Investigating the safety, feasibility, and optimal dose of Adalimumab-680LT in IBD – GUIDE 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] - Immune System Diseases [C20], Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 Mar 2024 → 6 Jan 2026

Decision date (initial)

2024-01-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

University Medical Center Groningen

External identifiers

EU CT number

2023-508391-11-00

ClinicalTrials.gov

NCT06117423

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Dose response

To evaluate the safety of adalimumab-680LT through monitoring vital signs, the injection site and evaluating possible tracer-related (severe) adverse events (SAE/AEs) and suspected unexpected serious adverse reactions (SUSARs).
To investigate the feasibility of using fluorescence molecular endoscopy (FME) and ex vivo FMI to detect adalimumab-680LT 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 adalimumab 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 adalimumab mucosal target cells.

Conditions and MedDRA coding

Inflammatory Bowel Disease (IBD)

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 and biochemically active disease as defined by a fecal calprotectin > 60 µg/g (measurement within the last 6 weeks before inclusion
3. Patients must be eligible for adalimumab therapy
4. Age of 18 years
5. Written informed consent.
6. Clinical indication for an endoscopic procedure

Exclusion criteria 6

1. A female study patient who is pregnant or provides breastfeeding will be excluded from participation in this study
2. Medical or psychiatric conditions that compromise the patient’s ability to give informed consent
3. Prior anti-TNF therapy in the last 6 weeks before inclusion
4. A female study patient of premenopausal age who does not use any reliable form of contraception at the time of adalimumab-680LT administration and the following 10 weeks
5. Active extra gastrointestinal manifestations of Crohn’s disease (e.g. uveitis or pyoderma gangrenosum at vital locations)
6. Previous treatment with adalimumab and detectable anti-adalimumab antibodies levels

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Monitoring of the vital signs before and after tracer administration and evaluating possible (severe) adverse events (SAE & AEs). 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. Comparison of in vivo fluorescence images, MFIs of biopsies, the MDSFR/SFF measurements, fluorescence microscopy results, and tracer concentrations inside biopsies before and after at least 14 weeks of adalimumab treatment.
2. Quantification of MDSFR/SFF measurements in inflamed tissue compared to measurements in non-inflamed tissue. Positive correlation between MDSFR/SFF measurements and dose/inflammation severity?
3. Histologically ascertained tissue types (qualitative): • Normal (non-inflamed) ileal, colon and rectal tissue. • Inflamed ileum, colon and rectum tissue. • Random ‘’high-fluorescent’’ tissue • Random ‘’Non-fluorescent’’ tissue
4. Fluorescence (confocal) microscopy with additional use of immune panels and spatial transcriptomics analysis (before and after at least 14 weeks of adalimumab treatment). Measurements of the adalimumab-680LT concentration by light-sheet microscopy after tissue clearing, insights in adalimumab-target cells and presence of immune cells inside the biopsies and blood samples by flow cytometry and assessment of tracer stability by Western Blot.

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

Application history

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