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Safety and Gut Microbiota Analysis of an Oral Microbiotherapy in Patients With Amyotrophic Lateral Sclerosis (IASO)

Primary Purpose

Amyotrophic Lateral Sclerosis, ALS

Status
Recruiting
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
MaaT033
Sponsored by
MaaT Pharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Microbiotherapy, Amyotrophic Lateral Sclerosis, Neurodegenerative disease, ALS

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female subjects aged between18 and 80 years ALS meeting the revised El Escorial criteria for possible, probable, laboratory-supported probable, or definite ALS (familial or sporadic) Time since first motor deficit at screening: at least 6 months, up to 24 months Slope of progression of ALS Functional Rating Scale - revised (ALSFRS-R) from date of symptom onset to date of screening test (ΔFS/number of months) between [0.4 and 1.1] Able to swallow study treatments (including capsules without opening or chewing them) as per the investigator's assessment SVC (Slow Vital Capacity) equal to or greater than 70% of the predicted normal value for sex, height, and age at the screening visit If taking riluzole, subject must be on a stable dose for ≥30 days Signature of written informed consent by subject Exclusion Criteria: Subjects with a non-invasive ventilation, a tracheotomy and /or a gastrostomy Known autoimmune diseases, inflammatory disorders (SLE, Rheumatoid arthritis, connective tissue disorder) or chronic infections (HIV, hepatitis B, or C infection, Tuberculosis) Known hypersensitivity to rifaximin or macrogol or any of its components Known allergy or intolerance to trehalose, maltodextrin or Polyethylene Glycol (PEG) Documented hepatic impairment (Alanine Transaminase/ Aspartate Transaminase > 5N) Subject with white blood cells < 4000/ mm3; Polynuclear neutrophils < 1.5 G/ L Active infection requiring systemic antimicrobial therapy within 2-week prior to screening visit Active infection requiring systemic antimicrobial therapy between screening and baseline Medical condition requiring proton pump inhibitors (PPIs) Gastrointestinal obstruction or perforation Any gastro-intestinal bleeding in the past 3 months Gastric emptying disorders (gastroparesis) Toxic megacolon Severe forms of inflammation of the intestinal tract, including Crohn's disease and ulcerative colitis Severe vital organ dysfunctions unrelated to ALS and not compatible with experimental treatment, as per the investigator's assessment Subjects with negative IgG serology for Epstein Barr virus (EBV) Women of childbearing potential1 without effective contraceptive protection Nursing or pregnant women Any condition that, in the opinion of the investigator, may interfere with full participation in the study, including administration of study drug (and its preparation procedure) and attendance at required study visits; represent a significant risk to the subject; or interfere with the interpretation of study data Enrollment in another trial or expanded access program that may interfere with this study Guardianship/legal protection/curatorship of subjects Vulnerable subjects such as: persons deprived of liberty, persons in intensive care units unable to provide informed consent prior to the procedure

Sites / Locations

  • Centre Hospitalier Universitaire de Lille - CICRecruiting
  • Hôpital de la Pitié-Salpêtrière - CIC NeuroscienceRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

MaaT033

Arm Description

Route of administration: oral (capsule) Between D-5 to D-1: Bowel preparation with Macrogol and Rifamixin Between D1 to D28: MaaT033 treatment period 1 Between D28 to D56: MaaT033 treatment period 2

Outcomes

Primary Outcome Measures

Safety and tolerability: Incidence of Treatment Emergent Adverse Events (TEAE) grade >3, according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
To assess the safety and tolerability of MaaT033 treatment

Secondary Outcome Measures

Changes in gut microbiota profile
Analysis of fecal samples to assess gut microbiota alpha- and beta-diversity indices
Changes in levels of biomarkers in blood
Changes from baseline (Day -5) of neutrophil/ lymphocyte ratio, Interleukins (IL): IL-2, IL-6 and IL-8, Interferon gamma (IFNg), Tumor Necrosis Factor alpha (TNFa), Monocyte Chemoattractant Protein-1 (MCP-1), Transforming Growth Factor-beta (TGFb), the soluble subtype of CD14 (sCD14), C-reactive protein (CRP), erythrocyte sedimentation rate, plasma soluble Lipopolysaccharide Binding Protein (LBP), creatinin and serum Short-Chain Fatty Acids (SCFA) at Day 28, Day 56 and Day 84. Changes from baseline (Day -5) of serum Neurofilament light (NfL) at Day 56 and Day 84.
Changes in levels of fecal calprotectin
Changes from baseline (Day -5) of fecal calprotectin at Day 10, Day 28, Day 56 and Day 84

Full Information

First Posted
April 17, 2023
Last Updated
October 10, 2023
Sponsor
MaaT Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT05889572
Brief Title
Safety and Gut Microbiota Analysis of an Oral Microbiotherapy in Patients With Amyotrophic Lateral Sclerosis
Acronym
IASO
Official Title
Safety, Tolerability and Gut microbIota AnalysiS of an Oral Microbiotherapy in Amyotrophic Lateral Sclerosis; an Open-label Phase 1b Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2023 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MaaT Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this pilot study is to assess the safety and tolerability of multiple doses of MaaT033 in ALS patients and to analyze the gut microbiota composition and evolution before considering a larger randomized controlled efficacy study.
Detailed Description
This is a prospective, single arm, open-label study. The target population includes subjects with a recent disease onset defined as the time from first motor deficit at screening of at least 6 months and up to 24 months and removing very rapid/slow progressors based on the ALS Functional Rating Scale - Revised (ALSFRS-R) progression slope. After a screening period (clinical examination, blood sampling), subject will come for a baseline visit (clinical examination, blood and feces sampling) and to initiate a bowel preparation phase. Five days later, subject will come back to the study site (clinical examination, blood sampling) to initiate a first Maat033 treatment period of 28-day. Ten days after MaaT033 treatment initiation a remote visit is included (feces sampling) to check the subject safety/tolerability. After the first Maat033 treatment period, subject will come to the study site (clinical examination, blood and feces sampling) to initiate the second MaaT033 treatment period of 28-day. At the end of the second Maat033 treatment period subjects will come to the study site (clinical examination, blood and feces sampling) and start a 28-day follow-up period without treatment. Study completion is defined when all subjects enrolled completed the study follow-up period (clinical examination, blood and feces sampling) or earlier if a subject discontinued the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis, ALS
Keywords
Microbiotherapy, Amyotrophic Lateral Sclerosis, Neurodegenerative disease, ALS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MaaT033
Arm Type
Experimental
Arm Description
Route of administration: oral (capsule) Between D-5 to D-1: Bowel preparation with Macrogol and Rifamixin Between D1 to D28: MaaT033 treatment period 1 Between D28 to D56: MaaT033 treatment period 2
Intervention Type
Drug
Intervention Name(s)
MaaT033
Intervention Description
MaaT033 is a Microbiome Ecosystem Therapy (MET), composed of allogeneic, full-ecosystem pooled biotherapeutic gut microbiota.
Primary Outcome Measure Information:
Title
Safety and tolerability: Incidence of Treatment Emergent Adverse Events (TEAE) grade >3, according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Description
To assess the safety and tolerability of MaaT033 treatment
Time Frame
Day 84
Secondary Outcome Measure Information:
Title
Changes in gut microbiota profile
Description
Analysis of fecal samples to assess gut microbiota alpha- and beta-diversity indices
Time Frame
From Day -5 to Day 84 (at Day -5, Day 10, Day 28, Day 56 and Day 84)
Title
Changes in levels of biomarkers in blood
Description
Changes from baseline (Day -5) of neutrophil/ lymphocyte ratio, Interleukins (IL): IL-2, IL-6 and IL-8, Interferon gamma (IFNg), Tumor Necrosis Factor alpha (TNFa), Monocyte Chemoattractant Protein-1 (MCP-1), Transforming Growth Factor-beta (TGFb), the soluble subtype of CD14 (sCD14), C-reactive protein (CRP), erythrocyte sedimentation rate, plasma soluble Lipopolysaccharide Binding Protein (LBP), creatinin and serum Short-Chain Fatty Acids (SCFA) at Day 28, Day 56 and Day 84. Changes from baseline (Day -5) of serum Neurofilament light (NfL) at Day 56 and Day 84.
Time Frame
From Day -5 to Day 84
Title
Changes in levels of fecal calprotectin
Description
Changes from baseline (Day -5) of fecal calprotectin at Day 10, Day 28, Day 56 and Day 84
Time Frame
From Day -5 to Day 84

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects aged between18 and 80 years ALS meeting the revised El Escorial criteria for possible, probable, laboratory-supported probable, or definite ALS (familial or sporadic) Time since first motor deficit at screening: at least 6 months, up to 24 months Slope of progression of ALS Functional Rating Scale - revised (ALSFRS-R) from date of symptom onset to date of screening test (ΔFS/number of months) between [0.4 and 1.1] Able to swallow study treatments (including capsules without opening or chewing them) as per the investigator's assessment SVC (Slow Vital Capacity) equal to or greater than 70% of the predicted normal value for sex, height, and age at the screening visit If taking riluzole, subject must be on a stable dose for ≥30 days Signature of written informed consent by subject Exclusion Criteria: Subjects with a non-invasive ventilation, a tracheotomy and /or a gastrostomy Known autoimmune diseases, inflammatory disorders (SLE, Rheumatoid arthritis, connective tissue disorder) or chronic infections (HIV, hepatitis B, or C infection, Tuberculosis) Known hypersensitivity to rifaximin or macrogol or any of its components Known allergy or intolerance to trehalose, maltodextrin or Polyethylene Glycol (PEG) Documented hepatic impairment (Alanine Transaminase/ Aspartate Transaminase > 5N) Subject with white blood cells < 4000/ mm3; Polynuclear neutrophils < 1.5 G/ L Active infection requiring systemic antimicrobial therapy within 2-week prior to screening visit Active infection requiring systemic antimicrobial therapy between screening and baseline Medical condition requiring proton pump inhibitors (PPIs) Gastrointestinal obstruction or perforation Any gastro-intestinal bleeding in the past 3 months Gastric emptying disorders (gastroparesis) Toxic megacolon Severe forms of inflammation of the intestinal tract, including Crohn's disease and ulcerative colitis Severe vital organ dysfunctions unrelated to ALS and not compatible with experimental treatment, as per the investigator's assessment Subjects with negative IgG serology for Epstein Barr virus (EBV) Women of childbearing potential1 without effective contraceptive protection Nursing or pregnant women Any condition that, in the opinion of the investigator, may interfere with full participation in the study, including administration of study drug (and its preparation procedure) and attendance at required study visits; represent a significant risk to the subject; or interfere with the interpretation of study data Enrollment in another trial or expanded access program that may interfere with this study Guardianship/legal protection/curatorship of subjects Vulnerable subjects such as: persons deprived of liberty, persons in intensive care units unable to provide informed consent prior to the procedure
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Juliette Jouve
Phone
+33 4 28 29 14 00
Email
contact@maat-pharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gaelle Bruneteau, MD, PhD
Organizational Affiliation
Hôpital de la Pitié-Salpêtrière - CIC Neuroscience
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Hospitalier Universitaire de Lille - CIC
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Véronique DANEL, MD
Facility Name
Hôpital de la Pitié-Salpêtrière - CIC Neuroscience
City
Paris
ZIP/Postal Code
75013
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaelle Bruneteau, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Gut Microbiota Analysis of an Oral Microbiotherapy in Patients With Amyotrophic Lateral Sclerosis

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