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Not yet recruitingNCT07210008RUBYUpdated Oct 7, 2025

"Randomized Controlled Trial Testing the Efficacy of Corticosteroid Therapy Versus Placebo in Fibrotic Hypersensitivity Pneumonitis"

A Phase 3 interventional study of Prednisolone and Placebo in Hypersensitivity Pneumonitis, sponsored by Assistance Publique - Hôpitaux de Paris. Not yet recruiting. Open to participants aged 18 Years to 90 Years. Per ClinicalTrials.gov, last updated 2025-10-07.

Sponsored by Assistance Publique - Hôpitaux de Paris · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years to 90 Years
Sex
All
01

Study summary

Hypersensitivity Pneumonitis (HP) is an immune-mediated disease that manifests as interstitial lung disease after exposure to an inhaled antigen, often unidentified. HP can be classified as non-fibrotic or fibrotic HP. Fibrotic HP is associated with impaired quality of life (QoL) and reduced survival. The value and decline of forced vital capacity (FVC) are predictive factors of mortality in fibrotic HP. In most expert centres worldwide, corticosteroids are chosen as the first-line drug to treat fibrotic HP in clinical practice. However, this strategy has not been validated in a randomized controlled trial and it remains controversial, Moreover, corticosteroids are responsible for potentially serious adverse events. The hypothesis is that prednisolone, as a first-line treatment in fibrotic hypersensitivity pneumonitis (HP), slows down FVC decline compared to placebo.

The main objective is to assess the efficacy of first-line treatment with prednisolone against placebo, on the 6-month change in FVC in percent of predicted value (% pred).The primary endpoint will be the absolute change in FVC (% pred) from baseline (inclusion visit,M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.

Read the detailed description

Hypersensitivity Pneumonitis (HP) is an immune-mediated disease that manifests as interstitial lung disease after exposure to an inhaled antigen, often unidentified. HP can be classified as non-fibrotic or fibrotic HP. Fibrotic HP is associated with impaired quality of life (QoL) and reduced survival. The value and decline of forced vital capacity (FVC) are predictive factors of mortality in fibrotic HP. In most expert centres worldwide, corticosteroids are chosen as the first-line drug to treat fibrotic HP in clinical practice. However, this strategy has not been validated in a randomized controlled trial and it remains controversial, Moreover, corticosteroids are responsible for potentially serious adverse events. The hypothesis is that prednisolone, as a first-line treatment in fibrotic hypersensitivity pneumonitis (HP), slows down FVC decline compared to placebo.

The main objective is to assess the efficacy of first-line treatment with prednisolone against placebo, on the 6-month change in FVC in percent of predicted value (% pred).The primary endpoint will be the absolute change in FVC (% pred) from baseline (inclusion visit,M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.

RUBY, is a national multicenter, randomized, double blind, placebo-controlled, superiority trial comparing the efficacy of prednisolone to placebo on the change in FVC (% pred) at 6 months.

The investigators will randomly assign participants (1:1 ratio, stratification according to the identification of an inciting antigen) to receive oral prednisolone or placebo for a period of 6 months with a follow-up of 12 months. The primary endpoint will be assessed at Month 6.

The investigators plan to include 120 participants.

02

Conditions studied

  • Hypersensitivity Pneumonitis
03

Who can participate

Ages eligible
18 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patient aged above 18 years and under 90 years old
  • Diagnosis of fibrotic HP ("definite" or "high confidence") after MDD according to the criteria proposed by guidelines [5]
  • Fibrosis extent ≥ 10% on chest HRCT
  • Mild to moderate functional impairment defined by FVC ≥ 50% pred and DLco ≥ 30% pred
  • Written informed consent for participation in study
  • Patient affiliated to a social security scheme or CMU beneficiary
  • Effective contraception for men and woman of childbearing age.

Exclusion criteria

Exclusion Criteria:

  • Uncertain diagnosis of fibrotic HP ("low confidence" or "unlikely") after MDD according to the criteria proposed by guidelines [5].
  • Severe functional impairment defined by FVC \< 50% pred and DLco \< 30% pred.
  • Patient previously treated or currently being treated for fibrotic HP (with corticosteroids, any immunosuppressive agent, or anti- fibrotic therapies).
  • Person under guardianship/ curatorship (sous tutelle/curatelle)
  • Contraindication to corticosteroid therapy (hypersensitivity to the active substances or to one of the excipients, severe infections, psychotic states not controlled by treatment, live vaccines, uncontrolled diabetes mellitus and uncontrolled arterial hypertension.) or to auxiliary medicinal products
  • Patient deprived of liberty under judicial or administrative decision
  • Patient participating in another clinical trial with an investigational medicinal product. The patient may participate in another clinical trial after the 6 months of treatment in this study
  • Pregnancy or breastfeeding woman
  • Patient receiving AME (state medical assistance)
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Prednisolone (oral)

    Prednisolone (oral) will be administered and tapered over 6 months, according to the schedule detailed in the protocol(Cumulative dose: 2430mg/ 6months). Active Comparator: prednisolone. Oral prednisolone will be administered and tapered over 6 months, according to the following schedule: 0.5 mg/kg/day (not exceeding 40mg/day) x 4 weeks, 0.25 mg/kg/day (not exceeding 20mg/day) x 4 weeks, 15 mg/day x 4 weeks, 10 mg/days x 4 weeks, 5 mg/day x 10 weeks

    Drug: Prednisolone

  • Placebo comparator
    Placebo

    Dispersible placebo administered and tapered over 6 months according to the schedule detailed in the protocol

    Drug: Placebo

Interventions

  • DrugPrednisolone

    Active Comparator: prednisolone. Oral prednisolone will be administered and tapered over 6 months, according to the following schedule\*: 0.5 mg/kg/day (not exceeding 40mg/day) x 4 weeks, 0.25 mg/kg/day (not exceeding 20mg/day) x 4 weeks, 15 mg/day x 4 weeks, 10 mg/days x 4 weeks, 5 mg/day x 10 weeks

  • DrugPlacebo

    Dispersible placebo administered and tapered over 6 months according to the schedule detailed in the protocol

05

What researchers measure

Primary outcomes

  1. Absolute change in FVC (% pred)

    Absolute change in FVC (% pred) from baseline (inclusion visit, M0) to 6 months (M6) will be compared between the placebo arm and the prednisolone arm.

    Time frame: at month 6

Secondary outcomes

  1. Absolute change in FVC (% pred) according to the presence of a causal antigen at Month 6

    Absolute change in FVC (% pred) from baseline (M0 or inclusion visit) to Month 6 according to the presence of a causal antigen.

    Time frame: at Month 6

  2. The change in FVC (% pred) at 12 months (M12)

    Absolute and relative changes in FVC (% pred) between M0 and M12 will be compared between the placebo arm and the prednisolone arm.

    Time frame: At month 12

  3. The change in FVC (mL) at 12 months (M12)

    Absolute and relative changes in FVC (mL) between M0 and M12 will be compared between the placebo arm and the prednisolone arm.

    Time frame: At month 12

  4. The changes in DLco (mmol/min/kPa) at Month 6

    Time frame: At Month 6

  5. The changes in DLco (% pred) at Month 6

    Time frame: At Month 6

  6. The changes in DLco (mmol/min/kPa) at Month 12

    Time frame: At Month12

  7. The changes in DLco (% pred) at Month 12

    Time frame: At Month 12

  8. The changes in distance walked during six-minute walt test 6MWT in meters (m) at Month 12

    Changes in distance walked during 6MWT (m) from Month 0 to Month12 will be compared between the placebo arm and the prednisolone arm

    Time frame: at Month12

  9. The changes in distance walked during six-minute walt test 6MWT (% pred) at Month 12

    Changes in distance walked during 6MWT (%pred) from Month 0 to Month12 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 12

  10. The changes in distance walked during six-minute walt test 6MWT in meters (m) at Month 6

    Changes in distance walked during 6MWT (m) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 6

  11. The changes in distance walked during six-minute walt test 6MWT (%pred) at Month 6

    Changes in distance walked during 6MWT (%pred) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 6

  12. The change in health related QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ) at Month 6

    Changes in Respiratory QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ)) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 6

  13. The change in health related QoL (King's Brief ILD questionnaire) at Month 6

    Changes in Respiratory QoL (King's Brief ILD questionnaire) from Month 0 to Month 6 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 6

  14. The change in health related QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ) at Month 12

    Changes in Respiratory QoL (the Saint Georges Hospital Respiratory Questionnaire (SGRQ)) from Month 0 to Month 12 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 12

  15. The change in health related QoL (King's Brief ILD questionnaire) at Month 12

    Changes in Respiratory QoL (King's Brief ILD questionnaire) from Month 0 to Month 12 will be compared between the placebo arm and the prednisolone arm

    Time frame: At Month 12

  16. The proportion of patients who develop pulmonary progressive fibrosis (PPF) within 12 months

    Time frame: Over 12 months

  17. The proportion of subjects who experience acute exacerbation (AE) or require unplanned hospitalization within 12 months

    Time frame: Over 12 months

  18. Progression free survival (PFS) at 12 months

    Time frame: At month 12

06

Study locations

No study locations are listed for this record.

07

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07210008
Lead sponsor
Assistance Publique - Hôpitaux de Paris
Responsible party
Sponsor
First posted
Oct 7, 2025
Start date
Jun 1, 2026 (estimated)
Primary completion
Dec 1, 2028 (estimated)
Completion
Dec 1, 2028 (estimated)
Last update
Oct 7, 2025

Study contacts

Lucile SESE
Contact
lucile.sese@aphp.fr
06 67 72 91 03
Hilario NUNES
Contact
hilario.nunes@aphp.fr
01 48 95 51 21
Lucile SESE
study director · Assistance Publique - Hôpitaux de Paris

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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