Randomized, Double‑Blind Trial of Prednisolone Metasulfobenzoate Sodium vs Placebo in Treatment‑Naïve Adults with Fibrotic Hypersensitivity Pneumonitis (RUBY Study)

The primary objective is to evaluate the efficacy of first‑line prednisolone versus placebo on the change in FVC (% predicted) from baseline to six months in patients with fibrotic hypersensitivity pneumonitis, reflecting impact on lung volume preservation. Secondary objectives include:

• Change in FVC (% predicted and mL) at six months according to the presence of a causal antigen.
• Change in FVC (mL) at six months and FVC (% predicted and mL) at twelve months.
• Changes in DLco (mmol/min/kPa and % predicted) and distance walked during the six‑minute walk test (6MWT) in meters and % predicted at six and twelve months.
• Change in health‑related quality of life at six and twelve months.
• Proportion of patients developing pulmonary progressive fibrosis within twelve months.
• Proportion of patients requiring second‑line corticosteroid, immunosuppressive or antifibrotic therapy within twelve months.
• Proportion of subjects experiencing acute exacerbation or unplanned hospitalization within twelve months.
• Assessment of progression free survival at twelve months.
• Evaluation of treatment‑emergent adverse effects.

The trial enrolled adult individuals, both fibrotic Hypersensitivity Pneumonitis patients and healthy controls, aged > 18 years and < 90 years, without restriction by sex. Participants were required to have a definitive or high‑confidence diagnosis of fibrotic HP confirmed by multidisciplinary discussion, a fibrosis extent of ≥ 10 % on chest HRCT, and mild to moderate functional impairment defined by forced vital capacity ≥ 50 % predicted and diffusing capacity for carbon monoxide ≥ 30 % predicted. Additional requirements included written informed consent, affiliation with a social security scheme or CMU, and effective contraception for men and women of child‑bearing potential. Lifestyle factors such as diet, physical activity, or smoking status were not specified. The sponsor did not provide the total number of participants enrolled in the study.

The RUBY study is a phase III, randomized, double-blind, placebo-controlled trial evaluating oral prednisolone 40 mg (SOLUPRED 5 mg orodispersible tablet) versus matching placebo in adult patients with fibrotic hypersensitivity pneumonitis. After an initial screening visit to confirm eligibility, participants attend a baseline (inclusion) visit (M0) where randomisation occurs and baseline assessments—including forced vital capacity (FVC) and diffusing capacity—are performed. Follow‑up visits are scheduled at month 3 (M3), month 6 (M6), and month 12 (M12), during which pulmonary function tests, six‑minute walk distance, respiratory quality‑of‑life questionnaires, and safety evaluations are repeated. The primary efficacy endpoint is the absolute change in FVC % predicted from M0 to M6; secondary endpoints comprise longitudinal changes in FVC and DLco, exercise capacity, quality of life, incidence of progressive fibrotic phenotype, need for second‑line therapy, unplanned hospitalisations, and adverse events. Participant involvement extends for approximately 12 months, concluding with an end‑of‑study visit at M12. Early termination may be triggered by serious adverse events, the requirement for prohibited corticosteroid or immunosuppressive treatment, rapid disease progression meeting predefined criteria, or withdrawal of informed consent.

The investigational product is SOLUPRED 5 mg, an orodispersible tablet containing prednisolone metasulfobenzoate sodium. The tablet is administered orally at a dose of 40 mg per administration, given once daily throughout the treatment period.

The comparator is a matching solupred 5 mg placebo tablet, which contains no active pharmaceutical ingredient. The placebo is supplied in the same dosage form and is taken orally once daily on the same schedule as the active product.

All study medications are dispensed in blister packs to facilitate dosing adherence. Participants receive instructions to ingest the tablet with water; the orodispersible formulation allows dissolution in the oral cavity prior to swallowing. Compliance is monitored by pill count at each study visit, review of patient‑reported dosing diaries, and verification of returned blister packs.

The primary efficacy assessment will compare the absolute change in forced vital capacity (FVC) expressed as percent of predicted value (% pred) from the baseline visit (M0) to month 6 (M6) between participants receiving prednisolone and those receiving placebo.

Secondary efficacy evaluations will include:

• Analysis of the presence of a causal antigen and its impact on the absolute change in FVC (% pred) from M0 to M6.
• Pulmonary function tests (spirometry and diffusing capacity for carbon monoxide, DLco) performed at M0, month 3 (M3), M6, and month 12 (M12); absolute and relative changes in FVC (both mL and % pred) from M0 to M12 and changes in DLco (mmol/min/kPa and % pred) at M0, M6, and M12 will be compared between treatment arms.
• Six‑minute walk test (6MWT) conducted by trained technicians or nurses at M0, M6, and M12; changes in distance walked (meters and % pred) from baseline to M6 and M12 will be compared.
• Respiratory quality of life measured at M0, M6, and M12 using the Saint George’s Respiratory Questionnaire (SGRQ) and King’s Brief Interstitial Lung Disease questionnaire.
• Proportion of patients developing a progressive fibrotic phenotype (PPF) within 12 months, defined according to ATS/ERS/JRS/ALAT guidelines.
• Proportion of patients initiating second‑line therapy (corticosteroids, immunosuppressants, or antifibrotics) within 12 months.
• Proportion experiencing unplanned hospitalization or adverse events as defined by Collard et al. within 12 months.
• Progression‑free survival (PFS), defined by the first occurrence of a relative FVC decline ≥10 % pred, first adverse event, lung transplantation, or death.
• Adverse events recorded using the Common Terminology Criteria for Adverse Events (CTCAE) at M3, M6, and M12, including weight gain, blood pressure changes, and other corticosteroid‑related side effects.

All functional and questionnaire assessments will be performed using validated instruments and standardized protocols at the specified study visits. Data will be analyzed by comparing the mean changes between the prednisolone and placebo arms, with subgroup analyses according to antigen status and disease severity in participants with fibrotic hypersensitivity pneumonitis.