MaaT013 As Salvage Therapy in Ruxolitinib Refractory GI-aGVHD Patients

NCT04769895 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: MPOH06
• Study Type: interventional
• Target: 66
• Locations: 6 countries
• Sites: 50

Brief Summary

MaaT013 showed interesting results in steroids and ruxolitinib-resistant aGVHD patients with gut involvement (55% ORR at D28) and 47% and 39% OS at 6 and 12 months respectively (Malard 2020), therefore warrant being tested as salvage therapy in steroid and JAK inhibitors-resistant GI-aGvHD patients. Given the absence of an approved 3rd line strategy or 2nd line strategy in ruxolitinib intolerant patients and the extremely poor prognosis of these patients, who are mostly left with no viable therapeutic option, a single-arm open-label design was proposed.

Conditions

Acute Graft Versus Host Disease in Intestine; Steroid Refractory GVHD

Keywords

Microbiotherapy; Fecal microbiota transfer; Gastro intestinal acute GVHD; ruxolinib refractory

Outcome Measures

Primary Outcomes (1)

• ORR of gastro intestinal-aGvHD

  Overall Response Rate (Complete Response + Very Good Partial Response + Partial Response)

  Day 28

Secondary Outcomes (9)

• Safety and tolerability

  Day 28

• Safety and tolerability

  Month 3

• Safety and tolerability

  Month 12

• aGvHD ORR

  Day 28, Day 56 and Month 3

• GI aGvHD ORR

  Day 56 and Month 3

Other Outcomes (1)

• Exploratory endpoint

  Day 28

Study Arms (1)

MaaT013

EXPERIMENTAL

Route of administration: rectal (enema) Study drug dose: 4 enemas in total: Week 1: * D0-D1: vancomycin pre-treatment (250mg per os, 4 times a day for 2 days) * D2: 1 dose * Between D3 to D5: 1 dose Week 2: 1 dose (7 +/- 2 days after the last dose) Week 3: 1 dose (7 +/- 2 days after the last dose) A supplementary dose can be prescribed in case of GvHD relapse or massive antibiotic use during the study.

Drug: MaaT013

Interventions

MaaT013 DRUG

MaaT013 is made of allogeneic, full-ecosystem pooled biotherapeutic intestinal microbiota

MaaT013

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Allo-HSCT with any type of donor, stem cell source, GVHD prophylaxis or conditioning regimen.
• Acute GvHD episode with GI involvement per MAGIC guidelines (= grades II to IV), with or without involvement of other organs
• Patients resistant to steroids AND either resistant to OR with intolerance to ruxolitinib OR with contra-indication to ruxolitinib:

You may not qualify if:

• Patients with known hypersensitivity to vancomycin or to any of the excipients listed in the corresponding SmPC
• Patients with active CMV colitis
• Patients who had previously received other lines of systemic aGvHD treatment other than CS and ruxolitinib.
• Grade II-IV hyper-acute GvHD
• Overlap chronic GvHD
• Relapsed/persistent malignancy requiring rapid immune suppression withdrawal.
• Active uncontrolled infection according to the attending physician
• Severe organ dysfunction unrelated to underlying GvHD, including:
• Cholestatic disorders or unresolved veno-occlusive disease of the liver (defined as persistent bilirubin abnormalities not attributable to GvHD and ongoing organ dysfunction).
• Clinically significant or uncontrolled cardiac disease including unstable angina, acute myocardial infarction within 6 months before Day 1 of study drug administration, New York Heart Association Class III or IV congestive heart failure, circulatory collapse requiring vasopressor or inotropic support, or arrhythmia that requires therapy.
• Clinically significant respiratory disease that requires mechanical ventilation support or 50% oxygen.
• Current or past veno-occlusive disease or other uncontrolled complication unless otherwise agreed in writing by the sponsor.
• Absolute neutrophil count \<500/µL for 3 consecutive days. Use of growth factor supplementation is allowed.
• Absolute platelet count \< 10 000/µL. Use of platelet infusion is allowed.
• Patient with negative IgG EBV serology.

Sponsors & Collaborators

• MaaT Pharma: lead

Study Sites (50)

Medizinische Universität Innsbruck

Innsbruck, Austria

Location

Ordensklinikum Linz Elisabethinen

Linz, Austria

Location

Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan

Bruges, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, Belgium

Location

Centre Hospitalier Universitaire Amiens-Picardie - Site Sud

Amiens, France

Location

Centre Hosptitalier Universitaire d'Angers

Angers, France

Location

CHU de Caen

Caen, France

Location

Centre Hospitalier Universitaire Grenoble Alpes

Grenoble, France

Location

CHRU Lille - Hopital Claude Huriez

Lille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Hôpital Lapeyronie

Montpellier, France

Location

Hôpital l'Archet

Nice, France

Location

APHP St Antoine

Paris, France

Location

Hôpital Haut-Lévêque

Pessac, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, France

Location

Centre Hospitalier Universitaire de Poitiers

Poitiers, France

Location

Hôpital Pontchaillou

Rennes, France

Location

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, France

Location

Institut Universitaire du Cancer de Toulouse Oncopole

Toulouse, France

Location

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, France

Location

Helios Klinikum Berlin-Buch

Berlin, Germany

Location

Universitätsmedizin Mannheim

Mannheim, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Germany

Location

Universitätsklinik Ulm - Oberen Eselsberg

Ulm, Germany

Location

Universitatsklinikum Wurzburg

Würzburg, Germany

Location

Azienda Ospedaliera Regionale San Carlo

Ancona, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

Bologna, Italy

Location

Istituto di Ricovero e Cura a Carattere Scientifico - Ospedale Policlinico San Martino

Genova, Italy

Location

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Italy

Location

IRCCS Ospedale San Raffaele

Milan, Italy

Location

Grande Ospedale Metropolitano Bianchi Melacrino Morelli

Reggio Calabria, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Azienda Ospedaliero-Universitaria Citta della Salute e della Scienza di Torino

Torino, Italy

Location

Presidio Ospedaliero Universitario Santa Maria della Misericordia

Udine, Italy

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)

Barcelona, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

El Palmar, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Spain

Location

Clinica Universidad de Navarra - Pamplona

Pamplona, Spain

Location

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Instituto de Biomedicina de Sevilla

Seville, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Location

Study Officials

• Florent Malard, MD, PhD

  APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 25, 2021
• Study Start: March 25, 2022
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2025
• Last Updated: October 17, 2024

Record last verified: 2024-10

Locations

DE (5); AU (2); FR (16); IT (9); BE (5); ES (13)