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NCT Number: NCT07443436

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

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.

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Key information

Conditions

Interstitial Lung Disease Lung Diseases Lung Diseases, Interstitial Respiratory Tract Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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

Drug

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

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

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.

Primary outcomes

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

    Time frame: 12 Months

    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.

Secondary outcomes

  1. tolerance of the triple therapy

    Time frame: 12 months

    Clinical and biological tolerance (occurrence of an adverse effect during treatment), ECG (including QTc prolongation) (at 3, 6, 9, 12 months after randomization) (only HCQ or AZI patients) and ophthalmological (at one year after randomization)

  2. correlation between the respiratory, radiological and clinical functional response,

    Time frame: 12 months

    Thoracic CT scan (progression criteria [99]) and PFT (Pulmonary function tests) at one year after randomization

  3. Quality of life of the patients

    Time frame: 12 months

    Quality of life questionnaire (SF-36, scale from 0 to 100, where 0 represents the poorest health and 100 represents the best possible health) (EORTC QLQ-C30, v3.0 : a validated patient-reported questionnaire for assessing quality of life in cancer patients.) at one year after randomization,

  4. tolerance of the triple therapy

    Time frame: 6 months

    Clinical and biological tolerance (occurrence of an adverse effect during treatment), ECG (including QTc prolongation) at 6, months after randomization (only HCQ or AZI patients) and ophthalmological (at one year after randomization)

  5. tolerance of the triple therapy

    Time frame: 3 months

    Clinical and biological tolerance (occurrence of an adverse effect during treatment), ECG (including QTc prolongation) at 3 months after randomization (only HCQ or AZI patients) and ophthalmological (at one year after randomization)

  6. correlation between the respiratory, radiological and clinical functional response,

    Time frame: 6 months

    Thoracic CT scan (progression criteria [99]) and PFT (Pulmonary function tests) at 6 months after randomization

  7. Quality of life of the patients

    Time frame: 9 months

    Quality of life questionnaire (SF-36,scale from 0 to 100, where 0 represents the poorest health and 100 represents the best possible health) (EORTC QLQ-C30, v3.0 : a validated patient-reported questionnaire for assessing quality of life in cancer patients.) at 9 months after randomization,

  8. Quality of life of the patients

    Time frame: 6 months

    Quality of life questionnaire (SF-36 scale from 0 to 100, where 0 represents the poorest health and 100 represents the best possible health) (EORTC QLQ-C30, v3.0 :a validated patient-reported questionnaire for assessing quality of life in cancer patients. ) at 6 months after randomization,

  9. Quality of life of the patients

    Time frame: 3 months

    Quality of life questionnaire (SF-36, scale from 0 to 100, where 0 represents the poorest health and 100 represents the best possible health) (EORTC QLQ-C30, v3.0 :a validated patient-reported questionnaire for assessing quality of life in cancer patients ) at 3 months after randomization,

  10. Overall survival

    Time frame: 12 months

    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

  11. Transplant-free survival

    Time frame: 12 months

    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

  12. Exacerbation free-survival

    Time frame: 12 months

    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

  13. Hospitalization-free survival

    Time frame: 12 months

    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

  14. tolerance of the triple therapy

    Time frame: 9 months

    Clinical and biological tolerance (occurrence of an adverse effect during treatment),

  15. tolerance of the triple therapy

    Time frame: 12 months

    ECG (including QTc prolongation) at 12 months after randomization (only HCQ or AZI patients)

  16. tolerance of the triple therapy

    Time frame: 12 months

    Ophthalmological (at one year after randomization)

  17. tolerance of the triple therapy

    Time frame: 9 months

    ECG (including QTc prolongation) at , 9 months after randomization (only HCQ or AZI patients)

  18. tolerance of the triple therapy

    Time frame: 6 months

    ECG (including QTc prolongation) at 6 months after randomization (only HCQ or AZI patients)

  19. tolerance of the triple therapy

    Time frame: 3 months

    ECG (including QTc prolongation) at 3 months after randomization (only HCQ or AZI patients)

  20. Overall survival

    Time frame: 9 months

    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 9 months after randomization

  21. Overall survival

    Time frame: 6 months

    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 6 months after randomization

  22. Overall survival

    Time frame: 3 months

    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 3 months after randomization

Study contacts

Contact information is provided by the study sponsor or research team.

Annabelle METOIS

CONTACT

annabelle/[email protected]

0140257939

BORIE Raphaël

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Acronym: TIPS

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Mar 2, 2026
Registry last updated
Mar 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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