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

Amyotrophic Lateral Sclerosis Clinical Trial

— IASO  

Official title:

Safety, Tolerability and Gut microbIota AnalysiS of an Oral Microbiotherapy in Amyotrophic Lateral Sclerosis; an Open-label Phase 1b Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05889572
• Other study ID #: MPNS01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: June 8, 2023
• Est. completion date: December 2024

Study information

• Verified date: June 2024
• Source: MaaT Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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 (?FS/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

Related Conditions & MeSH terms

• ALS
• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• MaaT033
MaaT033 is a Microbiome Ecosystem Therapy (MET), composed of allogeneic, full-ecosystem pooled biotherapeutic gut microbiota.

Locations

Country	Name	City	State
France	Centre Hospitalier Universitaire de Lille - CIC	Lille
France	Hôpital de la Pitié-Salpêtrière - CIC Neuroscience	Paris

Sponsors (1)

Lead Sponsor	Collaborator
MaaT Pharma

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Day 84
Secondary	Changes in gut microbiota profile	Analysis of fecal samples to assess gut microbiota alpha- and beta-diversity indices	From Day -5 to Day 84 (at Day -5, Day 10, Day 28, Day 56 and Day 84)
Secondary	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.	From Day -5 to Day 84
Secondary	Changes in levels of fecal calprotectin	Changes from baseline (Day -5) of fecal calprotectin at Day 10, Day 28, Day 56 and Day 84	From Day -5 to Day 84