persist without improvement in patients who had grade 3 or higher treatment-emergent and ruxolitinib-attributed adverse event that did not resolve within 7 days of discontinuing ruxolitinib.
5. Signature of informed and written consent by the subject or by the subject’s legally acceptable representative for patients under guardianship or trusteeship.

Exclusion criteria 19

1. Patients with known hypersensitivity to vancomycin or to any of the excipients listed in the corresponding SmPC
2. Patients with active CMV colitis
3. Patients who had previously received other lines of systemic aGvHD treatment other than CS and ruxolitinib.
4. Grade II-IV hyper-acute GvHD as defined by the MD Anderson’s criteria (Saliba et al. 2007) (aGvHD onset within 14 days after allo-HSCT)
5. Overlap chronic GvHD as defined by the NIH Consensus Criteria (Jagasia et al. 2015)
6. Relapsed/persistent malignancy requiring rapid immune suppression withdrawal
7. Active uncontrolled infection according to the attending physician
8. Severe organ dysfunction unrelated to underlying GvHD, including: - Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction, with the exception of Gilbert syndrome). - Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months before Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support that requires therapy. - Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
9. Current or past (< 6 months) veno-occlusive disease or other uncontrolled complication unless otherwise agreed in writing by the sponsor.
10. Absolute neutrophil count <500/μL, confirmed within 3 days prior to pre-treatment start. Use of growth factor supplementation is allowed.
11. Absolute platelet count < 10 000/μL, confirmed within 3 days prior to pre-treatment start. Use of platelet infusion is allowed.
12. Patient with negative IgG EBV serology.
13. Current or past (< 6 months) evidence of toxic megacolon, bowel obstruction or gastrointestinal perforation.
14. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
15. Known allergy or intolerance to trehalose or maltodextrin.
16. Vulnerable patients such as: minors, persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention.
17. Females of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
18. Breastfeeding females. Females of childbearing potential should be willing to use an acceptable method of birth control such as hormonal contraception (progestogen-only may be sufficient), male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide for the course of the study. A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable. Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
19. Other ongoing interventional protocol that might interfere with the current study’s primary endpoint.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the efficacy of MaaT013 assessed by the overall response rate (ORR) of gastrointestinal (GI) acute grfat-versus-host disease (aGVHD) response at day 28 (D28).

Secondary endpoints 12

1. To evaluate MaaT013 safety
2. To evalutae ORR for GI at D56 and M3
3. To evaluate ORR for all organs at D28, D56 and M3
4. To evaluate the best ORR (for GI and all organs) acheived between D0 and D28
5. To assess duration of response
6. To assess overall survival (OS)
7. To assess progression-free survival (PFS)
8. To assess time to progression
9. To assess steroid-free survival
10. To evaluate the frequency of patients that tapered off CS
11. To measure the incidence of chronic GvHD
12. To evaluate changes in patient reported outcomes (PROs)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

MaaT PHARMA

Sponsor organisation

MaaT PHARMA

Address

70 Avenue Tony Garnier

City

Lyon

Postcode

69007

Country

France

Scientific contact point

Organisation

MaaT PHARMA

Contact name

Maat-Pharma Contact Point

Public contact point

Organisation

MaaT PHARMA

Contact name

Maat-Pharma Contact Point

Third parties 10

Locations

6 EU/EEA countries · 50 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 11 files

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

Application history

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