Idiopathic Pulmonary Fibrosis Scarred Lungs
Conditions
Interventions
Core phase: Subjects will take 2 tablets of trial drug orally in the morning
and evening with a meal.
• HZN-825 300 mg QD regimen: 2 HZN-825 tablets in the morning and 2 placebo
tablets in the eveni
Sponsors
Horizon Therapeutics Ireland DAC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Core phase: 1. Written informed consent. 2. Male or female >=18 years of age at Screening. 3. Current diagnosis of IPF, as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) guidelines [Raghu et al., 2022] and determined by central review; the date of initial diagnosis of IPF should be =10% to =45% predicted of normal b. forced expiratory volume in 1 second (FEV1)/FVC >=0.7 c. DLCO corrected for hemoglobin is >=25% and =30 months for non-IPF-related disease, in the opinion of the Investigator. 9. Vaccinations are up to date, according to the Investigator*s discretion, given age, comorbidities and local availability prior to trial drug dosing. 10. Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial. Extension phase: 1. Written informed consent. 2. Completed the Double-blind Treatment Period (Week 52) of the Core Phase of the trial; subjects prematurely discontinued from trial drug in the Core Phase of the trial for
Exclusion criteria
Exclusion criteria: Core phase: 1. Any of the following cardiovascular diseases: a. uncontrolled, severe hypertension (>=160/100 mmHg), within 6 months of Screening b. myocardial infarction within 6 months of Screening c. unstable cardiac angina within 6 months of Screening 2. Interstitial lung disease (ILD) associated with known primary diseases (e.g., sarcoidosis, amyloidosis and coronavirus disease 2019 [COVID-19]), connective tissue disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, Sjogren*s, dermatomyositis, scleroderma), exposures (e.g., radiation, silica, asbestos and coal dust) or drugs (e.g., amiodarone). 3. Known active bacterial, viral, fungal, mycobacterial or other infection, including tuberculosis or atypical mycobacterial disease (fungal infections of nail beds are allowed). The subject must be 3 months beyond any acute infection with COVID-19 if there has been a prior infection. 4. Clinically significant pulmonary hypertension requiring chronic medical therapy. 5. Use of any of the following therapies within 4 weeks prior to Screening, during the Screening Period or planned during the trial: prednisone at steady dose >10 mg/day or equivalent or cyclosporine. Prednisone <=10 mg/day (or equivalent dosing of glucocorticoids) is allowed. Change in regimen or dosage of any immunosuppressant during the Screening Period through the end of trial participation will require consultation with and approval by the trial Medical Monitor. See Section 9.4.9 for full details. Avoiding the use of listed prohibited treatments must not be considered detrimental and must be indicated by the treating physician. Subjects must not be withdrawn from any standard-of-care treatment that is considered necessary for the clinical management of the subject in order to fulfill the trial eligibility requirements. 6. Use of rifampin within 2 weeks prior to Day 1 or planned during the trial. 7. Malignant condition in the past 5 years (except successfully treated basal/squamous cell carcinoma of the skin or cervical cancer in situ). 8. Women of childbearing potential (WOCBP) or male subjects not agreeing to use highly effective method(s) of birth control throughout the trial and for 4 weeks after last dose of trial drug. Females must refrain from egg/ova donation for 4 weeks after the last dose of trial drug and males must refrain from sperm donation for 3 months after the last dose of trial drug. Women are considered of childbearing potential if they are not postmenopausal and not surgically sterile (documented bilateral salpingectomy, bilateral oophorectomy or hysterectomy). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Fertile male subjects must use a condom throughout the trial and for 4 weeks after the last dose of trial drug. A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 9. Pregnant or lactating women and women who plan to become pregnant or breast feed during the trial and withi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Core phase: Change in FVC % predicted from Baseline to Week 52. Extension phase: The primary endpoint is the change from both Baselines in FVC % predicted at Week 104. | — |
Secondary
| Measure | Time frame |
|---|---|
| Core phase: Key secondary efficacy endpoint: Proportion of subjects with decline in FVC % predicted >=10% from Baseline at Week 52. Other secondary efficacy endpoints: 1. Change from Baseline in the 6MWT results to Week 52. 2. Change from Baseline in K-BILD scores to Week 52. 3. Change from Baseline in L-IPF scores to Week 52. 4. Change from Baseline in LCQ scores to Week 52. 5. Time to first hospitalization due to respiratory distress from Baseline up to Week 52. 6. Time to first onset of the composite endpoint of PFS from Baseline up to Week 52, where progression includes decline in FVC % predicted >=10% or death. For exploratory and safety endpoints please refer to the study protocol Extension phase: Safety and tolerability endpoints: • Incidence of TEAEs and the AESI (orthostatic hypotension) in the Extension Phase • Concomitant medication use in the Extension Phase • Change from Trial Baseline in vital signs in the Extension Phase • Change from Trial Baseline in 12-lead ECG measurements in the Extension Phase • Change from Trial Baseline in clinical safety laboratory test results in the Extension Phase For exploratory please refer to the study protocol | — |
Countries
Netherlands
Outcome results
None listed