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

NCT ID: NCT07210008

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-06-01
• Study Completion Date: 2028-12-01

Brief 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.

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.

Conditions

Hypersensitivity Pneumonitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

Prednisolone

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Prednisolone

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lucile SESE

Role: STUDY_DIRECTOR

Assistance Publique - Hôpitaux de Paris

Central Contacts

Lucile SESE

Role: CONTACT

lucile.sese@aphp.fr

06 67 72 91 03

Hilario NUNES

Role: CONTACT

hilario.nunes@aphp.fr

01 48 95 51 21

Other Identifiers

2025-521591-64-00

Identifier Type: CTIS

Identifier Source: secondary_id

APHP240908

Identifier Type: -

Identifier Source: org_study_id