PARADOX study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Phenomena and Processes [G] - Immune system processes [G12], Diseases [C] - Digestive System Diseases [C06]

Trial duration

15 Nov 2024 → 6 Jan 2026

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ECCO

External identifiers

EU CT number

2024-515278-28-00

EudraCT number

2021-003913-21

WHO UTN

U1111-1309-1815

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy

The main objective of this study is to evaluate molecular effects in patients with moderate-to-severe ulcerative colitis refractory to medical therapy, more specifically:
- Clinical, endoscopic, histological and ultrasonographic disease activity
- Mucosal blood flow, oedema and oxygen delivery
- Mucosal immune cell populations
- Mucosal transcriptional profiles, mainly hypoxia inducible factor (HIF) dependent cascades
- Mucosal cytokine profiles
- Drug penetration
- Mucosal stem cell populations important to mucosal healing

Secondary objectives 1

1. The secondary aim of this study is to evaluate dose-response relationship and feasibility of hyperbaric oxygen therapy in moderate-to-severe ulcerative colitis refractory to medical therapy.

Conditions and MedDRA coding

ulcerative colitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. In order to be eligible to participate in this study, a subject enrolled in the treatment groups must meet all of the following criteria: All patients in treatment groups: 1. Documented diagnosis of UC ≥ 4 months prior to entry into the study, confirmed with endoscopy and pathology results available in the source documents 2. Moderately to severely active UC as defined by a total MAYO score of ≥ 5 and a MAYO ES of ≥ 2 determined within 7 days of starting HBOT treatment 3. Subjects must have failed or be intolerant (discontinued the medication due to an adverse event as determined by the investigator) of the following treatments: a. Oral corticosteroids b. Azathioprine or 6-mercaptopurine c. Anti-TNF therapy: infliximab, adalimumab or golimumab d. vedolizumab e. Current treatment with ustekinumab (or another p19 inhibitor in a clinical trial) or small-molecule therapy (e.g., tofacitinib) 4. Current treatment with a stable dose of ustekinumab or tofacitinib (>12 weeks of stable dose and interval of ustekinumab and >6 weeks of tofacitinib) 5. Age 16 or older 6. Approved for compassionate use of hyperbaric oxygen therapy by the treating physician and the health insurance company 7. In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements. 8. The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 9. Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout week 26. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).

Exclusion criteria 1

1. A subject will not be eligible for participation in this study if any of the following criteria apply: 1. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis or clinical findings suggestive of Crohn’s disease 2. Subjects without previous treatment for UC (i.e., treatment-naïve) 3. Subjects at imminent need of surgery as judged by the treating clinician 4. Subjects with evidence of colonic adenomas or dysplasia. However, subjects with prior history of adenomatous polyps will be eligible if the polyps have been completely removed and the subjects are free of polyps at baseline 5. Subjects who have positive stool examinations for enteric pathogens (including Salmonella, Shigella, Yersinia, Campylobacter, C. difficile) detected by stool analysis within 2 weeks prior to enrollment pathogenic ova or parasites, at baseline 6. Patients with an ostomy 7. Unfit for hyperbaric oxygen therapy as assessed by the hyperbaric physician. 8. Contra-indication for endoscopy 9. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer 10. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures 11. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures 12. Patients unable to attend all study visits 13. Patients with a history of non-compliance with clinical study protocols

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Co-primary endpoints include: methylome of peripheral blood and mucosal monocytes, mucosal single transcriptomics, cytokine profiles, microbiome, drug concentrations and blood flow

Secondary endpoints 1

1. - Response after completion of HBOT and at week 12 post-treatment defined as a reduction in complete MAYO score of 3 points AND at least 1 point reduction in the MAYO ES WITHOUT escalating therapy such as dose escalations, switching to another drug, adding corticosteroids or colectomy, - Clinical disease activity assessed by the PRO-2 score during treatment at day 2, 4, 6 and the last day of treatment, for the group with 20 and 30 sessions: day 10 and 14 and the group with 30 sessions: day 20,

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation

Stichting Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Stichting Amsterdam UMC

Contact name

Lieven Mulders

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

Lieven Mulders

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications