Prospective Interventional Study Exploring the Microbiota Recolonization in SR-GvHD Patients Receiving MaaT013 (ORION)

PrOspective inteRventional Study Exploring the mIcrobiota recolONization in Steroid-Refractory Graft-versus-Host Disease Patients Receiving MaaT013

The objective of the ORION study is to explore the changes of gut microbiota composition following MaaT013 administration and its impact on the immune system in GVHD patients.

Study Overview

• Status: Recruiting
• Conditions: Steroid Refractory GVHD; Intestinal GVHD
• Intervention / Treatment: Procedure: Blood and stool sample collection

Detailed Description

The french regulatory authority ANSM approved in July 2019 the use of MaaT013, a pooled microbiome-based enema formulation, under a formalized named-patient use program in France called "Autorisation Temporaire d'Utilisation - ATU nominative protocolisée - ATUn" or Early Access.

The ATUn is indicated to provide a benefit in the treatment of patients with grade III-IV aGVHD:

• In case of initial resistance to CS alone or in association or in case of failure to other treaments
• In first-line therapy in association with CS in case of steroid-dependance (inability to taper CS dose <0.5 mg/kg/d)
• In case of digestive aGvHD with overlap syndrome The objective of the ORION study is to explore the changes of gut microbiota composition following MaaT013 administration and its impact on the immune system in GVHD patients.

Blood and stool samples will be collected at each visit which explained why the study is thus categorized as research involving the human person with low risks and constraints clinical trial (RIPH2).

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Juliette JOUVE; Phone Number: +33 4 28 29 14 00; Email: orion@maat-pharma.com

Study Locations

• France
  • Amiens, France, 80054
    • Recruiting
    • CHU Amiens Picardie site Sud
    • Principal Investigator: AMANDINE CHARBONNIER, MD
    • Contact: AMANDINE CHARBONNIER, MD; Phone Number: 03 22 45 59 14; Email: charbonnier.amandine@chu-amiens.fr
  • Caen, France, 14033
    • Recruiting
    • CHU de Caen
    • Contact: CHANTEPIE SYLVAIN, MD; Phone Number: 02 31 27 20 73; Email: chantepie-s@chu-caen.fr
    • Principal Investigator: CHANTEPIE SYLVAIN, MD
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble
    • Contact: CARRE MARTIN, MD; Phone Number: 04 76 76 57 55; Email: MCarre1@chu-grenoble.fr
    • Principal Investigator: CARRE MARTIN, MD
  • Nice, France, 06200
    • Recruiting
    • CHU de Nice - l'Archet 1
    • Contact: LOSCHI MICHAEL, MD; Phone Number: 04 92 03 58 41; Email: loschi.m@chu-nice.fr
    • Principal Investigator: LOSCHI MICHAEL, MD
  • Paris, France, 75012
    • Recruiting
    • APHP - Hopital Saint Antoine
    • Principal Investigator: FLORENT MALARD
    • Contact: FLORENT MALARD, MD; Phone Number: 01 49 28 34 39; Email: florent.malard@aphp.fr
  • Pierre-Bénite, France, 69310
    • Active, not recruiting
    • CHU Lyon Sud
  • Poitiers, France, 86021
    • Recruiting
    • CHU La Milétrie
    • Contact: DESMIER DEBORAH, MD; Phone Number: 05 49 44 44 44; Email: deborah.desmier@chu-poitiers.fr
  • Rennes, France, 35033
    • Active, not recruiting
    • CHU de Rennes - Hôpital Pontchaillou
  • Toulouse, France, 31059
    • Recruiting
    • Institut Universitaire du Cancer de Toulouse - Oncopole
    • Contact: SARAH GUENOUNOU, MD; Phone Number: 05 31 15 63 92; Email: guenounou.sarah@iuct-oncopole.fr
    • Principal Investigator: SARAH GUENOUNOU, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient ≥18 years old with Grade III-IV aGVHD with gut involvement undergoing treatment with MaaT013 through named-patient use program ATUn / Early Access
• Signature of informed and written consent by the subject or by the subject's legally acceptable representative for patients under guardianship or trusteeship.
• Affiliated or recipient from a social security scheme

Exclusion Criteria:

• Pregnancy and breastfeeding
• Vulnerable patients such as: minors, persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patient population; The population of the study will be adult patients with GI-aGVHD grade III to IV undergoing MaaT013 treatment through named-patient use program ATUn (Early Access Program). Blood and stool samples will be collected at each visit to analyse the gut microbiota and the immune cells.	Procedure: Blood and stool sample collection; Collection of blood samples (55 mL) Collection of fecal samples (10g)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of gut microbiota diversity	Diversity of gut microbiota will be evaluated using alpha-diversity metric (Simpson or Shannon or Richness indice) throughout the study	inclusion (day 0) to month 6
Change of gut microbiota composition	Sample comparisons will be performed using similarity metric such as Bray-Curtis, Jaccard distances, Sorensen, Pearson or Spearman indice.	inclusion (day 0) to month 6
Change of gut microbiota composition (phylogenetic profiles)	Gut microbiota composition will be evaluated with phylogenetic profiling. Relative abundance of bacterial taxa will be described at each visit throughout the study.	inclusion (day 0) to month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between gut microbiota and immune parameters	Multiparameter analyses will be performed to identify correlations between changes in gut microbiota composition and immune parameters (Citrulline, Zonulin, ST2, 3 indoxyl sulfate, Reg3a, Total antioxidant status, TGFb1.2.3., IL-1b, IL-2, sIL-2ra, IL-6, IL-8, IL10, IL17-A, IL-18, IFNg, TNFa, sCD14, MCP1, CCL25, CCL28, sCD30, CXCL10)	inclusion (day 0) to month 6
Gut microbiota baseline characterization based on clinical response	Stratification of patients will be based on response to MaaT013 treatment at day 28. Then gut microbiota composition will be described in responder versus non responder patients.	day 0
Change in immune parameters following MaaT013 administration	Cytokines and immune parameters of interest (Citrulline, Zonulin, ST2, 3 indoxyl sulfate, Reg3a, Total antioxidant status,TGFb1.2.3., IL-1b, IL-2, sIL-2ra, IL-6, IL-8, IL10, IL17-A, IL-18, IFNg, TNFa, sCD14, MCP1, CCL25, CCL28, sCD30, CXCL10) will be measured in plasma/serum by Luminex and ELISA at each visit and compared to baseline. Results will be expressed as ratios on D0 value and heatmap. Peripheral blood mononuclear cells will be purified then analyzed by flow cytometry using specific antibodies (CD4, CD8α, CD8β,TCRαβ, CD49a, CCR6, CXCR6, CD25, CD127, CCR7, CD69, CD45RA, CD27, CD57, GITR, CD39, C. Transcriptomic analysis by single cell CITE-seq will be performed on some lymphocytes subgroups.	inclusion (day 0) to month 6

Collaborators and Investigators

• Sponsor: MaaT Pharma
• Investigators: Principal Investigator: Sarah Guenounou, MD, IUCT Oncopole

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 24, 2021

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: gut microbiota; fecal microbiotherapy; intestinal GvHD
• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: MPOH07

Drug and device information, study documents

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