Efficacy and Safety of Golidocitinib for Rapidly Progressive Interstitial Lung Disease

Official title

A Prospective, Multi-center, Randomized Controlled Clinical Trial to Evaluate the Efficacy and Safety of Golidocitinib in Rapidly Progressive Interstitial Lung Disease

Overview

The goal of this clinical trial is to learn whether adding the JAK inhibitor golidocitinib to standard corticosteroid therapy works to treat rapidly progressive interstitial lung disease (RP-ILD) in patients with acute worsening. It will also learn about its safety compared to standard treatment without JAK inhibitors (i.e., corticosteroids plus other immunosuppressants such as mycophenolate mofetil, tacrolimus, cyclophosphamide, or biologics). The main questions it aims to answer are: * How much does the addition of golidocitinib improve lung function, measured by the absolute change in FVC (mL), after 12 weeks of treatment? * How does it compare to standard therapy in terms of changes in FVC% predicted, oxygenation index, chest CT score, need for invasive respiratory support, all-cause mortality, relapse rate, and incidence of opportunistic infections? Researchers will compare the golidocitinib group (golidocitinib 150 mg once daily plus corticosteroids) to the control group (corticosteroids plus non-JAK inhibitor immunosuppressants). All patients receive high-dose corticosteroids (prednisone equivalent ≥1 mg/kg/day) with a tapering regimen. Participants will: * Receive either golidocitinib plus corticosteroids or control treatment for 12 weeks * Visit the clinic for check-ups, blood tests, and lung function tests at weeks 1, 2, 4, 6-8, and 12 * Have chest high-resolution CT scans at weeks 2, 4-6, and 12 to monitor disease progression * Be monitored for adverse events and efficacy outcomes throughout the 12-week period

Interventions

• Drug golidocitinib plus corticosteroid
  Corticosteroid regimen: Methylprednisolone 80 mg intravenous infusion twice daily for 7 days, then tapered to 40 mg twice daily for 7 days; subsequently, after 7 days of oral full-dose corticosteroids, the tapering begins with a reduction of 2.5 mg per week until the dose reaches 30 mg daily, after which the dose is reduced by 2.5 mg every 2 weeks until 15 mg daily, and then an individualized tapering schedule is applied according to the patient's clinical condition. Concurrently, golidocitinib
• Drug non-JAK inhibitor immunosuppressant plus corticosteroid
  Corticosteroid regimen: Methylprednisolone 80 mg intravenous infusion twice daily for 7 days, then tapered to 40 mg twice daily for 7 days; subsequently, after 7 days of oral full-dose corticosteroids, the tapering begins with a reduction of 2.5 mg per week until the dose reaches 30 mg daily, after which the dose is reduced by 2.5 mg every 2 weeks until 15 mg daily, and then an individualized tapering schedule is applied according to the patient's clinical condition. Non-JAK inhibitor immunosupp

Primary outcome measures

• Rate of change in absolute forced vital capacity (FVC) in milliliters (mL) within 12 weeks [Time frame: Week 12]

Secondary outcome measures (8)

• Absolute change in FVC % predicted within 12 weeks [Time frame: Week 12]
• Percent change in FVC % predicted within 12 weeks [Time frame: Week 12]
• Absolute change in oxygenation index within 12 weeks [Time frame: Week 12]
• Change in chest CT score within 12 weeks [Time frame: Week 12]
• Proportion of patients requiring invasive respiratory support within 12 weeks [Time frame: Week 12]
• All-cause mortality within 12 weeks [Time frame: Week 12]
• Relapse rate within 12 weeks [Time frame: Week 12]
• Incidence of opportunistic infections within 12 weeks [Time frame: Week 12]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Meet the diagnostic criteria for rapidly progressive interstitial lung disease (RP-ILD) and require treatment with corticosteroids and immunosuppressants, defined as: Acute worsening of cough and dyspnea occurring within 1 month; Chest CT showing ILD manifestations with new or worsening exudative lesions (ground-glass opacities and/or consolidation); Presence of respiratory failure (PaO₂ < 60 mmHg at rest without oxygen supplementation, or SpO₂ < 90% on room air), or significant worsening of hypoxemia (a decrease in PaO₂ of ≥ 10 mmHg), or a clear decline in two recent pulmonary function tests: a decrease in FVC % predicted of ≥ 10% and/or a decrease in DLCO % predicted of ≥ 15% accompanied by a decline in FVC; Exclusion of heart failure or fluid overload, pulmonary infectious diseases, and pulmonary embolism
• No prior treatment with JAK inhibitors
• Able to comply with scheduled follow-up visits
• Patient and family members understand the study protocol, are willing to participate, and are able to provide written informed consent.

Exclusion criteria

• The patient or family members are unable to understand the conditions and objectives of this study, or are unable to provide informed consent
• Subjects who are unable to comply with the follow-up schedule as required by the protocol, including those who cannot cooperate with pulmonary function testing
• Presence of other severe diseases that, in the investigator's opinion, may affect patient safety or compliance
• Any significant clinical or laboratory abnormalities that, in the investigator's opinion, may affect the safety evaluation
• Oxygenation index ≤ 100, and/or requirement for invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) support
• Pregnant or lactating women, as well as patients who are unable to use effective contraception during the study period and within 3 months after the end of the study
• Presence of contraindications to golidocitinib administration, including a history of allergy to relevant drugs, or presence of active and uncontrolled infections, such as evidence of HIV, HBV (HBsAg-positive, HBV-DNA-positive or ≥ 1000 copies/mL), HCV (anti-HCV antibody-positive or HCV-RNA-positive), or any symptomatic bacterial, viral, parasitic, or fungal infection requiring treatment
• Need for concomitant use of acetaminophen or propacetamol, or preparations containing these ingredients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union — Beijing

Identifiers

NCT: NCT07737249 · K11031

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗