Patient reported efficacy of intranasal lysine-aspirin in controlling NSAID-exacerbated respiratory disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients, Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Otorhinolaryngologic Diseases [C09]

Trial duration

15 Nov 2022 → 11 Mar 2026

Decision date (initial)

2024-10-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

The Research Foundation – Flanders (FWO)

External identifiers

EU CT number

2024-517437-40-00

EudraCT number

2022-001611-50

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

1) Effect of nasal ATAD with lysine-aspirin on patient reported outcomes:
o Rhinosinusitis and Asthma severity Visual analogue scale (VAS)
o Nasal Congestion/Obstruction (NC) score
o Short version of the Olfactory Disorders-Negative Statements (sQODNS)
o Asthma control, measured with the Asthma Control Questionnaire (ACQ-6);
o Health-related quality of life, using disease-specific health-related quality of life score, such as the Sino-Nasal Outcome Test-22 (SNOT-22) and the Standardised Asthma Quality of Life Questionnaire (AQLQ (S));
o Patient recognition of improvement: Patient Global Impression of Change (PGIC).
o EQ-5D-5L to describe and value health
2) Incidence of significant serious and non-serious adverse events related to gastro- intestinal disturbance (nausea, vomiting, diarrhoea, abdominal pain).
3) Effect of nasal ATAD on provoking dose during nasal lysine-aspirin provocation test

Secondary objectives 3

1. Effect of nasal lysine-aspirin on upper and lower airway
2. Effect of nasal lysine-aspirin on polyp growth
3. Effect of nasal lysine-aspirin on corticosteroid use

Conditions and MedDRA coding

Nonsteroidal anti-inflammatory drug Exacerbated Respiratory Disease (N-ERD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Use of highly effective methods of birth control; defined as those that, alone or in combination, result in low failure rate (i.e., less than 1% per year) when used consistently and correctly; such as implants, injectables, combined oral contraceptives, some IUDs, true sexual abstinence (i.e. refraining from heterosexual intercourse during the entire period of risk associated with the Trial treatment(s)) or commitment to a vasectomised partner
3. Patient has N-ERD: intolerance to aspirin is confirmed by a nasal lysine-aspirin provocation test in the pre-trial S65796
4. Patients older than 18 years
5. Patient is using mometasone furoate or fluticasone propionate on a dose regimen of 2 actuations in each nostril once daily for at least 2 weeks before the screening visit

Exclusion criteria 13

1. Any disorder, which in the Investigator’s opinion might jeopardise the participant’s safety or compliance with the protocol
2. Any prior or concomitant treatment(s) that might jeopardise the participant’s safety or that would compromise the integrity of the Trial
3. Female who is pregnant or breast-feeding
4. Participation in an interventional Trial with an investigational medicinal product (IMP) or device
5. Participants with severe gastro-intestinal disease or with bleeding diathesis
6. Participants with chronic urticaria
7. Participants with unstable cardiovascular conditions/cardiopulmonary disease where epinephrine is contraindicated
8. Participants with severe chronic obstructive pulmonary disease (COPD)
9. Participants with poorly controlled asthma defined as: a) FEV1 < 65 % predicted (before the start of the study treatment) while on preventative inhalers, or b) Participants who experienced an asthma exacerbation requiring hospitalization (>24 hours) for treatment of asthma within 3 months before screening
10. Participants who have undergone any intranasal and/or sinus surgery (including polypectomy) within 2 months before screening
11. Participants with major anatomical nasal abnormalities or conditions/concomitant diseases being responsible for nasal obstruction and making them nonevaluable at screening, but not limited to: antrochoanal polyps, nasal septal deviation that would occlude at least one nostril, acute sinusitis, nasal infection or upper respiratory infection requiring treament with systemic antibiotics, antivirals or antifungals, ongoing rhinitis medicamentosa, fungal rhinosinusitis
12. Participants who have taken biologic therapy within 3 months prior to screening or 5 half-lives, whichever is longer
13. Participants not willing to respect the requirements as defined in section 5.3 ‘Concomitant/Prohibited Medication/Treatment’

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 10

1. Change from baseline in VAS for rhinosinusitis and asthma severity
2. Change from baseline in NC score
3. Change from baseline in ACQ-6 score
4. Change from baseline in SNOT-22 score
5. Change from baseline in AQLQ(S)
6. Change from baseline in PGIC
7. Change from baseline in sQODNS score
8. Change from baseline in EQ-5D-5L
9. Change from baseline in provoking dose
10. Proportion of patients with serious and non-serious adverse events related to gastro-intestinal disturbance (nausea, vomiting, diarrhoea, abdominal pain)

Secondary endpoints 8

1. Change from baseline in PNIF
2. Change from baseline in smell score (UPSIT)
3. Change from baseline in FEV1
4. Change from baseline in FeNO and nNO
5. Change from baseline in NPS
6. Proportion of patients who have or are planned for surgery of nasal polyps, as well as time-to-event
7. Proportion of patients with OCS use for chronic rhinosinusitis/asthma exacerbation, as well as time to first course, number of courses, total dose used, total duration
8. Dosage (dose and frequency) of inhaled/intranasal corticosteroids, reported as dosage during desensitisation and dosage during maintenance therapy (after goal of escalation is reached)

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Peter Hellings

Public contact point

Organisation

UZ Leuven

Contact name

Peter Hellings

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

Layperson summary Annex V

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