Immunomodulatory Treatment of Interstitial Lung Disease Associated With Surfactant Related Gene Variants

NCT07443436 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP251230
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

Scientific justification : Variants in surfactant-related genes (SRG) explain approximately 6% of familial pulmonary fibrosis (FPF). The pathophysiology is unknown and seems to involve endoplasmic reticulum stress in type 2 alveolar epithelial cells. Variable improvement in the prognosis of childhood and adult interstitial lung disease (ILD) associated with a variant of a SRG, initially reported to be lethal within months of diagnosis, has been observed since the consensual use of prednisone, azithromycin and hydroxychloroquine targeting endoplasmic reticulum stress, without demonstration of the efficacy of any of these treatments alone or in combination. The investigators hypothesize that a treatment combining prednisone, azithromycin and hydroxychloroquine is safe and could improve the prognosis of adult patients with ILD associated with SRG variant. Main objective and primary endpoint : Main objective: Evaluate the efficacy of triple immunomodulatory therapy (prednisone, azithromycin and hydroxychloroquine) for 12 months in patients with ILD associated with a variant of a surfactant-related gene. Primary endpoint: Difference in forced vital capacity decline between the 2 groups at one year. Secondary objectives and endpoints : Secondary objectives:

1. 1.tolerance of the triple therapy,
2. 2.correlation between the respiratory, radiological and clinical functional response,
3. 3.quality of life of the patients,
4. 4.overall survival, transplant-free survival, exacerbation free-survival, hospitalization-free survival
5. 5.Clinical and biological tolerance (occurrence of an adverse effect during treatment), ECG (at 3, 6, 9, 12 months after randomization) (only HCQ or AZI patients) and ophthalmological (at one year after randomization)
6. 6.Thoracic CT scan and PFT at 6 months and one year after randomization
7. 7.Quality of life questionnaire (EORTC QLQ-C30, v3.0) at 3 months, 6 months, 9 months and one year after randomization,
8. 8.Collection of vital status, lung transplantation, hospitalization for pulmonary and non-pulmonary causes and episodes of exacerbation at each visit until the end of follow-up 12 months after randomization.

Conditions

Interstitial Lung Disease

Outcome Measures

Primary Outcomes (1)

• Difference in forced vital capacity decline between the 2 groups at one year.

  Evaluate the efficacy of triple immunomodulatory therapy (prednisone, azithromycin and hydroxychloroquine) for 12 months in patients with ILD associated with a variant of a surfactant-related gene.

  12 Months

Secondary Outcomes (22)

• tolerance of the triple therapy

  12 months

• correlation between the respiratory, radiological and clinical functional response,

  12 months

• Quality of life of the patients

  12 months

• tolerance of the triple therapy

  6 months

• tolerance of the triple therapy

  3 months

Study Arms (2)

Prednisone 10 mg/day -Hydroxychloroquine 400 mg/day - Azithromycin 250mg*3

EXPERIMENTAL

The experimental treatment will be the combination of: * Prednisone 10 mg/day (1 tablet/day) * Hydroxychloroquine 400 mg/day (2 tablets/day) * Azithromycin 250 mg x3/week (3 tablets/week) Route of administration: oral route Duration of treatment: 12 months Market authorization: yes Use in their market authorization indication: no

Drug: Azithromycin 250 mg x3/week (3 tablets/week); Drug: Prednisone 10 mg/day; Drug: Hydroxychloroquine 400 mg/day

Standard of care

ACTIVE COMPARATOR

Standard of care: any symptomatic treatment to interstitial lung disease. No other experimental or off-label treatment (such as ivacaftor) will be allowed during the study.

Drug: Active Comparator: Standard of care

Interventions

Azithromycin 250 mg x3/week (3 tablets/week) DRUG

Route of administration: oral route Duration of treatment: 12 months Market authorization: yes Use in their market authorization indication: no

Prednisone 10 mg/day -Hydroxychloroquine 400 mg/day - Azithromycin 250mg*3

Prednisone 10 mg/day DRUG

Route of administration: oral route Duration of treatment: 12 months Market authorization: yes Use in their market authorization indication: no

Prednisone 10 mg/day -Hydroxychloroquine 400 mg/day - Azithromycin 250mg*3

Hydroxychloroquine 400 mg/day DRUG

Route of administration: oral route Duration of treatment: 12 months Market authorization: yes Use in their market authorization indication: no

Prednisone 10 mg/day -Hydroxychloroquine 400 mg/day - Azithromycin 250mg*3

Active Comparator: Standard of care DRUG

Standard of care: any symptomatic treatment to interstitial lung disease. No other experimental or off-label treatment (such as ivacaftor) will be allowed during the study.

Standard of care

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and \<80 years
• Carrier of a variant classified as pathogenic or probably pathogenic or considered as eligible by the genetic multidisciplinary discussion in SFTPA1, SFTPA2, SFTPC, NKX2-1, SFTPB or two variants classified as pathogenic or probably pathogenic or considered as eligible by the genetic multidisciplinary discussion in ABCA3 or SFTPB
• ILD whatever the pattern corresponding to a volume \> 10% of the total lung on a CT scan of less than 2 years

You may not qualify if:

• Contraindication to azithromycin and hydroxychloroquine and prednisone
• Pregnancy and breastfeeding
• Enrolment to another interventional study (clinical trial on medicinal product, medical device and interventional research involving human participants not concerning health product)
• Subject deprived of liberty or subject under legal protection measure
• No affiliation to any health insurance system
• Refusal to participate to the study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Azithromycin; Prednisone; Hydroxychloroquine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Annabelle METOIS

CONTACT

0140257939; annabelle/metois@aphp.fr

BORIE Raphaël

CONTACT

raphael.borie@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2026
• First Posted: March 2, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: March 2, 2026

Record last verified: 2026-01