A multi-center randomized, double blinded phase IIb trial evaluating oral pooled fecal microbiotherapy MaaT033 to prevent allogeneic hematopoietic cell transplantation complications
- Trial ID
- 2022-501831-18-00
- Protocol
- MPOH08
- Sponsor
- MaaT PHARMA
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to compare the efficacy of **MaaT033** with its placebo on overall survival at 12 months following allogeneic hematopoietic cell transplantation (alloHCT) in patients with hematologic malignancies. This is clinically relevant as improving overall survival rates post-transplantation can significantly impact patient outcomes and quality of life.
Secondary objectives include:
- Evaluating GvHD-free survival at 12 months post-alloHCT.
- Assessing GvHD-free relapse-free survival at 12 months post-alloHCT.
- Evaluating overall survival and relapse-free survival at 24 months post-alloHCT.
- Assessing the efficacy of MaaT033 in correcting dysbiosis through microbiota composition changes.
- Evaluating the cumulative incidence of grade 2-4 and grade 3-4 severe acute GvHD at 6 months post-alloHCT.
- Assessing the cumulative incidence of chronic GvHD as per NIH Consensus Criteria at 6, 12, and 24 months post-alloHCT.
- Evaluating the cumulative incidence of non-relapse mortality, infection-related mortality, and GvHD-related mortality at 6, 12, and 24 months post-alloHCT.
- Assessing the proportion of subjects with severe infections defined by NCI-CTCAE ≥ Grade 3 within 12 months post-alloHCT.
- Evaluating the proportion of subjects who have discontinued immune suppression therapies, including standard GvHD prophylaxis and steroid treatment, at 6 and 12 months post-alloHCT.
- Assessing the neutrophil recovery rate at day 30 and the time to neutrophil recovery.
- Evaluating the platelet recovery rate at day 30 and the time to platelet recovery.
- Assessing the quality of life within 12 months post-alloHCT.
- Evaluating the nutritional status of the subjects.
Participants
The clinical trial involves a total of **14 participants** diagnosed with **hematologic malignancies** and undergoing allogenic hematopoietic cell transplantation. The study population includes both male and female subjects aged 50 years and older. Participants were selected based on specific criteria, including the presence of a hematologic malignancy requiring an alloHCT with a reduced toxicity or reduced intensity conditioning regimen. All participants have a Karnofsky index of 70% or higher, indicating a relatively stable general health status. Additionally, they have received wide spectrum antibiotics within the last 90 days prior to inclusion. The trial population includes individuals with access to a sibling donor, an unrelated stem-cell donor, or a familial haploidentical donor. The study also considers vulnerable populations, ensuring informed and written consent is obtained from all subjects or their legally acceptable representatives. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a **randomized**, **double-blind**, controlled Phase IIb study designed to evaluate the efficacy of the investigational product MaaT033, an oral pooled fecal microbiotherapy, in preventing complications associated with allogeneic hematopoietic cell transplantation (alloHCT) in patients with hematologic malignancies. The trial aims to compare the overall survival at 12 months post-transplantation between the treatment group receiving MaaT033 and the control group receiving a placebo. The study is expected to commence recruitment on January 1, 2023, and conclude by October 1, 2027.
Participants will be involved in the study for a maximum treatment period of 94 days, with the total duration of involvement extending up to 12 months for follow-up assessments. The trial includes several key visits: an initial **screening** visit to determine eligibility based on criteria such as age, presence of hematologic malignancy, and prior antibiotic use; randomization; and subsequent follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will assess the primary endpoint of overall survival, defined as the time from alloHCT to death from any cause.
Inclusion criteria require participants to be 50 years or older, have a Karnofsky index of at least 70%, and have access to a suitable stem-cell donor. Exclusion criteria are not specified in the provided data. Participants may be withdrawn from the study if they experience adverse events that compromise safety, fail to adhere to the protocol, or withdraw consent. The trial is not classified as low intervention, and it is part of the development process for obtaining marketing authorization for MaaT033.
Treatment
The clinical trial involves the administration of **MaaT033**, an experimental medication formulated as a **prolonged-release capsule**. The active substance in MaaT033 is **allogeneic faecal microbiota, pooled**, which is a structurally diverse substance. The medication is designed for **oral use** and is intended to be administered at a maximum daily dose of 0.42 grams, with a total maximum dose of 39.48 grams over a treatment period of up to 94 days. MaaT033 is developed by MAAT PHARMA and is classified under the category of Microbiome Ecosystem Therapy. The dosing schedule and participant compliance are monitored throughout the trial to ensure adherence to the protocol.
The study also includes a **placebo** group, where participants receive an inert coated capsule that contains no active microbiota. The placebo capsule is composed of a mix of coloring agents and partially pre-gelatinized corn starch encapsulated in a Hydroxypropyl methylcellulose capsule. The placebo is administered in the same pharmaceutical form and route as MaaT033, ensuring blinding and consistency in the trial design. The placebo serves as a comparator to evaluate the efficacy of MaaT033 in preventing complications following allogeneic hematopoietic cell transplantation.
Efficacy
The efficacy of the clinical trial will be assessed by comparing the **overall survival (OS)** at 12 months post-allogeneic hematopoietic cell transplantation (alloHCT) between the treatment group receiving MaaT033 and the placebo group. The primary endpoint for efficacy evaluation is the overall survival, defined as the time from the date of alloHCT to the date of death from any cause. This endpoint will be measured and analyzed to determine the effectiveness of MaaT033 in improving survival outcomes compared to placebo.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 50 years old.
- Presence of a hematologic malignancy for which an alloHCT is indicated with a reduced toxicity or reduced intensity conditioning regimen. Note: - Reduced toxicity or reduced intensity conditioning regimen is defined as any conditioning regimen that does not fit the definitions provided in the exclusion criteria. - Subjects planned to receive sequential protocols combining salvage chemotherapy with reduced intensity conditioning (RIC) and alloHCT can be included in the trial.
- Polynuclear neutrophils > 0.5 G/L.
- Received wide spectrum antibiotics within the last 90 days prior to inclusion. Note: Use of wide spectrum antibiotic is defined as use of at least 3 days of antibiotics within the last 90 days prior to inclusion, which is defined as randomization. For the list of wide spectrum antibiotics, refer to section 5.1 of Protocol.
- Karnofsky index ≥ 70%.
- Availability of a sibling donor, an unrelated stem-cell donor or a familial haploidentical donor.
- Signature of informed and written consent by the subject or by the subject’s legally acceptable representative for subjects under guardianship or trusteeship.
Exclusion Criteria
- Planned to receive a non-myeloablative conditioning regimen (2 Gray total body irradiation (TBI) +/- purine analog, fludarabine + cyclophosphamide or equivalent).
- Planned to receive a conventional myeloablative conditioning regimen (e.g. high dose cyclophosphamide and high dose TBI (≥10Gy); high dose busulfan (12.8 mg/kg IV) + high dose cyclophosphamide).
- Receiving a manipulated graft (in-vitro T-cell depletion).
- Planned to receive a conditioning regimen with alemtuzumab (CAMPATH®).
- Planned to receive alloHCT with cord blood cells.
- Planned to receive alloHCT from unrelated donor with ≥ 3/10 HLA-mismatches.
- Receiving a large spectrum antibiotic at time of randomization.
- Planned to receive vedolizumab or abatacept for GvHD prophylaxis.
- Documented creatinine clearance <30 mL/min.
- Documented bilirubin or amino-transferases abnormalities contra-indicating alloHCT. Note: Bilirubin > 3 x Upper normal limits (ULN), or Aspartate Transaminase / Alanine Transaminase (AST/ALT) > 5 x ULN to be considered as an exclusion criterion.
- Documented cardiac ejection fraction less than 40%. Note: The most recent cardiac ejection fraction measured in the previous 6 months prior screening documenting values below 40%.
- Documented pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO). Note: The most recent DLCO measured in the previous 6 months prior screening documenting values below 50%.
- Pregnancy and breastfeeding (urine or serum pregnancy test within 72 hours prior to randomization). Subjects (males and females of childbearing potential) should be willing to use an acceptable method of birth control such as hormonal contraception (progestogen-only may be sufficient), male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide for the course of the study (up to M12). A combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods) are also considered acceptable. A female is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 Months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 Months of amenorrhea, a single FSH measurement is insufficient.
- Documented confirmed or suspected intestinal ischemia.
- Documented confirmed or suspected toxic megacolon, bowel obstruction or gastrointestinal (GI) perforation.
- Any documented history of GI surgery in the past 3 months.
- Any documented history of chronic digestive disease (Crohn’s disease, ulcerative colitis (UC), inflammatory bowel disease or other relevant digestive condition according to physician’s judgement).
- Known allergy or intolerance to trehalose or maltodextrin.
- Negative EBV-IgG serology.
- Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.
- Vulnerable subjects such as: persons deprived of liberty, persons in Intensive Care Unit (ICU) unable to provide ICF prior to the intervention, persons under legal protection according to the national law.
- Other ongoing interventional protocol that might interfere with the current study’s primary endpoint. Note: Subjects previously included in interventional trials and no longer receiving the previous study medication but in follow-up, can participate in the PHOEBUS trial with a wash-out period of 5 half-lives of previous study medication as long as they meet all respective inclusion and none of the exclusion criteria.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Jan 2023 | 54 |
 France | Recruiting | 01 Jan 2023 | 139 |
 Germany | Recruiting | 01 Jan 2023 | 111 |
 The Netherlands | Recruiting | 01 Jan 2023 | — |
 Spain | Recruiting | 01 Jan 2023 | 42 |
| Netherlands | — | — | 28 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo is an inert coated capsule with no microbiota (active substance) inside. It is composed of a mix of coloring agents and partially pre-gelatinized corn starch in Hydroxypropyl methylcellulose capsule. | Placebo | N/A | — | — | — | N/A |
MaaT033 | Test | PROLONGED-RELEASE CAPSULE | ORAL USE | 0.42 | 94 | PRD8529751 |