A Study to Find Out How Nerandomilast is Tolerated, Handled by the Body, and if it Helps Children and Adolescents With Interstitial Lung Disease (FIBRONEER-chILD)

Official title

A Study to Evaluate the Dose-exposure, Safety, and Exploratory Efficacy of Nerandomilast in Children and Adolescents From 2 Years to Less Than 18 Years of Age With Fibrosing Interstitial Lung Disease (Part A: Double-blind, Placebo-controlled in Children From 6 to Less Than 18 Years of Age and Open-label Active Treatment in Children From 2 to Less Than 6 Years of Age), Followed by an Open-label Phase With Active Treatment (Part B)

Overview

This study is open to children and adolescents aged 2 to 17 years with interstitial lung disease (ILD). Nerandomilast has just been approved in some countries to help adults with a lung condition called idiopathic pulmonary fibrosis. The purpose of this study is to understand how nerandomilast is tolerated and handled by the body and whether nerandomilast also helps children and adolescents with ILD. For participants aged 6 to 17 years when joining, the study has 2 parts. In the first part, participants are put into 1 of 2 groups randomly, which means by chance. One group gets nerandomilast and the other group placebo. Placebo looks like nerandomilast but does not contain any medicine. Participants are twice as likely to be in the nerandomilast group. They take tablets twice a day for 6 months. After these 6 months, in the second part of this study, they get nerandomilast for at least 2 years regardless of what they got in the first part. Young participants aged 2 to 5 years when joining get nerandomilast from the start. They receive tablets twice a day for at least 2 and a half years. Depending on when a person joins, the study lasts between 2 and a half years and up to 5 years. During this time, participants may visit the study site about 18 to 30 times. Study doctors collect blood samples to check participants' health and to find out how their body handles the study medicine. Doctors also check the function of the lungs, body growth, and how participants feel. The study doctors also regularly check participants' health and take note of any changes. For participants aged 6 to 17 years, the results are compared between the groups to see whether nerandomilast treatment helps children and adolescents.

Interventions

• Drug Nerandomilast
  Nerandomilast
• Drug Placebo
  Placebo

Primary outcome measures

• Area under the concentration curve (AUC) T,SS based on sampling at steady state using rich sampling in participants from 6 years to less than 18 years and sparse sampling in participants younger than 6 years [Time frame: At week 2 in Part A and Week 28 in Part B]
• Occurrence of a treatment-emergent adverse event [Time frame: up to Week 26]

Secondary outcome measures (11)

• Absolute change from baseline in oxygen saturation (SpO2) [%] on room air at rest [Time frame: at Week 26 and Week 52]
• Absolute change from baseline in height [cm] [Time frame: at Week 26 and Week 52]
• Absolute change from baseline in pediatric quality of life inventory (PedsQL™) [Time frame: at Week 26 and Week 52]
• Occurrence of a treatment-emergent adverse event (Yes/No) over the whole trial [Time frame: up to 5 years]
• Time to first respiratory-related hospitalisation [days] over the whole trial [Time frame: up to 5 years]
• Time to first acute interstitial lung disease (ILD) exacerbation or death [days] over the whole trial [Time frame: up to 5 years]
• Time to death [days] over the whole trial [Time frame: up to 5 years]
• Acceptability based on number/size of tablets [Time frame: at Week 2 and Week 26]
• Acceptability based on the use of the dispenser [Time frame: at Week 2 and Week 26]
• Absolute change from baseline in FVC [% predicted] (applicable to participants ≥6 years) [Time frame: at Week 26 and Week 52]
• Absolute change from baseline in 6-min walk distance [m] (applicable to participants ≥6 years) [Time frame: at Week 26 and Week 52]

Eligibility criteria

Inclusion criteria

• Children and adolescents 2 to <18 years old at Visit 2.
• Participants with evidence of fibrosing ILD on high-resolution computed tomography (HRCT) within 12 months of Visit 1 as assessed by the investigator and confirmed by central review.
• For children ≥6 years: Participants with forced vital capacity (FVC) % predicted ≥25% at Visit 2.
• Participants with clinically significant fibrosing ILD at Visit 2, as assessed by the investigator based on any of the following:

• Fan score ≥3, or
• Documented evidence of clinical progression over time based on either

• a 5-10% relative decline in FVC % predicted accompanied by worsening symptoms, or
• a ≥10% relative decline in FVC % predicted, or
• increased fibrosis on HRCT, or
• other measures of clinical worsening attributed to progressive lung disease (e.g. increased oxygen requirement, decreased diffusion capacity).

Further inclusion criteria apply.

Exclusion criteria

• Previous treatment with nerandomilast.
• Participants treated with other oral/systemic PDE4 and non-selective PDE inhibitors within 30 days before Visit 1.
• Participants treated with pirfenidone in the 8 weeks prior to Visit 1.
• Unstable pulmonary arterial hypertension (PAH).
• Active vasculitis, unstable or uncontrolled within 8 weeks prior to Visit 1 or during the screening period.
• Any suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour) in the past (lifetime).
• Any suicidal ideation of type 4 or 5 on the columbia suicidal severity rating scale (C-SSRS) in the past 3 months at Visit 1 or at Visit 2 (i.e. active suicidal thought with method and intent but without specific plan; or active suicidal thought with method, intent, and plan).
• Participants with clinically significant depression symptoms defined as the short version of mood and feeling questionnaire (SMFQ) score ≥8.

Further exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 7 centers

• Children's Hospital Los Angeles — Los Angeles
• Children's Hospital Colorado — Aurora
• Johns Hopkins Hospital — Baltimore
• Boston Children's Hospital — Boston
• University of Minnesota — Minneapolis
• Nationwide Children's Hospital — Columbus
• Children's Hospital of Philadelphia — Philadelphia

France · 5 centers

• HOP Femme Mère Enfant — Bron
• HOP Intercommunal — Créteil
• HOP Timone — Marseille
• HOP Armand-Trousseau — Paris
• HOP Necker - Enfants Malades — Paris

Brazil · 4 centers

• Serviços Medicos Respirar Sul Fluminense — Barra Mansa
• Associação dos Funcionários Públicos do Estado do Rio Grande do Sul - Hospital Ernesto Dor — Porto Alegre
• IMIP Pernambuco — Recife
• Centro de Pesquisa Clinica do Instituto da Crianca - HCFMUSP — São Paulo

China · 3 centers

• Beijing Children's Hospital, Capital Medical University — Beijing
• Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal Universi — Changsha
• The Children's Hospital of Fudan University — Shanghai

Germany · 3 centers

• Charité - Universitätsmedizin Berlin — Berlin
• Hamburger Zentrum für Kinder- und Jugendrheumatologie — Hamburg
• Medizinische Hochschule Hannover — Hanover

Japan · 3 centers

• Fukuoka Children's Hospital — Fukuoka, Fukuoka
• Osaka Women's and Children's Hospital — Osaka, Izumi
• National Center for Child Health and Development — Tokyo, Setagaya-ku

Argentina · 2 centers

• Fundacion Respirar — CABA
• Hospital de Pediatria Prof. Dr. Juan P. Garrahan — CABA

Canada · 2 centers

• Alberta Children's Hospital — Calgary
• The Hospital for Sick Children — Toronto

Finland · 2 centers

• HUS Lasten ja nuorten sairaudet, Kliinisen tutkimuksen yksikkö — Helsinki
• Tampere University Hospital — Tampere

Italy · 2 centers

• Istituto G. Gaslini — Genova
• Ospedale Pediatrico Bambino Gesù — Roma

Mexico · 2 centers

• Centro de Investigacion Clinica y Medicina Traslacional (CIMeT) — Guadalajara
• Clinical Research Institute S.C. — Tlalnepantla

Spain · 2 centers

• Hospital Universitari Vall d'Hebron — Barcelona
• Hospital Virgen del Rocío — Seville

United Kingdom · 2 centers

• Birmingham Children's Hospital — Birmingham
• King's College Hospital — London

Australia · 1 center

• Women's and Children's Hospital — North Adelaide

Belgium · 1 center

• Brussels - UNIV HUDERF — Brussels

Czechia · 1 center

• University Hospital Motol — Prague

Denmark · 1 center

• Aarhus University Hospital — Aarhus N

Greece · 1 center

• Aristotle University, Thessaloniki — Thessaloniki

Netherlands · 1 center

• Amsterdam University Medical Center — Amsterdam

Poland · 1 center

• University Clinical Center of the Medical University of Warsaw — Warsaw

Portugal · 1 center

• ULS de Santa Maria, E.P.E — Lisbon

South Korea · 1 center

• Seoul National University Hospital — Seoul

Identifiers

NCT: NCT07366034 · 1305-0022 · 2025-523369-32-00 · 1111-1326-6351

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗