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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:
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patient population | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood and stool sample collection | Procedure | Collection of blood samples (55 mL) Collection of fecal samples (10g) |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Juliette JOUVE | Contact | +33 4 28 29 14 00 | orion@maat-pharma.com |
| Name | Affiliation | Role |
|---|---|---|
| Sarah Guenounou, MD | IUCT ONCOPOLE | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chu Amiens Picardie Site Sud | Recruiting | Amiens | 80054 | France |
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Prospective interventional with low risks and constraints study (RIPH2)
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| 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 |
| Chu de Caen | Recruiting | Caen | 14033 | France |
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| Chu Grenoble | Recruiting | Grenoble | 38043 | France |
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| Chu de Nice - L'Archet 1 | Recruiting | Nice | 06200 | France |
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| Aphp - Hopital Saint Antoine | Recruiting | Paris | 75012 | France |
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| Chu Lyon Sud | Active, not recruiting | Pierre-Bénite | 69310 | France |
| Chu La Miletrie | Recruiting | Poitiers | 86021 | France |
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| Chu de Rennes - Hopital Pontchaillou | Active, not recruiting | Rennes | 35033 | France |
| Institut Universitaire Du Cancer de Toulouse - Oncopole | Recruiting | Toulouse | 31059 | France |
|
| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
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