A multi-center randomized, double blinded phase IIb trial evaluating oral pooled fecal microbiotherapy MaaT033 to prevent allogeneic hematopoietic cell transplantation complications

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] - Hemic and Lymphatic Diseases [C15]

Trial duration

13 Sep 2023 → ongoing

Decision date (initial)

2024-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

MaaT Pharma

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Prophylaxis, Therapy

To compare the efficacy of MaaT033 with its placebo on overall survival at 12 months after alloHCT

Secondary objectives 13

1. To evaluate GvHD-free survival at M12 after alloHCT.
2. To evaluate GvHD-free relapse-free (GRFS) survival at M12 after alloHCT.
3. To evaluate OS and Relapse-free survival (RFS) at M24 after alloHCT
4. To evaluate MaaT033 efficacy in dysbiosis correction through the evolution of microbiota composition with alpha- and beta-diversity indexes
5. To evaluate the cumulative incidence of grade 2-4 and grade 3-4 severe acute GvHD at M6 after alloHCT.
6. To evaluate the cumulative incidence of cGvHD as assessed by NIH Consensus Criteria at M6, M12 and M24 after alloHCT.
7. To evaluate the cumulative incidence of NRM, infectious-related mortality and GvHD-related mortality at M6, M12 and M24 after alloHCT.
8. To evaluate the proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3 within 12 months after alloHCT.
9. To evaluate the proportion of subjects who have discontinued immune suppression therapies including standard of care GvHD prophylaxis and steroid treatment at M6 and M12 after alloHCT.
10. To evaluate the neutrophil recovery rate at D30 and the time to neutrophil recovery.
11. To evaluate the platelet recovery rate at D30 and the time to platelet recovery.
12. To evaluate the quality of life (QoL) within 12 months after alloHCT.
13. To evaluate the nutritional status of the subjects.

Conditions and MedDRA coding

Patients with hematologic malignancies and undergoing allogenic hematopoietic cell transplantation

Study design 1 period

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 7

1. Age ≥ 50 years old.
2. Presence of a hematologic malignancy for which an alloHCT is indicated with a reduced toxicity or reduced intensity conditioning regimen. Note: - Reduced toxicity or reduced intensity conditioning regimen is defined as any conditioning regimen that does not fit the definitions provided in the exclusion criteria. - Subjects planned to receive sequential protocols combining salvage chemotherapy with reduced intensity conditioning (RIC) and alloHCT can be included in the trial.
3. Polynuclear neutrophils > 0.5 G/L.
4. Received wide spectrum antibiotics within the last 90 days prior to inclusion. Note: Use of wide spectrum antibiotic is defined as use of at least 3 days of antibiotics within the last 90 days prior to inclusion, which is defined as randomization. For the list of wide spectrum antibiotics, refer to section 5.1 of Protocol.
5. Karnofsky index ≥ 70%.
6. Availability of a sibling donor, an unrelated stem-cell donor or a familial haploidentical donor.
7. Signature of informed and written consent by the subject or by the subject’s legally acceptable representative for subjects under guardianship or trusteeship.

Exclusion criteria 22

1. Planned to receive a non-myeloablative conditioning regimen (2 Gray total body irradiation (TBI) +/- purine analog, fludarabine + cyclophosphamide or equivalent).
2. Planned to receive a conventional myeloablative conditioning regimen (e.g. high dose cyclophosphamide and high dose TBI (≥10Gy); high dose busulfan (12.8 mg/kg IV) + high dose cyclophosphamide).
3. Receiving a manipulated graft (in-vitro T-cell depletion).
4. Planned to receive a conditioning regimen with alemtuzumab (CAMPATH®).
5. Planned to receive alloHCT with cord blood cells.
6. Planned to receive alloHCT from unrelated donor with ≥ 3/10 HLA-mismatches.
7. Receiving a large spectrum antibiotic at time of randomization.
8. Planned to receive vedolizumab or abatacept for GvHD prophylaxis.
9. Documented creatinine clearance <30 mL/min.
10. Documented bilirubin or amino-transferases abnormalities contra-indicating alloHCT. Note: Bilirubin > 3 x Upper normal limits (ULN), or Aspartate Transaminase / Alanine Transaminase (AST/ALT) > 5 x ULN to be considered as an exclusion criterion.
11. Documented cardiac ejection fraction less than 40%. Note: The most recent cardiac ejection fraction measured in the previous 6 months prior screening documenting values below 40%.
12. Documented pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO). Note: The most recent DLCO measured in the previous 6 months prior screening documenting values below 50%.
13. Pregnancy and breastfeeding (urine or serum pregnancy test within 72 hours prior to randomization). Subjects (males and 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 (up to M12). A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable. A female is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 Months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 Months of amenorrhea, a single FSH measurement is insufficient.
14. Documented confirmed or suspected intestinal ischemia.
15. Documented confirmed or suspected toxic megacolon, bowel obstruction or gastrointestinal (GI) perforation.
16. Any documented history of GI surgery in the past 3 months.
17. Any documented history of chronic digestive disease (Crohn’s disease, ulcerative colitis (UC), inflammatory bowel disease or other relevant digestive condition according to physician’s judgement).
18. Known allergy or intolerance to trehalose or maltodextrin.
19. Negative EBV-IgG serology.
20. 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.
21. Vulnerable subjects such as: persons deprived of liberty, persons in Intensive Care Unit (ICU) unable to provide ICF prior to the intervention, persons under legal protection according to the national law.
22. Other ongoing interventional protocol that might interfere with the current study’s primary endpoint. Note: Subjects previously included in interventional trials and no longer receiving the previous study medication but in follow-up, can participate in the PHOEBUS trial with a wash-out period of 5 half-lives of previous study medication as long as they meet all respective inclusion and none of the exclusion criteria.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Parameter: Overall survival (OS). For this endpoint, OS is defined as the time from the date of alloHCT to the date of death from any cause.

Secondary endpoints 1

1. See table 1 of the protocol for details

Investigational products

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

Test 1

Placebo 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

Head of Clinical Development Department

Public contact point

Organisation

Maat Pharma

Contact name

Human Resources Manager

Third parties 2

Locations

5 EU/EEA countries · 56 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

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Documents 41 files

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

Application history

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