Study on efficacy of nintedanib for treatment of epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients - EPISTOP

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospices Civils De Lyon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

16 Jun 2025 → ongoing

Decision date (initial)

2025-05-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

CHUV Lausanne university hospital · Boehringher Ingelheim

External identifiers

EU CT number

2024-518886-89-00

ClinicalTrials.gov

NCT04976036

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Whether the proportion of HHT patients with a reduction of at least 30% of epistaxis duration after 16 weeks of study treatment compared to baseline, is significantly higher in patients treated with nintedanib than in patients treated with placebo.

Secondary objectives 2

1. To assess the change under experimental treatment in epistaxis severity scores, quality of life, and biological values linked to anemia in HHT patients. The same objectives will also be assessed two months after follow-up to investigate a possible long term effect of experimental treatment.
2. Assess long-term safety of nintedanib and its tolerability in terms of bleeding risks, and incidence of gastro-intestinal, hepato-biliary and renal side effects in HHT patients.

Conditions and MedDRA coding

Hereditary haemorrhagic telangiectasia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Signed informed consent
2. Definite HHT disease (defined as the presence of a pathogenic mutation in one of the HHT genes, or the presence of 3 out of 4 Curaçao clinical criteria2 )
3. Aged ≥18 years at the time of informed consent
4. Moderate to serious epistaxis (Epistaxis Severity Score ESS≥2.5)
5. Absence of cerebral arteriovenous malformation demonstrated by brain imaging

Exclusion criteria 20

1. Women who are pregnant or breastfeeding because of the potential dangerous effect of the treatment on the fetus or infant
2. Coronary heart disease
3. Thrombotic event within the last 12 months
4. Long QT syndrome (on ECG performed at screening)
5. Known allergy to Nintenanib, soya, peanuts
6. Bevacizumab, pazopanib or other anti-angiogenic treatments within the last 12 months
7. Concomitant treatment with ketoconazole, erythromycin, rifampicin, carbamazepine, phenytoin, St John’s Wort
8. Surgery within the last 3 months or planned within the next 9 months
9. Recent unhealed wound
10. Any other serious underlying medical condition that could interfere with study treatment and potential adverse events
11. Any mental or other impairment that may compromise compliance with the study requirements.
12. Pregnant woman or woman of child bearing potential not using two effective methods of birth control (one barrier and one highly effective non-barrier) for at least 1 month prior to trial and/or committing to using it until 3 months after the end of treatment.
13. Acute infection
14. AST or ALT or ALKP or GGT or total bilirubin >1.5x (or >2.5x in patients known for Gilbert’s syndrome) the upper limit of normal
15. Renal clearance by Cockcroft-Gault formula <30 ml/min
16. Untreated pulmonary arteriovenous malformation
17. Hemoptysis or hematuria within the last 12 months
18. Ulcus or active gastric bleeding within the last 12 months
19. Anticoagulant or antiplatelets treatment
20. Participation in another interventional clinical trial which may interfere with the proposal trial (judgment of the investigator)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Proportion of patients with at least 30% reduction of monthly epistaxis duration after 16 weeks of study treatment (at V6, week 24) compared to baseline (V1, week 8) assessed in nintedanib arm and in placebo arm.
2. The monthly epistaxis duration after 16 weeks of study treatment is defined as the average of epistaxis duration during the last 12 weeks of study treatment (minutes/4-weeks period averaged for weeks 12 to 24, i.e. V3 to V6)
3. The monthly epistaxis duration at baseline is defined as the average of epistaxis duration during the observation period (minutes/4-weeks period averaged for weeks 0 to 8, i.e. V0 to V1).

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation

Hospices Civils De Lyon

Address

3 Quai Des Celestins, Bp 2251 Bp 2251

City

Lyon Cedex 02

Postcode

69229

Country

France

Scientific contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr DUPUIS GIROD

Public contact point

Organisation

Hospices Civils De Lyon

Contact name

Dr DUPUIS GIROD

Locations

1 EU/EEA country · 2 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