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Immunomodulatory Treatment of Interstitial Lung Disease Associated With Surfactant Related Gene Variants
Sponsor: Assistance Publique - Hôpitaux de Paris
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. tolerance of the triple therapy, 2. correlation between the respiratory, radiological and clinical functional response, 3. quality of life of the patients, 4. overall survival, transplant-free survival, exacerbation free-survival, hospitalization-free survival Secondary endpoints: 1. 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) 2. Thoracic CT scan and PFT at 6 months and one year after randomization 3. Quality of life questionnaire (EORTC QLQ-C30, v3.0) at 3 months, 6 months, 9 months and one year after randomization, 4. 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. Design of the study : Multicenter, randomized, controlled, two-arm, parallel, open-label superiority study comparing triple immunomodulatory therapy (prednisone, azithromycin, and hydroxychloroquine) to standard of care Category : Category 2 Population of study participants: Patients aged over 18 years with ILD and SRG variant Number of participants included : 30 Design of the study : Multicenter, randomized, controlled, two-arm, parallel, open-label superiority study comparing triple immunomodulatory therapy (prednisone, azithromycin, and hydroxychloroquine) to standard of care.
Key Details
Gender
All
Age Range
18 Years - 80 Years
Study Type
INTERVENTIONAL
Enrollment
30
Start Date
2026-10-01
Completion Date
2027-10-01
Last Updated
2026-03-02
Healthy Volunteers
No
Conditions
Interventions
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
Prednisone 10 mg/day
Route of administration: oral route Duration of treatment: 12 months Market authorization: yes Use in their market authorization indication: no
Hydroxychloroquine 400 mg/day
Route of administration: oral route Duration of treatment: 12 months Market authorization: yes Use in their market authorization indication: no
Active Comparator: Standard of care
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.