Investigating the safety, feasibility, and optimal dose of risankizumab-800CW in IBD - NAVIGATE study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

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

8 Nov 2024 → 19 May 2026

Decision date (initial)

2024-09-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

University Medical Center Groningen

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Therapy

To evaluate the safety of risankizumab-800CW through monitoring vital signs, the injection site and evaluating possible tracer-related (severe) adverse events (SAE/AEs) and suspected unexpected serious adverse events (SUSARs).
To investigate the feasibility of using fluorescence molecular endoscopy (FME) and ex vivo FMI to detect risankizumab-800CW signals and to determine their most optimal imaging dose.

Secondary objectives 4

1. Investigate a potential correlation of in vivo and ex vivo fluorescence signal intensities and target saturation to clinical response/remission after 14 weeks of risankizumab therapy regimen in patients with IBD.
2. Quantify the fluorescence signals of the tracer in vivo by using single-fiber reflectance/single-fiber fluorescence (MDSFR/SFF) spectroscopy and correlate these measurements to tracer dose, in vivo fluorescence intensities and inflammation severity.
3. To correlate ex vivo fluorescence signals to inflammation severity and tracer dose based on histopathological examination inside the obtained biopsies.
4. To assess tracer stability, tracer distribution and tracer concentration, and to identify the composition of immune cells ex vivo to learn more about risankizumab mucosal target cells

Conditions and MedDRA coding

Inflammatory Bowel Disease (IBD)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Established IBD diagnosis (UC or CD).
2. Active disease: clinically active disease of the bowel is defined clinically as at least mild activity using dedicated scoring indices or biochemically active disease as defined by a fecal calprotectin > 60 µg/g
3. Patients must be eligible for risankizumab therapy.
4. Age of 18 years.
5. Written informed consent.
6. Clinical indication for an endoscopic procedure.
7. For female subject who are of childbearing potential, are premenopausal with intact reproductive organs, or are less than 2 years postmenopausal, a negative pregnancy test (urine or blood test) must be available.

Exclusion criteria 5

1. A female study patient who is pregnant or provides breastfeeding
2. A female study patient of premenopausal age who does not use any reliable form of contraception at the time of risankizumab-800CW administration and the following 10 weeks
3. Medical or psychiatric conditions that compromise the patient’s ability to give informed consent
4. Prior anti-IL23-specific therapy (IL23/IL12 combination therapy is not an exclusion criteria)
5. Active extra gastrointestinal manifestations of Crohn’s disease (e.g. uveitis or pyoderma gangrenosum at vital locations)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Monitoring of the vital signs before and after tracer administration and evaluating possible (severe) adverse events (SAE & AEs).
2. Visual evaluation during FME (visible signal yes/no), TBR and CNR calculations, mean fluorescence intensities (MFIs) of biopsies, MDSFR/SFF measurements and fluorescence/ light sheet microscopy.

Secondary endpoints 4

1. Analysis of in vivo fluorescence images and quantification of fluorescence signals in real-time with spectroscopy, and compare this to endoscopic/histologic inflammation score. We semi-quantify the fluorescence signal in FFPE-biopsies of mucosal tissue. These measurements are compared to the in vivo results of the same bowel section. For patients on treatment, we will look for a possible correlation of in and ex vivo quantified fluorescence and endoscopic/histologic response to risankizumab.
2. Fluorescence signal will be quantified by spectroscopy during endoscopy in all FME inspected bowel segments. The measurements will be compared within all dose groups to determine the optimal dose. Furthermore, spectroscopy measurements will be correlated with fluorescence intensities visualized using the FME camera. Finally, these measurements will be compared with inflammation severity to draw any conclusions about risankizumab distribution into inflamed or non-inflamed tissue.
3. In vivo and ex vivo spectroscopy measurements will be plotted against tracer dose and endoscopic/histopathological inflammation scores. The gastroenterologist evaluates the endoscopic inflammation score during the endoscopy. The histopathological score is determined by an expert pathologist based on an H&E staining of the FFPE biopsies. We hypothesize a positive correlation between the fluorescence signal and the tracer dose and between the fluorescence signal and the inflammation scores.
4. SDS-PAGE with protein extracts of biopsies is used to prove that the fluorescence signal measured originated from the intact tracer. 3D ex vivo fluorescence analysis on biopsies is performed to assess the concentration of risankizumab-800CW in the intact biopsies. Fluorescence microscopy is performed to visualize the tracer signal and perform additional immunofluorescence staining for different immune cells to identify the immune cell type of risankizumab-800CW positive cells.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Wouter B. Nagengast

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Wouter B. Nagengast

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 9 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