Safety and Tolerability Evaluation of MaaT033 (CIMON)

Safety Phase I Evaluation of MaaT033, a Lyophilized Full-ecosystem Gut Microbiota Delayed-release Capsule, In HeMatOlogy Malignant Patients Under iNtensive Chemotherapy (CIMON)

Richness and diversity of gut microbiota are increasingly found to be associated with cancer outcomes. Moreover, an adequately responsive immune system seems to rely on the existence of a functioning gut ecosystem that includes the microbiota and its natural environment.

Cancer by itself, but also cancer treatments - in particular chemotherapy - induce gut dysbiosis, impair the constant reparation mechanisms of the gut epithelium, disrupt immune homeostasis, and stunt immune responsiveness.

The objective of MaaT033 is to (1) prevent the decay of the gut ecosystem (dysbiosis) to preserve immune homeostasis, (2) restore and optimize the gut ecosystem to full functionality including its role in repairing the gut epithelium and healthy gut barrier, and (3) maintain a restored gut ecosystem and fully functional immune homeostasis.

Restoring the full gut ecosystem and its associated microbiota could become an important therapeutic option to improve clinical outcomes and control adverse events of conventional approaches, including immunotherapy in cancer patients.

As a first step, MaaT033 capsules containing lyophilized, pooled, full-ecosystem microbiota in its natural environment are to be tested for their safety and tolerability in hematological malignant patients, who are exposed to intensive rounds of chemotherapy and antibiotics.

Study Overview

• Status: Completed
• Conditions: Hematologic Diseases; Chemotherapy Effect
• Intervention / Treatment: Drug: MaaT033 capsule

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Angers, France
    • CHU Angers
  • Nice, France
    • CHU Nice
  • Paris, France
    • APHP St Antoine
  • Toulouse, France
    • IUCT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female
2. Age ≥ 18 years
3. Patients diagnosed with AML defined according to WHO 2016 criteria with ≥20% leukemic blasts in the bone marrow or with high- risk myelodysplastic syndrome, receiving intensive chemotherapy
4. Patients healthy enough to likely receive their consolidation or second cycle of chemotherapy after induction chemotherapy
5. Patients healthy enough to likely receive HSCT
6. Informed written consent
7. Patient recovered from neutropenia

Exclusion Criteria:

1. Acute promyelocytic leukemia (AML-M3)
2. AML secondary to myeloproliferative disorder or chronic myelomonocytic leukemia (CMML)
3. Acute myeloid leukemia BCR-ABL1+
4. Active CNS leukemia
5. Patients with a life expectancy of <70 days according to investigator's opinion, or subject to therapeutic limitations
6. Confirmed or suspected intestinal ischemia
7. Confirmed or suspected toxic megacolon or gastrointestinal perforation
8. Active uncontrolled infection according to the attending physician
9. Any gastro-intestinal bleeding in the past 3 months
10. Any history of gastro-intestinal surgery in the past 3 months
11. Any history of inflammatory bowel disease
12. Any counter-indication to swallow capsules
13. Enrollment in another trial that may interfere with this study
14. Known allergy or intolerance to trehalose, maltodextrin or PEG
15. Women of childbearing potential without efficient contraceptive protection
16. Pregnant or breastfeeding
17. Patients with EBV-negative serology
18. Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development;
19. Exclusion period of a previous study
20. Administrative or legal supervision
21. Confirmed positive result to SARS-CoV-2 nasopharyngeal test at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MaaT033 treatment; A Lyophilized Full-ecosystem Gut Microbiota Delayed-release Capsule	Drug: MaaT033 capsule; Oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of MaaT033-related, treatment-emergent (serious) adverse events, grade >3, as assessed by CTCAE v4.0	Evaluation of safety and tolerability of MaaT033 in patients with hematologic malignancies	From treatment start (V1, end of aplasia) to the end of the study (end of consolidation or up to 10 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose regimen evaluation	Activity assessment of the different dose regimens defined as bacterial "engraftment" of the product	From treatment start (V1, end of aplasia) to the end of the study (end of consolidation or up to 10 weeks)

Collaborators and Investigators

• Sponsor: MaaT Pharma
• Investigators: Principal Investigator: Christian Recher, Pr, IUCT

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): December 13, 2021
• Study Completion (Actual): December 13, 2021

Study Registration Dates

• First Submitted: October 25, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: microbiota; microbiotherapy
• Additional Relevant MeSH Terms: Hematologic Diseases
• Other Study ID Numbers: MPOH05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No