Oral Pooled Fecal Microbiotherapy to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)

• ClinicalTrials.gov Identifier: NCT05762211
• Recruitment Status: Recruiting
• First Posted: March 9, 2023
• Last Update Posted: November 8, 2023
• Sponsor: MaaT Pharma
• Information provided by (Responsible Party): MaaT Pharma

Tracking Information

• First Submitted Date: January 27, 2023
• First Posted Date: March 9, 2023
• Last Update Posted Date: November 8, 2023
• Actual Study Start Date: October 31, 2023
• Estimated Primary Completion Date: October 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2023)

Overall survival [ Time Frame: 12 months post alloHCT ]

To compare the efficacy of MaaT033 with its placebo on OS at 12 months after alloHCT

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 27, 2023)

• Restoration of gut microbiota diversity [ Time Frame: 12 months post alloHCT ]
  To evaluate MaaT033 efficacy in gut microbiota diversity restoration using alpha-diversity (Richness index)
• grade 2-4 acute GvHD [ Time Frame: 6 months post alloHCT ]
  To evaluate the cumulative incidence of grade 2-4 acute GvHD within 6 months after alloHCT
• grade 3-4 acute GvHD [ Time Frame: 12 months post alloHCT ]
  To evaluate the cumulative incidence of grade 3-4 severe acute GvHD within 12+ + months after alloHCT
• Non-relapse mortality [ Time Frame: 12 months post alloHCT ]
  To evaluate the cumulative incidence of non-relapse mortality within 12 months after alloHCT
• Infectious-related mortality [ Time Frame: 12 months post alloHCT ]
  To evaluate the cumulative incidence of infectious-related mortality within 12 months after alloHCT
• GvHD-related mortality [ Time Frame: 12 months post alloHCT ]
  To evaluate the cumulative incidence of GvHD-related mortality within 12 months after alloHCT
• GRFS [ Time Frame: 12 months post alloHCT ]
  To evaluate GvHD-free relapse-free survival (GRFS) at 12 months after alloHCT
• Quality of life questionnaire [ Time Frame: 12 months post alloHCT ]
  To evaluate the Quality of Life (EORTC QLQ C30 questionnaire)
• Quality of life questionnaire [ Time Frame: 12 months post alloHCT ]
  To evaluate the Quality of Life (FACT-BMT questionnaire)
• Proportion of patients with severe infections [ Time Frame: 6 months after alloHCT ]
  To evaluate the proportion of patients with severe infections defined by NCI-CTCAE ≥ Grade 3 within 6 months after alloHCT
• Proportion of patients who have discontinued immune suppression therapies [ Time Frame: 12 months after alloHCT ]
  To evaluate the proportion of patients who have discontinued immune suppression therapies including standard of care GvHD prophylaxis and steroid treatment
• Time to platelet engraftment [ Time Frame: 12 months after alloHCT ]
  Time to the first of 3 consecutive days of absolute neutrophil counts ≥ 0.5 G/L after alloHCT
• Time to neutrophil engraftment [ Time Frame: 12 months after alloHCT ]
  Time to the first of 3 consecutive days of platelet counts ≥ 20 G/L after alloHCT
• Safety: incidence of AEs [ Time Frame: 12 months after alloHCT ]
  To evaluate MaaT033 safety

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Oral Pooled Fecal Microbiotherapy to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)
• Official Title: A Multi-center Randomized, Double Blinded Phase IIb Trial Evaluating Oral Pooled Fecal Microbiotherapy MaaT033 to Prevent Allogeneic Hematopoietic Cell Transplantation Complications (PHOEBUS Trial)
• Brief Summary: This randomized, placebo-controlled phase IIb study (PHOEBUS trial) aims to evaluate the activity of fecal microbiotherapy MaaT033 to improve survival through the prevention of transplant-related complications in eligible alloHCT patients
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Transplant Complication

Intervention

• Drug: Pooled allogeneic fecal microbiotherapy
  Capsule for oral use
  Other Name: MaaT033
• Drug: Placebo
  Capsule for oral use

Study Arms

• Experimental: Oral pooled fecal microbiotherapy - MaaT033
  3 capsules per day
  Intervention: Drug: Pooled allogeneic fecal microbiotherapy
• Placebo Comparator: Placebo capsule
  3 capsules per day
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 27, 2023): 387
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 15, 2027
• Estimated Primary Completion Date: October 31, 2026 (Final data collection date for primary outcome measure)

Eligibility 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
• Patients with polynuclear neutrophils > 0.5 G/L
• Patients having received wide spectrum antibiotics within the last 90 days prior to inclusion
• Karnofsky index ≥ 70%
• Availability of a sibling donor, an unrelated stem-cell donor or a familial haploidentical donor
• Written informed consent

Exclusion Criteria:

• Patients planned to receive a non-myeloablative conditioning regimen (2 Gray total body irradiation (TBI) +/- purine analog, fludarabine + cyclophosphamide or equivalent)
• Patients 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)
• Patients receiving a manipulated graft (in-vitro T-cell depletion)
• Patients planned to receive a conditioning regimen with alemtuzumab
• Patients planned to receive alloHCT with cord blood cells
• Patients planned to receive alloHCT from unrelated donor with >= 3/10 HLA-mismatches
• Patients receiving a large spectrum antibiotic at time of randomization
• Patients planned to receive vedolizumab or abatacept for GvHD prophylaxis
• Creatinine clearance <30 mL/min
• Bilirubin or amino-transferases abnormalities contra-indicating alloHCT
• Cardiac ejection fraction less than 40%
• Pulmonary impairment with <50% lung carbon monoxide diffusing capacity (DLCO)
• Pregnancy
• Confirmed or suspected intestinal ischemia
• Confirmed or suspected toxic megacolon or gastrointestinal perforation
• Any history of gastro-intestinal surgery in the past 3 months
• Any history of chronic digestive disease (Crohn's disease, ulcerative colitis, inflammatory bowel disease or other relevant digestive condition according to physician's judgement)
• Known allergy or intolerance to trehalose or maltodextrin
• Patients with EBV-IgG negative 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 patients such as: persons deprived of liberty, persons in Intensive Care Unit unable to provide informed consent prior to the intervention.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Emilie Plantamura; 0663590186; eplantamura@maat-pharma.com

Contact: Claire de Condé; cdeconde@maat-pharma.com

• Listed Location Countries: France, Germany

Administrative Information

• NCT Number: NCT05762211
• Other Study ID Numbers: MPOH08
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: MaaT Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: MaaT Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Florent Malard, MD, PhD; APHP

• PRS Account: MaaT Pharma
• Verification Date: November 2023