A Randomized, Double-blind, Placebo-controlled, Repeat-dose, Multicenter Trial of HZN-825 in Patients with Idiopathic Pulmonary Fibrosis

JRCT ID: jRCT2031220586

Registered date:22/01/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Idiopathic pulmonary fibrosis (IPF)
• Date of first enrollment: 11/01/2023
• Target sample size: 16
• Countries of recruitment: ARGENTINA,Japan,AUSTRALIA,Japan,BELGIUM,Japan,BRAZIL,Japan,CANADA,Japan,COLOMBIA,Japan,FRANCE,Japan,GERMANY,Japan,GREECE,Japan,HUNGARY,Japan,ISRAEL,Japan,ITALY,Japan,KOREA, REPUBLIC OF,Japan,MEXICO,Japan,NEW ZEALAND,Japan,PERU,Japan,POLAND,Japan,SOUTH AFRICA,Japan,SPAIN,Japan,TURKEY,Japan,UNITED KINGDOM,Japan,UNITED STATES,Japan
• Study type: Interventional
• Intervention(s): Administer HZN-825 once daily (QD) or twice daily (BID)

Outcome(s)

• Primary Outcome: Change in FVC % predicted from Baseline to Week 52.

Secondary Outcome

1. Proportion of subjects with decline in FVC % predicted equal to or larger than 10% from Baseline at Week 52.
2. Change from Baseline in the 6MWT results to Week 52.
3. Change from Baseline in K-BILD scores to Week 52.
4. Change from Baseline in L-IPF scores to Week 52.
5. Change from Baseline in LCQ scores to Week 52.
6. Time to first hospitalization due to respiratory distress from Baseline up to Week 52.
7. Time to first onset of the composite endpoint of PFS from Baseline up to Week 52, where progression includes decline in FVC % predicted equal to or larger than 10% or death.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

1. Written informed consent.
2. Male or female between the ages of 18 and 80 years, inclusive, 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 and determined by central review; the date of initial diagnosis of IPF should be equal or more than 1 year to equal or less than 7 years prior to Screening.
4. Not currently being treated with specific IPF therapy for the reasons below:
a. intolerant or not responsive to approved IPF therapies
b. ineligible to receive approved IPF therapies
c. 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 equal or more than 10% to less than 50% parenchymal fibrosis (reticulation) and less than 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:
a. FVC equal or more than 45% and equal or less than 80% predicted of normal
b. forced expiratory volume in 1 second (FEV1)/FVC equal or more than 0.7
c. DLCO corrected for hemoglobin is equal or more than 30% and equal or less than 90% predicted of normal
8. Estimated minimum life expectancy of equal or longer than 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.

Exclude criteria

1. Any of the following cardiovascular diseases:
a. uncontrolled, severe hypertension (equal or more than 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 more than 10 mg/day or equivalent or cyclosporine A. Prednisone equal or less than 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. 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. 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 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 more than 2, prolonged prothrombin time more than 1.5 x the upper limit of normal (ULN) or partial thromboplastin time more than 1.5 x ULN at Screening.
17. Alanine aminotransferase or aspartate aminotransferase more than 2.0 x ULN.
18. Estimated glomerular filtration rate less than 30 mL/min/1.73 m2 at Screening.
19. Total bilirubin more than 2 x ULN. Subjects with documented diagnosis of Gilbert's syndrome may be enrolled if their total bilirubin is equal or less than 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.

Related Information

• Primary Sponsor: Sakanishi Ryuichi