Overview
Sponsor-declared trial summary
Pouchitis
We aim to investigate whether GM-CSF in combination with metronidazole and fosfomycin, applied topically in the pouch, can be used in patients with pouchitis. As pouchitis seems to mimic Crohn’s disease, and responds to therapy used in Crohn’s disease, we suspect that this combination therapy can target the bacterial d…
Key facts
- Sponsor
- Region Sjaelland, Reponex Pharmaceuticals A/S
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Immune System Diseases [C20]
- Trial duration
- 27 Sep 2024 → ongoing
- Decision date (initial)
- 2024-09-27
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-517764-38-00
- EudraCT number
- 2020-000609-10
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Efficacy
We aim to investigate whether GM-CSF in combination with metronidazole and fosfomycin, applied topically in the pouch, can be used in patients with pouchitis. As pouchitis seems to mimic Crohn’s disease, and responds to therapy used in Crohn’s disease, we suspect that this combination therapy can target the bacterial dysbiosis and inadequate immune response in pouchitis.
Conditions and MedDRA coding
Pouchitis
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- • Of any gender • Over 18 years of age • Have a previous diagnosis of ulcerative colitis • Have had IPAA surgery, and • Have been diagnosed with pouchitis • Be able to understand and complete study procedures as determined by the investigator • Be able to speak either Danish or English • Be able to comply with study procedures for the length of the study • Use a highly effective contraception method for the duration of the trial (until day 30 in Phase I and until day 37 in Phase II), such as implants, injectables, oral contraceptives, IUD (intrauterine device), sexual abstinence or vasectomized partner.
Exclusion criteria 1
- • Patients with a previous allergic reaction to GM-CSF, metronidazole or fosfomycin • Patients who are currently under antibiotic treatment or have received antibiotic treatment within the past 30 days • Patients currently pregnant or breastfeeding • Patients with ASA IV classification (American Society of Anesthesiologists physical status classification) • Patients with severe pulmonary disease • Patients with autoimmune thrombocytopenia • Patients with severe renal impairment (eGFR < 40 ml/min) • Patients with alcohol use disorder or history of drug abuse • Patients currently in treatment for any malignant or hematological disease • Patients with a previous history of cancer will be excluded from the study (except for patients with well-treated and stabile cancer after a control period of more than two years). • Patients with anticipated compliance problems as determined by the investigator
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Change in the pouchitis disease activity index (PDAI
Secondary endpoints 5
- Change in the clinical, endoscopic or histological PDAI
- Change in median WBC, CRP, creatinine and liver enzymes from before application of the study drug to 7 days after application of the study drug
- Change in microbial diversity in the pouch using 16S rRNA sequencing from before application of the study drug to 7 days after application of the study drug
- Safety: Determine serious adverse reactions or adverse reactions from the application of GM-CSF, metronidazole and fosfomycin in the pouch
- Assess the modulation of dendritic cells and inflammatory mechanisms using Nanostring nCounter analysis through mRNA expression and flow cytometry
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
SUB07797MIG · Substance
- Active substance
- Fosfomycin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRA-ABDOMINAL USE
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB08922MIG · Substance
- Active substance
- Metronidazole
- Pharmaceutical form
- INFUSION
- Route of administration
- INTRA-ABDOMINAL USE
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SUB09040MIG · Substance
- Active substance
- Molgramostim
- Pharmaceutical form
- LYOPHILISATE AND SOLVENT FOR SOLUTION FOR INJECTION
- Route of administration
- INTRA-ABDOMINAL USE
- Authorisation status
- Authorised
- ATC code
- - — -
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Region Sjaelland
- Sponsor organisation
- Region Sjaelland
- Address
- Lykkebaekvej 1
- City
- Koege
- Postcode
- 4600
- Country
- Denmark
Scientific contact point
- Organisation
- Region Sjaelland
- Contact name
- Ismail Gögenur
Public contact point
- Organisation
- Region Sjaelland
- Contact name
- Ismail Gögenur
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
Reponex Pharmaceuticals A/S
- Sponsor organisation
- Reponex Pharmaceuticals A/S
- Address
- Slotsmarken 12, 1 Th
- City
- Hoersholm
- Postcode
- 2970
- Country
- Denmark
Scientific contact point
- Organisation
- Region Sjaelland
- Contact name
- Ismail Gögenur
Public contact point
- Organisation
- Region Sjaelland
- Contact name
- Ismail Gögenur
Sponsor responsibilities
- Article 77 compliance
- Region Sjaelland
- Contact point sponsor
- Region Sjaelland
- Article 77 implementation
- Region Sjaelland
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 18 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2024-09-27 | 2024-09-27 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protokol Pouchitis Projekt | 3.7 |
| Protocol (for publication) | Protokol Pouchitis Projekt track changes | 3.7 |
| Recruitment arrangements (for publication) | Recruitment arrangements placeholder document | 1 |
| Subject information and informed consent form (for publication) | Deltagerinformation Pouchitis Projekt | 8 |
| Subject information and informed consent form (for publication) | Deltagerinformation Pouchitis Projekt track changes | 8 |
| Subject information and informed consent form (for publication) | Dine rettigheder som forsgsperson i forsg med medicin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SoPC Fosfomycin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | SoPC Metronidazole | 1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-09-09 | Denmark | Acceptable 2024-09-19
|
2024-09-27 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-10-07 | Denmark | Acceptable 2024-11-13
|
2024-11-14 |