Acute Pouchitis MedDRA version: 20.0 Level: PT Classification code 10036463 Term: Pouchitis System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Name: MH002
Product Code: MH002
Pharmaceutical Form: Capsule
INN or Proposed INN: There is no recommended International Nonproprietary Name (INN)
Current Sponsor code: MH002
Other descriptive
Sponsors
MRM Health NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female aged =18 years and =75 years - Documented history of RPC with IPAA for UC performed at least 12 months prior to enrollment - Confirmed diagnosis of Acute Pouchitis at Screening as defined by a modified Pouchitis Disease Activity Index (mPDAI) total score =5 and a mPDAI endoscopic subscore of =2 with symptoms not lasting >4 weeks - Females of childbearing potential must not be pregnant or lactating and must agree to take an acceptable effective (or highly effective) contraceptive method of birth control during the study - Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: - Chronic Pouchitis (=4 weeks of active Pouchitis) or antibiotic refractory Pouchitis - Pelvic sepsis, macroscopic ulceration(s) of the pouch exclusively on the IPAA anastomotic line, anal sphincter dysfunction, Crohn’s Disease of the pouch (known or suspected), Irritable Pouch Syndrome, isolated cuffitis, clinically significant pouch complications (stricture, fistula, anastomotic leak), diverting stoma, fecal incontinence - Evidence of systemic impact of Pouchitis, bacteremia or sepsis, fever (>37.8°C), or any active infection of the gastrointestinal (GI) tract (e.g., Clostridium difficile, Salmonella, Shigella, Yersinia, Campylobacter, Escherichia coli, Giardia lamblia, Cryptosporidium, Vibrio, Aeromonas, and Plesiomonas) - Medical history of any GI cancer - Any uncontrolled or unstable disorder (at the Investigator’s discretion, e.g., unstable Primary Sclerosing Cholangitis), including any clinically significant abnormality identified at Screening (e.g., safety lab parameters, physical exam) that may, according to the Investigator, put the subject at risk or interfere with the study procedures or reliability of study assessments to be done -Prior use (since IPAA) of any biological treatment, including ustekinumab, anti-TNF agents (e.g., infliximab or adalimumab) or anti-integrin antibodies (e.g., vedolizumab), or treatment with small molecules such as ozanimod or any Janus kinase inhibitor (e.g., tofacitinib) - Use of any topical treatment <4 weeks, any treatment with DiseaseModifying Antirheumatic Drugs (DMARDs) or other immunosuppressants, antibiotics, prebiotics or probiotics, or any investigational treatment <8 weeks, or Fecal Microbiota Transplantation <12 weeks prior to the Screening pouch endoscopy - Concomitant use, during the study, of any prohibited medication: any anti-inflammatory agents (e.g., 5-ASA or systemically available corticosteroids), biologicals, immunosuppressants, DMARDs, Live Biotherapeutic Products (LBPs, other than MH002), probiotics, prebiotics, antibiotics, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) (low dose aspirin excepted), investigational medicinal product (other than MH002) or investigational medical device, opioids or any rectally administered medication - Conditions linked to severe immunosuppression (e.g., related to human immunodeficiency virus, malignancies, liver cirrhosis, systemic chemotherapy) - 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, -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 - Any contraindication for pouch endoscopy - Subject not being able, according to the Investigator, to reliably meet study requirements, e.g., planned major surgery or travelling during the study, or alcohol/illicit drug dependence
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of MH002 in Acute Pouchitis subjects;Secondary Objective: To assess the mechanistic and clinical effects of MH002;Primary end point(s): • Incidence of treatment-emergent Adverse Events (AEs) and treatment-emergent Adverse Reactions (ARs), i.e., AEs occurring after treatment initiation that are considered to be at least possibly associated with MH002 treatment. • Laboratory safety parameters: hematology (platelet and RBC count, hemoglobin, hematocrit, WBC count & differential), chemistry (ALT, AST, GGT, LDH, ALP, bilirubin, creatinine, urea, uric acid, albumin, glucose, CRP, total cholesterol, triglycerides, creatin kinase, ionogram (Na, K, Ca, Cl, Phosphate)), urinalysis (blood, protein, glucose, pH (microscopy if clinically indicated)). Clinically significant lab abnormalities will be recorded as AEs;Timepoint(s) of evaluation of this end point: Visit 1, 2, 3, 4, 5 and 4 Safety follow-up phone calls | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Modified Pouchitis Disease Activity Index (mPDAI) total score, assessing signs and symptoms, and macroscopic appearance of mucosa for inflammation during endoscopy (using Mayo's Stool Frequency scores). • mPDAI subscores, i.e., endoscopic mucosal appearance, (Mayo) stool frequency, rectal bleeding, fecal urgency/abdominal cramps, fever. • Total number of ulcerations observed during endoscopy. • Rate of “clinical response”, defined as a mPDAI total score <5 and a decrease of =2 on the mPDAI total score at week 8. • Rate of “clinical remission”, defined as a mPDAI total score <5, a decrease of =2 in mPDAI total score, and a mPDAI endoscopic score <2 at week 8. • Physician’s Global Assessment (PGA). • Severity of urgency based on Urgency Scoring Scale (USS) (diary). • Daily (24h) stool frequency count (diary). • Blood and fecal inflammatory markers, including CRP, TNF-a, interleukin (IL)-1ß, IL-6 and IL-10 in blood and fecal calprotectin. • Histological assessment of mucosal biopsies using the PDAI histology and Geboes scoring system. • Differential expression of genes involved in the maintenance of mucosal barrier integrity and those involved in the modulation of inflammation and immunity;Timepoint(s) of evaluation of this end point: Visit 1, 2, 3, 4 and 5 | — |
Countries
Belgium, Italy
Contacts
Public ContactMH002-FIH Information Desk
MRM Health NV
Outcome results
None listed