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

Steroid Refractory GVHD Clinical Trial

— ORION  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05017688
• Other study ID #: MPOH07
• Status: Recruiting
• Phase: N/A
• Start date: October 6, 2021
• Est. completion date: December 2024

Study information

• Verified date: October 2023
• Source: MaaT Pharma
• Contact: Juliette JOUVE
• Phone: +33 4 28 29 14 00
• Email: orion[@]maat-pharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: December 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Graft vs Host Disease
• Intestinal GVHD
• Steroid Refractory GVHD

Intervention

Procedure:
• Blood and stool sample collection
Collection of blood samples (55 mL) Collection of fecal samples (10g)

Locations

Country	Name	City	State
France	Chu Amiens Picardie Site Sud	Amiens
France	Chu de Caen	Caen
France	Chu Grenoble	Grenoble
France	Chu de Nice - L'Archet 1	Nice
France	Aphp - Hopital Saint Antoine	Paris
France	Chu Lyon Sud	Pierre-Bénite
France	Chu La Miletrie	Poitiers
France	Chu de Rennes - Hopital Pontchaillou	Rennes
France	Institut Universitaire Du Cancer de Toulouse - Oncopole	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
MaaT Pharma

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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, CD8a, CD8ß,TCRaß, 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