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

MaaT Pharma40 enrolled

Overview

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.

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

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Intestinal GVHD Steroid Refractory GVHD

Interventions

Blood and stool sample collectionPROCEDURE

Collection of blood samples (55 mL) Collection of fecal samples (10g)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 85 Years

Medical Language ↔ Plain English

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.

Locations (9)

Chu Amiens Picardie Site Sud

Amiens, France

RECRUITING

Chu de Caen

Caen, France

RECRUITING

Chu Grenoble

Grenoble, France

Outcomes

Primary Outcomes

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

Time frame: 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.

Time frame: 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.

Time frame: inclusion (day 0) to month 6

Secondary Outcomes

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)

Time frame: 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.

Time frame: 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.

Central Contacts

Juliette JOUVE

CONTACT

+33 4 28 29 14 00 orion@maat-pharma.com

Data from ClinicalTrials.gov

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