Immune-Related Rheumatological and neurological Adverse Events study.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

Participant type

Healthy volunteers, 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] - Investigative Techniques [E05], Diseases [C] - Neoplasms [C04]

Trial duration

5 May 2023 → ongoing

Decision date (initial)

2024-12-03

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516631-27-00

EudraCT number

2021-005613-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Diagnosis

To characterize common and distinct immunological pathomechanisms in rheumatological and
neurological immune-related adverse events (R- and N-irAEs) induced by checkpoint
inhibitors (ICI) compared to immune-mediated inflammatory diseases (IMID’s).
Co-primary objective: To collect and define data on diagnosis and management of
rheumatological and neurological irAE’s in patients with cancer starting therapy with
checkpoint inhibitors.

Secondary objectives 5

1. To assess frequency of flares and course of underlying autoimmune disease activity in patients with rheumatological or neurological immune mediated inflammatory diseases (IMIDs) starting ICI
2. To characterize immunophenotypes in blood and other available biomaterials as well as longitudinal changes herein in patients developing rheumatological or neurological irAEs, compared to patients with classical IMIDs.
3. To identify biomarkers into actionable diagnostic/ predictive tests in IMID’s and R-/N-irAE’s
4. To assess immunohistochemical profiles (blood, synovial fluid, tissue) in patients with irAE arthritis compared to patients with classic de novo rheumatoid arthritis
5. To compare whole-body [18F]FDG PET/CT in irAE arthritis and de novo rheumatoid arthritis in the distribution and extent of inflammatory activity in joints and other tissues.

Conditions and MedDRA coding

Cancer (all types)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. ≥18 yr.
2. Diagnosed with any oncological disease with or without pre-existing auto-immune disease
3. Starting with ICI therapy (ICI therapy defined as treatment with anti-PD1, anti-PDL1, anti-CTLA-4 or newly registered immune checkpoint therapies, either in mono- or combination therapy)

Exclusion criteria 1

1. Previous treatment with ICI therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The differentiation and quantification of the (relative) frequency of different immune-cell subsets* in the peripheral blood (and potentially other biomaterials)
2. The quantification of immune activity of the defined immune-cell subsets* by performing in vitro functional assays.
3. The evaluation of the specific incidence, serological profiles and response to treatment of patients both with and without preexisting disease and starting ICI therapy and those developing irAE’s.

Secondary endpoints 4

1. Disease activity and its progression over time were evaluated using disease-specific scoring metrics and the frequency, time of onset, duration, and severity (grade) of flares were recorded.
2. The absolute change and fold-change in frequency of different immune-cell subsets* in the peripheral blood (and potentially other biomaterials) of R-irAE or N-irAE patients during immunosuppressive therapy.
3. The immunohistochemical phenotype (determined in blood, synovial fluid and synovial tissue) of specifically R-irAE arthritis compared to classical RA.
4. The qualitative comparison of whole body [18F]FDG PET/CT imaging of R-irAE arthritis patients with classical RA patients. The study endpoints are defined as: the standardized uptake value (SUV) metrics (SUVmax, SUVpeak and SUVmean) of the joints, muscles/muscle insertions and lymphoid organs and the biodistribution of the tracer - SUV metrics of certain organs at interest, such as the liver, spleen, bone marrow, heart, kidneys etc.

Investigational products

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

Test 4

Auxiliary 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

Principal investigator

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

Principal investigator

Locations

1 EU/EEA country · 4 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 10 files

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

Application history

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