E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10009900 |
E.1.2 | Term | Colitis ulcerative |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the safety and tolerability of MH002 in subjects with mild to moderate ulcerative colitis (UC) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effect on disease activity of MH002 in UC • To evaluate the mechanistic effects of MH002 in UC
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female aged ≥18 years and ≤75 years, 2. 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), 3. Confirmed diagnosis of mild to moderate UC at Screening as defined by an MMS ≥4 but <8 and MES of 2 or 3(Central reading). 4. Left-sided colitis lesions ≥10 cm, 5. Subject should be receiving a stable dosing (topical or systemic) regimen of 5-ASA (eg, Asacol, Pentasa, Lialda, Apriso, Delzicol) ≥4 weeks prior to randomization and continue on that same regimen during the study, 6. Females of childbearing potential (FOCBP) must agree to utilize an acceptable effective or highly effective contraceptive method of birth control, eg, use a male or female condom with or without spermicide or any prescription hormonal contraceptive, during study participation at a minimum, and 7. Subject should provide written informed consent |
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E.4 | Principal exclusion criteria |
1. Diagnosis of Crohn’s Disease, undetermined colitis, ischemic colitis, fulminant colitis, or toxic megacolon, 2. Evidence of a clinically significant, active infection of the gastrointestinal tract (eg, Salmonella, Shigella, Yersinia, Campylobacter, Escherichia coli, Giardia lamblia, Vibrio, Aeromonas, Plesiomonas, Cryptosporidium, and toxigenic Clostridium difficile) or of any other organ system at Screening, unless deemed benign (eg, mild common cold), 3. Ulcerative proctitis involving only the rectum, 4. Severe UC as per modified Truelove Witts’ criteria or patients in whom colitis is most severe in the transverse colon or ascending colon, 5. Total colectomy, stoma or ileo-anal pouch, or history of extensive colonic resection leaving less than 30 cm of colon, 6. Presence of intra-abdominal fistula, abscesses, diverticulitis, or gastrointestinal bleeding unrelated to UC, 7. History of colon carcinoma or high-grade dysplasia or absence of total endoscopy ≤18 months in a subject suffering from UC ≥8 years, 8. Previous use of any anti-TNF (eg, Infliximab), anti-integrin antibodies (eg, Entyvio) or Janus kinase inhibitors (eg, tofacitinib), 9. Use of sulfasalazine ≤4 weeks prior to randomization into the study, 10. Use of corticosteroids or any disease-modifying antirheumatic drug (DMARD), including thiopurines (eg, Imuran) ≤6 weeks prior to randomization into the study, except for a stable, low dose of oral corticosteroids (≤8 mg methylprednisolone/day or equivalent) for at least 2 weeks prior to colonoscopy and remaining on the same dose up to Visit 8/EDV, 11. Conditions linked to severe immunosuppression (eg, human immunodeficiency virus, malignancies, liver cirrhosis, systemic chemotherapy), 12. Leukopenia (total white blood cell count <3500/μL) and/or neutropenia (absolute neutrophil count <1500/μL), 13. Severe anemia (hemoglobin <10 g/dL), 14. Thrombocytopenia (peripheral blood platelet count <100 × 109/L), or any coagulation disorder with significantly increased risk of bleeding, 15. Ongoing or recent (<3 months), significant renal disease or insufficiency as manifested, eg, by medical history and/or clinical examination and/or (calculated or measured) glomerular filtration rate significantly outside normal limits for age and sex, 16. Ongoing or recent (<3 months), significant hepatic disease as manifested by medical history and/or clinical examination and/or an increase in 2.5 × the upper limit of normal for alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, or alkaline phosphatase, 17. Clinically significant bone marrow disease if progressive or not controlled, 18. Any protein-losing enteropathy (any cause), 19. Any systemic (autoimmune) disease if progressive or not controlled (uncomplicated and well-controlled diabetes mellitus is allowed), 20. Any granulomatous disease, 21. Increased risk of developing infectious endocarditis including: - Prosthetic cardiac valves including transcatheter-implanted prostheses and homografts, - Prosthetic material used for cardiac valve repair such as annuloplasty rings and chords, - Previous infectious endocarditis, and - Unrepaired cyanotic congenital heart disease or repaired congenital heart disease, with residual shunts or valvular regurgitation at the site of or adjacent to the site of a prosthetic patch or prosthetic device 22. Any history of solid organ or bone marrow transplantation, 23. Use of antibiotics (except for local use), prebiotics, or probiotics ≤4 weeks prior to randomization or anticipated during participation, concomitant, chronic use of an antidiarrheal drug, or concomitant use of any rectal treatment (5-ASA excepted), 24. History of intravenous drug abuse, 25. Alcohol abuse disorder as assessed by the Investigator, 26. Pregnancy or lactation, 27. Treatment with another investigational drug or intervention within 30 days prior to Screening, and 28. Subjects who to the Investigator’s discretion are inappropriate for the study, including: - Subjects with any other condition, disorder, or disease that in the Investigator’s judgment would make the subject unsuitable for inclusion in the study (eg, recent major surgery, severe disorder or disease, state of malnutrition, or contraindication for colonoscopy with biopsy), - Subjects who in the opinion of the Investigator are not likely to complete the study for whatever reason (eg, short life expectancy), and - Subjects who are unwilling or unable to comply with protocol requirements, eg, complete the full course of study treatment per schedule, attend study visits and all required assessments/investigations, and complete an electronic diary (eg, planned surgery or moving abroad) - An employee of the Principal Investigator, clinical center, contract research organization or Sponsor. A relative of an employee of the clinical center, the investigators, contract research organization, or the Sponsor. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of treatment-emergent adverse events.(TEAEs). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 2, week 4, week 8, week 10, week 12, week 16 and phone calls: Day 3, Day7(8) and week 19 |
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E.5.2 | Secondary end point(s) |
To evaluate the effects on disease activity of MH002 in UC • 3-item Modified Mayo Score (MMS): sum of the Mayo symptom subscores for stool frequency and rectal bleeding and centrally assessed Mayo Endoscopic Score (MES), ie, without the Physician’s Global Assessment of disease activity, • MMS subscores, ie, stool frequency, rectal bleeding, and MES, • Rate of ‘clinical response’, defined as a decrease of ≥3 points on the MMS and/or a decrease of ≥1 on the stool frequency subscore + a decrease of ≥1 on the rectal bleeding subscore, • Rate of ‘clinical remission’, defined as MMS ≤2 and with all MMS subscores ≤1 and a rectal bleeding subscore of 0, • Histologic scores (Nancy Index, Geboes Score, and Robarts Histopathology Index) of colonic biopsies, and
To evaluate the mechanistic effects of MH002 in UC: • Changes in stool consistency based on Bristol Stool Form Scale. • The differential expression of genes in the context of barrier integrity, including tight junction, mucin, cell proliferation, and differentiation genes (transcriptomics based on RNA-sequencing of colonic biopsies). • The differential expression of genes in the context of modulation of inflammation and immunity (transcriptomics based on RNA-sequencing of colonic biopsies). • Extent of inflammation by evaluating biomarkers in blood (including C-reactive protein, tumor necrosis factor α, and interleukins) and in feces (fecal calprotectin). • Changes in the composition of the fecal microbiome (metagenomics based on deep sequencing of fecal samples). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |