Efficacy of methylprednisolone pulses in neuroendocrine cells hyperplasia of infancy: an early phase study (CORTICONEHI).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

30 Jun 2025 → ongoing

Decision date (initial)

2024-06-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AP-HP · Ministry of Health, 2022 national PHRC program

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To evaluate the efficacy on oxygen therapy need of a 6 months methylprednisolone pulses in NEHI patients at M18

Secondary objectives 8

1. To evaluate the number of patients requiring continuous oxygen therapy (meaning sleep and awake oxygen therapy by opposition to sleep oxygen only) over time
2. To evaluate the number of patients requiring only sleep oxygen over time
3. To evaluate the number of patients with a normal respiratory rate
4. To evaluate ChILD healing (reduction of severity) over time
5. To evaluate Parents and patient’s QoL
6. To evaluate impact of NEHI on feeding and growth status
7. Exploratory objective, to compare the family impact PedsQL questionnaire to the newly described chILD-PQoL questionnaire
8. Exploratory objective, to study thoracic CT-scan evolution

Conditions and MedDRA coding

NEUROENDOCRINE CELLS HYPERPLASIA OF INFANCY

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Infant aged under 12 months
2. NEHI diagnosis based on: - The recently validated clinical Liptzin score ≥7/10 associated with a suggestive thoracic CT pattern with ground glass opacities confined to middle lobe, lingula, and paramediastinal lung areas OR - a clinical and thoracic CT suspicion and a lung biopsy showing an increased number of neuroendocrine cells in the epithelial airways area (at least one bronchiole with at least 10% of neuroendocrine cells)
3. Oxygen requirement (awake and/or asleep) based on the usual pediatric recommendations
4. Followed in one of the RespiRare participating centers
5. Written informed consent of the holder(s) of its legal representative at the inclusion

Exclusion criteria 9

1. Other cause of chILD assessed by lab biology tests, genetic analysis for surfactant genes (if available), bronchoalveolar lavage, and/or lung biopsy
2. Patient treated with IV methylprednisolone pulses before (any time)
3. Diabetes
4. Uncontrolled arterial hypertension
5. Absence of Health care insurance
6. Ongoing infection
7. Immunization with a live attenuated vaccine within the past two weeks
8. Long term treatment with Azithromycin and/or Hydroxychloroquine
9. Patients already included in an interventional study (RIPH1, clinical investigation or clinical trial)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of children still requiring oxygen therapy at M18 (i.e. 18 months after the inclusion)

Secondary endpoints 11

1. Efficacy endpoint, number of children requiring only sleep oxygen at M18.
2. Efficacy endpoint, number of children with a normal respiratory rate at rest at M18
3. Efficacy endpoint, difference of Fan’s severity score assessing the severity of children with ILD (respiratory symptoms, SpO2<90% at sleep or exertion, SpO2<90% at rest and pulmonary hypertension) between M0) and M18
4. Efficacy endpoint, patients and family impact PedsQL and the chILD QoL scores; the chILDPQoL score, a parents QoL score (submitted for publication) at M0 and M18
5. Efficacy endpoint, number of patients requiring at least one enteral nutrition episode (based on the physician appreciation in case of abnormal weight curve) between M0 and M18
6. Safety endpoint, number of unexpected hospitalizations for a respiratory exacerbation between M0 and M18
7. Safety endpoint, number of antibiotic courses for an infectious lung exacerbation between M0 and M18
8. Safety endpoint, at M6, the number of patients with at least once systolic or diastolic arterial blood pressure (AP) over 2SD for the age at the days of methylprednisolone pulses
9. Safety endpoints, the number of patients with at least one an elevated fasting glycaemia before the first day of methylprednisolone pulses
10. Exploratory endpoint, correlation between family impact PedsQL questionnaire and the newly described chILD-PQoL questionnaire at each time of measurement
11. Exploratory endpoint, number of patients with an extension, a stability, a decrease or an absence of the GGO lesions on the CT-scan at M6 and M18

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nadia NATHAN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Nadia NATHAN

Locations

1 EU/EEA country · 27 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 22 files

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

Application history

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