Phase 2 Randomized Double‑Blind Placebo‑Controlled Study of Oral MH002 (10 000 vs 40 000 million CFU) in Mild‑to‑Moderate Ulcerative Colitis Inadequately Controlled with 5‑ASA

Trial ID: 2025-524682-24-00
Protocol: MH002-UC-202
Sponsor: Microbial Resource Management Health

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Diseases & Conditions

Colitis ulcerative

Objectives

The primary objective is to confirm the efficacy of MH002 in reducing disease activity in patients with mild‑to‑moderate Ulcerative Colitis insufficiently controlled with 5‑aminosalicylic acid, thereby addressing an unmet therapeutic need for improved disease control. Secondary objectives are to:

Confirm the ability of MH002 to induce clinical remission, providing a definitive therapeutic endpoint.
Assess the impact of MH002 on disease activity parameters, including symptoms, inflammatory markers, composite scores, and relevant biomarkers, to elucidate its effect on disease modulation.
Confirm the safety and tolerability profile of MH002, ensuring an acceptable risk‑benefit balance for patients.

Participants

The trial enrolled 95 participants diagnosed with Ulcerative Colitis. Eligible individuals were male or female, aged ≥ 16 years (≥ 18 years in the Czech Republic), and had a documented histologic diagnosis confirmed by endoscopic or radiographic findings at least three months before screening. All participants exhibited active mild‑to‑moderate disease (mMS 4–7, MES ≥ 2, Mayo RB score 1–2, stool frequency ≥ 1) with lesions extending ≥ 10 cm from the anal verge. Inclusion required either a stable oral 5‑ASA regimen for ≥ 4 weeks or documented failure/intolerance to an adequate 5‑ASA dose, and participants had to have completed the induction phase week‑12 visit without safety concerns. Women of childbearing potential were required to use an acceptable contraceptive method in accordance with local regulations. General health status was otherwise unrestricted, provided participants could comply with study procedures, including medication administration, visit attendance, patient‑reported assessments via personal devices, and stool sample collection.

Plans and Procedures

The study is a Phase 2, randomized, double‑blind, placebo‑controlled trial evaluating two oral dose levels of MH002 (10 000 million CFU and 40 000 million CFU per capsule) versus a matching placebo in patients with mild‑to‑moderate Ulcerative Colitis inadequately controlled by 5‑ASA. Eligible participants undergo a screening visit to confirm diagnosis, disease activity (modified Mayo Score 4–7, endoscopic subscore ≥2), lesion extent (≥10 cm), and stable 5‑ASA therapy; after meeting inclusion criteria, they are randomized in a 1:1:1 ratio to one of the three arms and begin a 12‑week treatment period. Study visits are scheduled at baseline (Day 0), Weeks 4, 8, and 12 for efficacy assessments (including centrally read Mayo endoscopic subscore) and safety monitoring; an end‑of‑study visit occurs at Week 12 to collect final data and study medication. Participants remain in the trial for approximately 12 weeks, with additional follow‑up for adverse events as required. Early termination may be initiated for any participant who experiences a treatment‑emergent serious adverse event, exhibits unacceptable laboratory abnormalities, fails to maintain compliance with study medication or visit schedule, or is withdrawn by the investigator for safety reasons. The overall recruitment period is projected from July 2026 to December 2028.

Treatment

The investigational product MH002 is supplied as an oral capsule containing 10,000 million colony forming units (CFU) of the active substance per capsule. The capsule is administered by the oral route according to the study dosing schedule and is intended for use in patients with mild-to-moderate ulcerative colitis insufficiently controlled with 5‑aminosalicylic acid.

A second dose strength of the investigational product MH002 is provided as an oral capsule containing 40,000 million CFU per capsule. This higher‑dose formulation is also administered orally as specified in the protocol for the same patient population.

The control arm utilizes a matching placebo capsule that is identical in appearance to the active capsules but contains no active substance. It is administered orally in accordance with the same schedule as the active arms.

All study medications are dispensed in blister packs, and dosing is recorded in participant diaries. Compliance is monitored through pill count at each study visit and review of diary entries to ensure adherence to the prescribed regimen.

Efficacy

Efficacy will be evaluated primarily by the change from baseline in the centrally‑assessed Mayo endoscopic subscore measured at Week 12.

Key secondary efficacy parameters include clinical remission at Week 12, defined by a modified Mayo Score ≤2 with all subscores ≤1, a Rectal Bleeding subscore of 0, and a stool frequency subscore not exceeding baseline; histologic improvement assessed by the Robarts’ Histopathology Index; the median percent change from baseline in fecal calprotectin; change from baseline in the UC‑100 composite score; and change from baseline in the PRO‑2 patient‑reported outcome score derived from electronic diary entries.

Endoscopic assessments will be performed by a blinded central reader using standardized imaging protocols. Histologic specimens will be evaluated by a central pathology laboratory employing the RHI scoring system. Fecal calprotectin concentrations will be quantified using a validated laboratory assay. PRO‑2 scores will be calculated from patient‑entered data captured in an electronic diary. All efficacy endpoints will be measured at baseline and at Week 12, and changes from baseline will be analyzed according to the study statistical analysis plan.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Male or female aged ≥16 years (≥18 years for Czech Republic) of age at time of signing the consent/assent. Enrollment of participants <18 years old should only occur if acceptable by local laws and regulations.
Documented diagnosis (histologic diagnosis and either endoscopic or radiographic diagnosis) of UC at least 3 months prior to Screening (a biopsy report supporting the histologic diagnosis must be available).
Diagnosis of active mild-to-moderate UC at Screening as defined by an mMS of 4 to 7, including a MES ≥2 (confirmed by central reading), a Mayo RB score of 1 or 2, and a Mayo Stool Frequency score ≥1.
UC lesions extending ≥10 cm from the anal verge.
Participant must either: • receive a stable dose of orally administered 5 ASA ≥4 weeks prior to randomization and continue the same regimen during the entire study (including OLE phase), or • have failed, due to insufficient efficacy, oral 5-ASA induction treatment at a minimum dosage of 2 g/day for at least 6 weeks or have failed oral 5-ASA maintenance treatment at a minimum dosage of 2 g/day, or • have a documented intolerance or poor tolerance to an aminosalicylic acid treatment, including 5-ASA, or be contra-indicated to receive 5 ASA treatment per local labeling
Participant must provide written informed consent or assent.
In countries not allowing females of childbearing potential (FOCBP) to participate without an acceptable contraceptive method, the FOCBP must agree to abide to local requirements and eg, use at least an acceptable method of contraception until the end of treatment
OLE 1. Having successfully completed the Week 12 visit of the Induction Phase ie, having demonstrated acceptable compliance per the Investigator’s discretion and having completed patient-reported assessments.
OLE 2. Participant must be willing and agree to abide to the study requirements, including compliance with study treatment administration, attendance to study visits, performing assessments, including collection of patient-reported data via their personal device (BYOD), and providing stool samples.
OLE 3. Having had no significant safety concerns during the Induction Phase, as determined by the Investigator.
OLE 4. FOCBP must agree to continue using an acceptable contraceptive method in countries where this is required

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Exclusion Criteria

Diagnosis of Crohn’s disease, undetermined colitis, ischemic colitis, fulminant colitis, or toxic megacolon.
Evidence of a clinically significant, active infection of the gastrointestinal tract or of any other organ system at Screening, unless deemed benign. Clostridium difficile infection should have had adequate treatment and a negative toxin test prior to Screening endoscopy.
Severe UC (mMS>7), meeting modified Truelove Witts' criteria and/or RB score of 3, participant with ulcerative proctitis only, or participant in whom colitis is most severe in the transverse colon or ascending colon, or if any hospitalization is planned at the time of Screening
Total colectomy, stoma or ileo-anal pouch, or history of extensive colonic resection leaving less than 30 cm of colon
Presence of intra-abdominal fistula, abscesses, diverticulitis, or gastrointestinal bleeding unrelated to UC
History of colon carcinoma or high-grade dysplasia
Previous use of any advanced UC treatment, including any anti-tumor necrosis factor, anti-integrin or anti-interleukin (IL)-12/23 agent, anti-IL23, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators.
Use of sulfasalazine ≤4 weeks prior to randomization.
Use of corticosteroids or any disease-modifying antirheumatic drug, including thiopurines, ≤6 weeks prior to randomization into the study, except for a stable, low dose of oral corticosteroids (≤10 mg prednisolone/day) for at least 2 weeks prior to Screening colonoscopy and up to at least the Week 12 visit.
Use of antibiotics (except for local use), prebiotics, or probiotics ≤4 weeks prior to randomization or anticipated during study participation, or concomitant, chronic use of an antidiarrheal drug, or concomitant use of any rectal treatment.
Use of fecal microbiota transplantation ≤52 weeks prior to randomization
Treatment with another investigational drug or intervention within 30 days prior to Screening, or within 5 times the elimination half-life of the investigational drug (whichever is longest).
Any immunocompromised state, including eg, active human immunodeficiency virus infection, malignancies, liver cirrhosis, systemic chemotherapy).
Leukopenia (total white blood cell count <3000/µL) and/or neutropenia (absolute neutrophil count <1000/µL), anemia (hemoglobin <10.0 g/dL), thrombocytopenia (peripheral blood platelet count <100 × 10E9/L), and/or any coagulation disorder with significantly increased risk of bleeding. For any of these exclusion criteria at Screening, 1 retest is allowed.
Ongoing or recent (<3 months) severe renal disease or insufficiency as manifested, eg, by medical history and/or clinical examination and/or (calculated or measured) glomerular filtration rate ≤60 mL/min.
Ongoing or recent (<3 months) advanced hepatic dysfunction defined as a Child Pugh score ≥10 (Class C) or increase ≥2 times the upper limit of normal in AST, ALT, total bilirubin (TB), prothrombin time (PT), or international normalized ratio (INR).
Clinically significant bone marrow disease if progressive or not controlled, or any history of solid organ or bone marrow transplantation.
Any protein-losing enteropathy (any cause), any granulomatous disease, any systemic (autoimmune) disease if progressive or not controlled (uncomplicated and well-controlled diabetes mellitus is allowed).
Active intravenous drug abuse or alcohol abuse disorder as assessed by the Investigator
Pregnancy or lactation at study entry
Participants who are inappropriate for the study per the Investigator’s discretion, including: • Participants with any other condition, disorder, or disease that in the Investigator’s judgment would make the participant unsuitable for inclusion in the study • Participants with a hypersensitivity to drugs with a similar mechanism as well as known allergy/hypersensitivity to any component of the study treatment, including any of the excipients • Participants who in the opinion of the Investigator are not likely to complete the study for whatever reason • Participants who are unwilling or unable to comply with protocol requirements, including eg, complete the full course of study treatment per schedule, attend study visits and all required assessments/investigations, and complete all questionnaires and e-diary using their personal device or study-provided device
An employee (or a relative of) of the Investigator, study center, contract research organization, or Sponsor