A Multicenter Trial to Evaluate the Efficacy, Safety and Tolerability of HZN-825 in Subjects With Idiopathic Pulmonary Fibrosis

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a randomized, double-blind, placebo-controlled, repeat-dose, multicenter trial to evaluate the efficacy, safety and tolerability of HZN-825 in subjects with IPF. Subjects will be screened within 8 weeks prior to the Baseline (Day 1) Visit. Approximately 360 subjects who meet the trial eligibility criteria will be randomly assigned in a 1:1:1 ratio on Day 1 to receive HZN-825 300 mg QD, HZN-825 300 mg BID or placebo for 52 weeks using the following 2 stratification factors:

1. Prior use of approved IPF therapy (i.e., nintedanib or pirfenidone): yes or no

2. FVC % predicted at Baseline: ≥70% or <70%

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Horizon Therapeutics Ireland DAC

Criteria

Inclusion Criteria:

1. Written informed consent.

2. Male or female between the ages of 18 and 80 years, inclusive, at Screening.

3. 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., 2018]; the date of diagnosis of IPF should be ≥1 year to ≤7 years prior to Screening.

4. Not currently being treated with specific IPF therapy for the reasons below:

1. intolerant or not responsive to approved IPF therapies

2. ineligible to receive approved IPF therapies

3. declines approved IPF therapies

5. Lung HRCT historically performed within 6 months prior to the Screening Visit and according to the minimum requirements for IPF diagnosis by central review based on subject's HRCT. If an evaluable HRCT is not available within 6 months prior to Screening, an HRCT will be performed at Screening to determine eligibility, according to the same requirements as the historical HRCT.

6. HRCT shows ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing and the extent of fibrotic changes is greater than the extent of emphysema on the most recent HRCT scan (central reviewer determined).

7. Meets all of the following criteria during the Screening Period:

1. FVC ≥45% and ≤80% predicted of normal

2. forced expiratory volume in 1 second (FEV1)/FVC ≥0.7

3. DLCO corrected for hemoglobin is ≥30% and ≤90% predicted of normal

8. Estimated minimum life expectancy of ≥30 months for non-IPF-related disease, in the opinion of the Investigator.

9. Vaccinations are up to date given age, comorbidities (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]), pneumococcal pneumonia, herpes zoster, tetanus) 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

Exclusion Criteria:

1. Any of the following cardiovascular diseases:

1. uncontrolled, severe hypertension (≥160/100 mmHg), within 6 months of Screening

2. myocardial infarction within 6 months of Screening

3. 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 A. Prednisone ≤10 mg/day (or equivalent dosing of glucocorticoids) is allowed. Treatment with any other immunosuppressant during the Screening Period through the end of trial participation will require consultation with and approval by the trial Medical Monitor.

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 1 month after last dose of trial drug. Male subjects must refrain from sperm donation and females from egg/ova donation for this same time period.

9. Pregnant or lactating women and women who plan to become pregnant or breast feed during the trial and within 1 month after the last dose of trial drug.

10. Current drug or alcohol abuse or history of either within the previous 2 years, in the opinion of the Investigator or as reported by the subject.

11. Previous enrollment in this trial or participation in a prior HZN-825 or SAR100842 clinical trial.

12. Known history of positive test for human immunodeficiency virus.

13. Active hepatitis (hepatitis B: positive hepatitis B surface antigen and positive anti-hepatitis B core antibody [anti-HBcAb] and negative hepatitis B surface antibody [HBsAb] or positive for HBcAb with a positive test for HBsAb and with presence of hepatitis B virus DNA at Screening; hepatitis C: positive anti-hepatitis C virus [anti-HCV] and positive RNA HCV).

14. Current alcoholic liver disease, primary biliary cirrhosis or primary sclerosing cholangitis.

15. Previous organ transplant (including allogeneic and autologous marrow transplant).

16. International normalized ratio >2, prolonged prothrombin time >1.5 × the upper limit of normal (ULN) or partial thromboplastin time >1.5 × ULN at Screening.

17. Alanine aminotransferase or aspartate aminotransferase >2.0 × ULN.

18. Estimated glomerular filtration rate <30 mL/min/1.73 m2 at Screening.

19. Total bilirubin >2 × ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is ≤3.0 mg/dL.

20. Moderate (Child-Pugh B) to severe (Child-Pugh C) hepatic impairment according to the Child-Pugh scoring system.

21. Any verified Grade 4 laboratory abnormality.

22. Any acute laboratory abnormality at Screening that, in the opinion of the Investigator, would preclude the subject's participation in the trial.

23. Exposure to an experimental drug (with the exception of HZN-825) or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is the longest, prior to Day 1.

24. Any other condition that, in the opinion of the Investigator, would preclude enrollment in the trial.