Inhibition of Mast cell Activation in AtheroScleroTic lesions using an Anti-IgE antibody approach (MAST)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Utrecht

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

completed 14 Nov 2024

Decision date (initial)

2024-08-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMW

External identifiers

EU CT number

2024-513581-19-00

EudraCT number

2019-002452-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine whether short anti-IgE treatment with an anti-IgE monoclonal antibody (omalizumab) can limit intraplaque mast cell activation in atherosclerotic plaques, acquired by a carotid endarterectomy.

Secondary objectives 7

1. To investigate whether omalizumab has an effect on the local inflammatory status of atherosclerotic plaque by measuring T cell subsets, M1/M2 macrophages, neutrophiles and B-cells in the immune cell suspension obtained from the plaque using flow cytomtry.
2. To determine if treatment with omalizumab results in a systemic reduction of mast cell activation by measuring blood tryptase levels.
3. To identify changes in the extent of inflammation by analyzing infection parameters (e.g. complete blood count, hs CRP, IL-1B and IL-6) after treatment with either placebo or omalizumab.
4. To analyze plaques for plaque phenotype such as necrotic area, cellular composition and stability parameters using histology.
5. To investigate the change in serum IgE levels in patients after treatment with either placebo or omalizumab.
6. To determine the activation status of basophils using a BAT assay after treatment with either placebo or omalizumab.
7. To determine if omalizumab increases the occurence of arterial thromboembolic events.

Conditions and MedDRA coding

Carotid artery stenosis

Regulatory references

Scientific advice from competent authorities

METC Utrecht

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Patient is 18 years or age or older.
2. Patient is able and willing to give their consent and sign an informed consent.
3. Patient has a symptomatic or asymptomatic atherosclerotic carotid artery stenosis of at least 50% narrowing of the lumen (calculated by using criteria equivalent to the NASCET method) wherefore revascularisation through carotid endarterectomy is plannend routinely.

Exclusion criteria 3

1. Previous anaphylactic reaction (e.g. food allergy, medication such as antibiotics)
2. Previous carotid endarterectomy (CEA) or carotid artery stenting (CAS) in the ipsilateral artery.
3. Patients with severe asthma or chronic urticaria which are treated or have been treated with omalizumab subcutaneously.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary study endpoint is the % of mast cell activation, which can be measured with flow cytometry.

Secondary endpoints 8

1. The effect of omalizumab on the level of inflammation of patients with atherosclerosis by measuring the percentage of inflammatory cells (T cell subsets, M1/M2 macrophages, neutrophils, B-cells) in the immune cell suspension obtained from the plaque using flow cytometry.
2. The effect of omalizumab treatment on circulating IgE levels determined by ELISA.
3. The effect of omalizumab on tryptase levels (and thereby on systemic mast cell activation).
4. The effect of omalizumab on plaque levels of tryptase and chymase.
5. The effect of omalizumab on the activation status of basophils by using a BAT assay.
6. The effect of omalizumab on plaque phenotype such as necrotic area, cellular composition and stability parameters using histology.
7. The effect of omalizumab on circulating white blood cell count, hsCRP, IL-1B and IL-6.
8. As a secondary safety parameter the occurence of arterial thromboembolic events will be documented.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Utrecht

Sponsor organisation

Universitair Medisch Centrum Utrecht

Address

Heidelberglaan 100

City

Utrecht

Postcode

3584 CX

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

DHS Onderzoeksbureau

Public contact point

Organisation

Universitair Medisch Centrum Utrecht

Contact name

DHS Onderzoeksbureau

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Summary of results Art. 37(4) CTR

Documents 5 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